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1.
Piglets, separated from their dam at 12 days of age and fed a milk substitute hourly, were used as a model for suckling. Animals were fitted with a terminal ileal T-cannula and a jugular vein catheter. At 28 days of age, half of the pigs had a dietary change to a cereal-based weaner diet fed as slurry, and the others remained on milk substitute. Animals were labelled by oral administration of 15N-labelled yeast for 10 days (days 15 to 25). Blood samples were taken twice a day to monitor 15N enrichment of the blood plasma. Diets included polyethylenglycol (PEG 4000) to allow calculation of apparent ileal digestibility of nitrogen and individual amino acids. Ileal bacterial nitrogen was calculated from D-alanine content of the digesta. Furthermore, small intestinal (SI) villus height and crypt depth were measured. Feed intake was increased by the dietary change. The total nitrogen flow was 3.2 ± 0.4 g/day and 5.9 ± 0.4 for the milk and weaner diet, respectively. Endogenous nitrogen flow at the terminal ileum was similar for both groups (milk diet 2.4 ± 0.4 v. weaner diet 2.2 ± 0.3 g/day), whereas the bacterial nitrogen content (0.08 ± 0.01 g/day milk diet v. 0.15 ± 0.01 g/day weaner diet, P < 0.01) and exogenous nitrogen flow (0.94 ± 0.16 g/day milk diet v. 3.29 ± 0.12 g/day weaner diet, P < 0.001) increased significantly in the weaner-diet group. The ileal apparent digestibility coefficient of protein was 0.81 ± 0.06 and 0.68 ± 0.01 for the milk replacer and the weaner diet, respectively. Morphology measurements made along the SI at 25%, 50% and 75% were similar between piglets fed milk replacer and those fed a cereal-based weaner diet. The only statistical effect (P < 0.01) of dietary change was an increase in crypt depth in the weaner-diet group. In conclusion, pigs, following a dietary change analogous to weaning, lack the capacity to fully digest a standard weaner diet. This may result in an increased nutrient content entering the large intestine and an altered microbiota. In the absence of a period of anorexia, often associated with traditional weaning, we saw no evidence of villous atrophy, but report here a significant crypt hyperplasia, especially at the 75% level, as a result of dietary change.  相似文献   

2.
The response of confluent monolayers of HT29-Cl.16E cells to stimulation by extracellular ATP and ATP analogues was investigated in terms of mucin and electrolyte secretion. Mucin secretion was measured as release of glucosamine-labeled macromolecules trapped at the stacking/running gel interface of polyacrylamide gels and electrolyte secretion as shortcircuit current (Isc). Luminal ATP stimulated a transient increase in the release of mucins and of I sc corresponding to a secretory Cl current. Both secretions peaked at 3 to 5 min after addition of ATP. Maximal ATP-stimulated mucin secretion over 15 min was up to 18-fold above control with an apparent ED50 of approximately 40 m. Maximal peak I sc after stimulation with ATP was approximately 35 A/cm2 with an apparent ED50 of about 0.4 mm. ATP-dependent I sc was at least in part due to Cl secretion since removal of Cl from the medium reduced the peak I sc by 40% and the I sc integrated over 40 min by 80%. The secretory responses were not associated with cell damage as assessed by failure of ethidium bromide to enter into the cells, absence of release of lactate dehydrogenase, maintenance of monolayer conductance, viability, and responses to repeated applications of ATP. The order of efficacy of nucleotide agonists was similar for both processes with ATP>ADP>AMPadenosine. Luminal ATP was much more effective than basolateral addition of this compound. These results suggest involvement of a luminal P2-type receptor which can initiate signaling pathways for granule fusion and mucin release as well as for activation of Cl channels. P2-receptor-stimulated mucin and I sc release was strongly inhibited by a 30 min preincubation with the classical K+ channel blockers quinine (1 mm), quinidine (1 mm), and Ba2+ (3 mm). Experiments with amphotericin B to measure separately the conductance changes of either luminal or basolateral plasma membrane revealed that quinidine did not directly block the ATP-induced basolateral K+ or the luminal anion channels. The quinidine inhibition after preincubation is therefore most easily explained by interference with granule fusion and location of anion channels in granule membranes. Luminal P2 receptors may play a role in intestinal defense mechanisms with both fluid and mucin secretion aiding in the removal of noxious agents from the mucosal surface.Supported by grants from the National Institutes of Health (DK 39658) to U.H., the Philippe Foundation to D.M., the French Cystic Fibrosis Foundation (AFLM) and L'Association Pour La Recherche Sur Le Cancer to C.L. The authors thank Mr. J. Polack for his efforts and skill with electron microscopy and Dr. George Dubyak for helpful discussions. We also acknowledge the Cystic Fibrosis Center Core grant (DK-27651) for its support of electron and light microscopy.  相似文献   

3.
The effect of a dietary phytogenic feed additive (PFA) inclusion level in mucin monosaccharide composition, mucosal morphometry and mucus histochemistry along the broiler intestinal tract was studied. Cobb male broilers (n = 525) were allocated into five experimental treatments that, depending on the type of addition in the basal diet (BD), were labeled as follows: C (BD based on maize–soybean meal with no other additions), E1 (80 mg PFA/kg BD), E2 (125 mg PFA/kg BD), E3 (250 mg PFA/kg of BD) and A (2.5 mg avilamycin/kg BD). Samples from duodenum, ileum and cecum of 14- and 42-day-old broilers were collected and analyzed. In 14-day-old broilers, treatments E2 and E3 had higher (P < 0.01) duodenal mannose than treatments C, E1 and A. Ileal mannose was lower (P < 0.05) in treatment C compared with PFA treatments, and ileal galactose (Gal) was higher (P < 0.01) in treatments E2 and E3 compared with C and A. Polynomial contrast analysis with respect to PFA inclusion level showed that in 14-day-old broilers there was a linear increase (P = 0.001) in duodenal mannose and a quadratic effect (P = 0.038) in duodenal N-acetyl-galactosamine with increasing PFA level. Ileal Gal and mannose increased linearly (P = 0.002 and P = 0.012, respectively) with PFA inclusion level. There were no significant differences between treatments in mucin monosaccharide molar ratios of 42-day-old broilers. However, increasing PFA inclusion level resulted in a linear decrease of ileal fucose (P = 0.021) and cecal N-acetylgalactosamine (P = 0.036). Experimental treatments did not differ (P > 0.05) regarding duodenal villus height (Vh), crypt depth (Cd) and Vh/Cd ratio, irrespective of broiler age and the intestinal segment examined. However, increasing dietary PFA inclusion level showed a pattern of linear increase of duodenal Vh/Cd ratio in 14-day-old broilers and ileal Vh in 42-day-old broilers (P = 0.039 and P = 0.039, respectively). Alcian Blue–Periodic Acid-Schiff (pH 2.5) staining of neutral and acidic mucins showed that the staining intensity of mucus layer in villi was fragment (i.e. tip, midsection and base) dependent, whereas in crypts it was dependent both on intestinal segment (i.e. duodenum, ileum and cecum) and fragment. Finally, mucus layer thickness did not differ (P > 0.05) between treatments, yet a pattern of linear increase (P < 0.05) with PFA inclusion level was observed in the duodenum of 42-day-old broilers. In conclusion, the dietary inclusion level of PFA modulated broiler intestinal mucin composition and morphology. Further studies are required to elucidate the physiological implications of such changes in host–microflora interactions.  相似文献   

4.
The objective of the study was to determine standardized ileal digestibilities (SID) of crude protein (CP) and amino acids (AA) in six ingredients commonly used in weanling pigs diets. The ingredients consisted of extruded soybeans (SBe), high-protein soybean meal (SBMhp), soy protein concentrate (SPC), hydrolyzed wheat gluten (WGh), conventional fish meal 1 (FM1) and extracted fish meal 2 (FM2e). Each assay feed ingredient was added to a purified cornstarch-based basal diet supplemented with casein and crystalline AA, and SID of CP and AA of assay ingredients were estimated using the difference method. A total of 12 3-week-old barrows were surgically fitted with T-cannulas at the distal ileum. The piglets were allocated to four simultaneous 3 × 3 Latin-square designs with three animals and three periods each, resulting in six observations per assay diet. After 3 to 5 days recovery from surgery, each assay diet was fed at a level of 30 g/kg body weight. Each experimental period consisted of 5 days for adaptation to the assay diets and 2 days for ileal digesta collection. The SID of CP, Lys, Met, Thr and Trp were 73%, 78%, 76%, 66% and 71% in SBe; 80%, 84%, 87%, 75% and 81% in SBMhp; 86%, 89%, 89%, 78% and 83% in SPC; 87%, 60%, 88%, 76% and 79% in WGh; 87%, 92%, 94%, 86% and 86% in FM1; and 79%, 86%, 89%, 80% and 74% in FM2e, respectively. The greatest SID of indispensable AA were observed for FM1 and SPC (SID 85% for most indispensable AA), followed by WGh, FM2e and SBMhp (SID 80% for most indispensable AA) and the smallest SID were obtained for SBe (SID < 80% for most indispensable AA). The SID of CP and indispensable AA in both types of fish meal, SBMhp and WGh were similar to SPC (P = 0.063 to 0.855), except for Arg (P = 0.010) and Lys (P = 0.001) in WGh, and Phe (P = 0.044) and Trp (P = 0.037) in FM2e. The SID of CP and indispensable AA were smaller in SBe compared with SPC (P < 0.001 to P = 0.017), except for Lys (P = 0.136). The SID of CP and indispensable AA were consistently smaller in FM2e compared with FM1 with significant differences for CP (P = 0.035), Phe (P = 0.028) and Trp (P = 0.008). Digestibility values measured in the present study can be used to formulate diets for piglets based on standardized ileal digestible contents of CP and AA.  相似文献   

5.
The study was conducted to validate in vitro prediction of standardised ileal digestibilities (SID) of crude protein (CP) and amino acids (AA) in grain legumes for growing pigs using six different cultivars of faba beans (Vicia faba), six different cultivars of field peas (Pisum sativum), and five different cultivars of lupins (Lupinus spp.). The SID for CP and AA were predicted from in vitro analysis by means of a two-step enzymatic method using pepsin and pancreatin incubations. In vitro predicted SID values of CP and AA were generally higher than the corresponding SID values measured in vivo. There were strong linear relationships (r2 = 0.73 for Lys to r2 = 0.91 for Cys and Trp) between in vivo and in vitro predicted SID values in the assay feed ingredients if grain legume species (i.e. faba beans, field peas and lupins) was included as a covariate in multiple linear regression analysis. However, to rapidly and accurately predict SID of CP and AA in individual batches of various feed ingredients, further studies are warranted.  相似文献   

6.
This meta-analysis aimed to estimate the standardized ileal digestibility (SID) and the basal ileal endogenous amino acid losses (IAAend) in barley for growing pigs. In total, 38 different barley treatments published in 26 peer-reviewed papers were used for the meta-analysis containing information on dietary composition including amino acid (AA) contents of the assay diets, and (or) barley samples, as well as apparent ileal digestibility (AID) of AA in barley. The SID of AA was determined by either correcting AID of AA for their IAAend or by regression analysis between the apparent ileal digestible and total dietary AA contents. The SID values obtained by correcting the AID values for their IAAend amounted to 70%, 77%, 74% and 63% for Lys, Met, Thr and Trp, whereas those based on regression analysis method were 82%, 82%, 69% and 55%, respectively. Estimates of basal ileal endogenous loss of CP in ileal digesta varied considerably and averaged 11.84 g/kg dry matter intake (DMI), whereas IAAend for indispensable AA ranged from 0.05 g/kg DMI for Trp to 1.90 g/kg DMI for Leu. In most cases, these estimates were considerably higher than previously reported values for IAAend. The results of the present regression analysis indicate for most AA higher SID values compared with SID of most AA that were obtained by correcting AID values for IAAend. In view of the observed high variations in IAAend and the low CP content of the barley samples, estimating SID of AA based on literature data by means of the regression method may improve accuracy of SID coefficients for barley. In contrast, transformation of AID values into their corresponding SID values by using a constant correction factor for IAAend adds an additional source of error, thereby reducing the precision in estimating SID of AA.  相似文献   

7.
In a double-blind study with six patients, who previously had undergone proctocolectomy for ulcerative colitis, the ileostomy discharge significantly increased from 110 to 295 ml X 4 h-1 during infusion of neurotensin, 3 pmol X kg-1 X min-1 for 4 h. Transit defined as the passage of a perorally ingested unabsorbable marker (polyethylene glycol, PEG 4000) was significantly increased during the last hour of neurotensin infusion. The dose of neurotensin used in this study has previously been shown to result in plasma levels of neurotensin-like immunoreactivity within the range obtained after a fatty meal. Thus, the present data indicate that neurotensin in man may exert a physiological function by increasing net fluid secretion in the small intestine as well as increasing the intestinal transit rate.  相似文献   

8.
Experiments carried out to determine the amino acid requirement in growing animals are often based on the premise that the amino acid composition of body protein is constant. However, there are indications that this assumption may not be correct. The objective of this study was to test the effect of feeding piglets a diet deficient or not in total sulfur amino acids (TSAA; Met + Cys) on nitrogen retention and amino acid composition of proteins in different body compartments. Six blocks of three pigs each were used in a combined comparative slaughter and nitrogen balance study. One piglet in each block was slaughtered at 42 days of age, whereas the other piglets received a diet deficient or not in TSAA for 19 days and were slaughtered thereafter. Two diets were formulated to provide either 0.20% Met and 0.45% TSAA (on a standardized ileal digestible basis) or 0.46% Met and 0.70% TSAA. Diets were offered approximately 25% below ad libitum intake. At slaughter, the whole animal was divided into carcass, blood, intestines, liver, and the combined head, tail, feet and other organs (HFTO), which were analyzed for nitrogen and amino acid contents. Samples of the longissimus muscle (LM) were analyzed for myosin heavy chain (MyHC) and actin contents. Nitrogen retention was 20% lower in piglets receiving the TSAA-deficient diet (P < 0.01). In these piglets, the nitrogen content in tissue gain was lower in the empty body, carcass, LM and blood (P < 0.05) or tended to be lower in HFTO (P < 0.10), but was not different in the intestines and liver. The Met content in retained protein was lower in the empty body, LM and blood (P < 0.05), and tended to be lower in the carcass (P < 0.10). The Cys content was lower in LM, but higher in blood of piglets receiving the TSAA-deficient diet (P < 0.05). Skeletal muscle appeared to be affected most by the TSAA deficiency. In LM, the Met content in retained protein was reduced by 12% and total Met retention by more than 60%. The MyHC and actin contents in LM were not affected by the TSAA content of the diet. These results show that a deficient TSAA supply affects the amino acid composition of different body proteins. This questions the use of a constant ideal amino acid profile to express dietary amino acid requirements, but also illustrates the plasticity of the animal to cope with nutritional challenges.  相似文献   

9.
Excitatory amino acids (EAAs), in particular,L-aspartate (L-Asp) neurons and their processes, were localized in the rat stomach using a immunohistochemical method with specific antibodies against eitherL-Asp or its synthesizing enzyme, aspartate aminotransferase (AAT). Myenteric ganglia and nerve bundles in the circular muscle and in the longitudinal muscle were found to be AAT-orL-Asp-positive. In addition, AAT- orL-Asp-positive cells were also found in the muscle layer and the deep mucosal layer. The distribution of AAT- orL-Asp-positive cells in both the mucosal and muscle layers was heterogeneous in the stomach. In addition,L-Asp at 10–6 M negligibly influenced acid secretion in an everted preparation of isolated rat stomach. However, according to our results,L-Asp markedly inhibited the histamine-stimulated acid secretion, but not the oxotremorine- or the pentagastrin-stimulated acid secretion. Furthermore,L-Asp also inhibited histamine-induced elevation of cAMP.L-Asp itself did not affect the cAMP level although it elevated the cGMP level in the stomach. Moreover, either (+)2-amino-5-phosphonovaleric acid or (±)3-(2-carboxy-piperazin-4-yl)prophyl-1-phosphonic acid, i.e. two specific antagonists for N-methyl-D-aspartic acid (NMDA) receptors, blocked the inhibitory effect ofL-Asp on histamine-stimulated acid secretion or histamine-induced elevation of cAMP. Since cAMP has been strongly implicated as the second messenger involved in histamine-induced acid secretion, we believe thatL-Asp regulates acid secretion in the stomach by inhibiting histamine release through the NMDA receptors, subsequently lowering the level of cAMP and ultimately reducing acid secretion.  相似文献   

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Several models of erosive peptic disease have used drug-induced lesions to examine protective mechanisms of the gastric mucosa. Physiological processes such as acid secretion, motility, or epithelial cell turnover have circadian rhythms which may modulate the susceptibility of the gastric mucosa to injury. In this review are described recent studies which demonstrated that susceptibility to gastric mucosal injury by acidified aspirin and absolute ethanol varied with the phases of the light-dark cycle. Acidified aspirin caused significantly more gastric mucosal lesions when administered early in the light phase compared to administration early in the dark phase. The differences in susceptibility were not altered by pretreatment conditions such as immobilization or length of the fasting period. Absolute ethanol also caused significantly greater gastric mucosal injury when administered in the light than in the dark phase, but this difference was only evident in rats immobilized during the pretreatment fasting period. Further studies are needed to correlate circadian susceptibility to drug-induced gastric mucosal injury with physiological defense mechanisms. Careful attention to circadian timekeeping may allow us to refine therapy to optimize physiological defense mechanisms in the stomach.  相似文献   

13.
Bile acids are generated in vivo from cholesterol in the liver, and they undergo an enterohepatic circulation involving the small intestine, liver, and kidney. To understand the molecular mechanism of this transportation, it is essential to gain insight into the three-dimensional (3D) structures of proteins involved in the bile acid recycling in free and complexed form and to compare them with homologous members of this protein family. Here we report the solution structure of the human ileal lipid-binding protein (ILBP) in free form and in complex with cholyltaurine. Both structures are compared with a previously published structure of the porcine ILBP-cholylglycine complex and with related lipid-binding proteins. Protein structures were determined in solution by using two-dimensional (2D)- and 3D-homo and heteronuclear NMR techniques, leading to an almost complete resonance assignment and a significant number of distance constraints for distance geometry and restrained molecular dynamics simulations. The identification of several intermolecular distance constraints unambiguously determines the cholyltaurine-binding site. The bile acid is deeply buried within ILBP with its flexible side-chain situated close to the fatty acid portal as entry region into the inner ILBP core. This binding mode differs significantly from the orientation of cholylglycine in porcine ILBP. A detailed analysis using the GRID/CPCA strategy reveals differences in favorable interactions between protein-binding sites and potential ligands. This characterization will allow for the rational design of potential inhibitors for this relevant system.  相似文献   

14.
Several models of erosive peptic disease have used drug-induced lesions to examine protective mechanisms of the gastric mucosa. Physiological processes such as acid secretion, motility, or epithelial cell turnover have circadian rhythms which may modulate the susceptibility of the gastric mucosa to injury. In this review are described recent studies which demonstrated that susceptibility to gastric mucosal injury by acidified aspirin and absolute ethanol varied with the phases of the light-dark cycle. Acidified aspirin caused significantly more gastric mucosal lesions when administered early in the light phase compared to administration early in the dark phase. The differences in susceptibility were not altered by pretreatment conditions such as immobilization or length of the fasting period. Absolute ethanol also caused significantly greater gastric mucosal injury when administered in the light than in the dark phase, but this difference was only evident in rats immobilized during the pretreatment fasting period. Further studies are needed to correlate circadian susceptibility to drug-induced gastric mucosal injury with physiological defense mechanisms. Careful attention to circadian timekeeping may allow us to refine therapy to optimize physiological defense mechanisms in the stomach.  相似文献   

15.
Summary Biosynthetic human epidermal growth factor (Bh-EGF) induced dose-dependent synthesis and secretion of neutral mucin glycoprotein when the fundal cells isolated from rabbit stomach were cultured in serum-free medium containing Bh-EGF at concentrations as high as 10 to 100 ng/ml. At these high concentrations, Bh-EGF had no effect on the cell growth. In marked contrast, much lower concentrations from 0.1 to 1.0 ng/ml of Bh-EGF failed to stimulate mucin synthesis, but enhanced proliferation of the cells. Electrophoretic pattern of the mucin secreted from the cultured mucosal cells was very similar to that of the authentic mucin obtained from rabbit stomach. Maximal secretion of the mucin from the cells was observed at Hour 96 of the culture. Although fetal bovine serum (5%) and insulin (0.5 μg/ml) also stimulated the mucosal cells, both in growth and in mucin synthesis and release, the enhancing activity of the mucin synthesized and released by Bh-EGF at a concentration of 100 ng/ml per microgram DNA of cultured cells was far superior to that of 5% fetal bovine serum and 0.5 μg/ml insulin.  相似文献   

16.
Studies were conducted to determine whether β-adrenergic cell signalling is altered in submandibular salivary glands (SMSG) is essential fatty acid (EFA) deficiency. Three groups of rats were fed diets which were deficient in EFA (EFAD), marginally deficient in EFA (MEFAD) or contained sufficient amount of EFA (Control). Rats were killed after 20 wk on diets, SMSG were dissected out and cyclic AMP-dependent protein kinase (PKA) activity was measured. The specific enzyme activities were higher in the homogenates and supernatant fractions of the gland from EFAD and MEFAD rats compared with the controls. The relative levels of guanine nucleotide-binding regulatory proteins (Gs and Gi) were also measured in the SMSG membranes of rats fed the 3 diets. The levels of Gs were significantly higher in the EFAD and MEFAD groups than in the controls. No significant differences were observed in the secretion of trichloroacetic acid-phosphotungstic acid (TCA-PTA) precipitable glycoproteins from the SMSG slices among the 3 dietary groups.  相似文献   

17.
Grains rich in starch constitute the primary source of energy for both pigs and humans, but there is incomplete understanding of physiological mechanisms that determine the extent of digestion of grain starch in monogastric animals including pigs and humans. Slow digestion of starch to produce glucose in the small intestine (SI) leads to undigested starch escaping to the large intestine where it is fermented to produce short-chain fatty acids. Glucose generated from starch provides more energy than short-chain fatty acids for normal metabolism and growth in monogastrics. While incomplete digestion of starch leads to underutilised feed in pigs and economic losses, it is desirable in human nutrition to maintain consistent body weight in adults. Undigested nutrients reaching the ileum may trigger the ileal brake, and fermentation of undigested nutrients or fibre in the large intestine triggers the colonic brake. These intestinal brakes reduce the passage rate in an attempt to maximise nutrient utilisation, and lead to increased satiety that may reduce feed intake. The three physiological mechanisms that control grain digestion and feed intake are: (1) gastric emptying rate; (2) interplay of grain digestion and passage rate in the SI controlling the activation of the ileal brake; and (3) fermentation of undigested nutrients or fibre in the large intestine activating the colonic brake. Fibre plays an important role in influencing these mechanisms and the extent of their effects. In this review, an account of the physiological mechanisms controlling the passage rate, feed intake and enzymatic digestion of grains is presented: (1) to evaluate the merits of recently developed methods of grain/starch digestion for application purposes; and (2) to identify opportunities for future research to advance our understanding of how the combination of controlled grain digestion and fibre content can be manipulated to physiologically influence satiety and food intake.  相似文献   

18.
The aim was to determine the effect of orally administered ovine serum immunoglobulin (Ig) on growth performance, organ weight, gut morphology and mucin production in the Salmonella enteritidis--gavaged growing rat. Four groups consisted of non-gavaged rats fed a casein-based control basal diet (BD) and three groups of rats gavaged with 1×10(7) CFU S. enteritidis and fed a casein-based diet, a diet containing freeze-dried ovine Ig (FDOI) or a casein-based diet containing inactivated ovine Ig (IOI). The rats were randomly allocated to one of the four groups (n=15/group) and received their respective diets for an 18-day experimental study. Gavaging took place on day 15. Average daily gain and body gain : feed ratio (post-gavage, 3 days) were significantly (P<0.05) higher for the Salmonella-challenged rats fed the FDOI diet compared to those fed the BD and IOI diets. At the end of the study, the small intestine and colon were significantly (P<0.05) heavier for the gavaged rats fed the FDOI diet compared to the gavaged rats fed either the BD or IOI diet. Moreover, the relative weights of the caecum, liver and spleen of the gavaged rats fed the BD or IOI diet were significantly (P<0.05) heavier compared to the gavaged rats fed the FDOI diet. Generally, the gavaged rats fed the FDOI diet had significantly (P<0.05) higher goblet cell counts and luminal mucin protein contents than the gavaged rats fed either the BD or IOI diet and had a more functional gut morphology. Overall, the FDOI fraction prevented the acute effects of S. enteritidis.  相似文献   

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