首页 | 本学科首页   官方微博 | 高级检索  
相似文献
 共查询到20条相似文献,搜索用时 803 毫秒
1.
Malonyl-CoA acutely regulates fatty acid oxidation in liver in vivo by inhibiting carnitine palmitoyltransferase. Thus rapid increases in the concentration of malonyl-CoA, accompanied by decreases in long-chain fatty acyl carnitine (LCFA-carnitine) and fatty acid oxidation have been observed in liver of fasted-refed rats. It is less clear that it plays a similar role in skeletal muscle. To examine this question, whole body respiratory quotients (RQ) and the concentrations of malonyl-CoA and LCFA-carnitine in muscle were determined in 48-h-starved rats before and at various times after refeeding. RQ values were 0.82 at baseline and increased to 0.93, 1. 0, 1.05, and 1.09 after 1, 3, 12, and 18 h of refeeding, respectively, suggesting inhibition of fat oxidation in all tissues. The increases in RQ at each time point correlated closely (r = 0.98) with increases (50-250%) in the concentration of malonyl-CoA in soleus and gastrocnemius muscles and decreases in plasma FFA and muscle LCFA-carnitine levels. Similar changes in malonyl-CoA and LCFA-carnitine were observed in liver. The increases in malonyl-CoA in muscle during refeeding were not associated with increases in the assayable activity of acetyl-CoA carboxylase (ACC) or decreases in the activity of malonyl-CoA decarboxylase (MCD). The results suggest that, during refeeding after a fast, decreases in fatty acid oxidation occur rapidly in muscle and are attributable both to decreases in plasma FFA and increases in the concentration of malonyl-CoA. They also suggest that the increase in malonyl-CoA in this situation is not due to changes in the assayable activity of either ACC or MCD or an increase in the cytosolic concentration of citrate.  相似文献   

2.
The flow rate of serum free fatty acids (FFA) into the lipids of brown adipose tissue (BAT) of newborn rabbits was determined by intravenous injection of [14C]-1-palmitate. For a normal 7 day old animal during acute cold exposure the flow rate is (1 hour in 20 degrees C ambient temperature) 0.209 mumol/minute, that is 3.6% of the serum FFA turnover. Prolonged cold exposure only induced an increase in FFA influx if the lipid depot had been depleted (48 hours starvation in 20 degrees C). Consequently, the BAT takes up serum FFA for heat production only after mobilisation of its lipid stores. It is supposed that the mechanism of the uptake of serum FFA by the BAT is connected with their esterification to triglycerides. The phospholipids of BAT which are not only membrane bound lipids are characterized by a high metabolism.  相似文献   

3.
Abstract: Within the first few hours of life in the mouse, marked changes were seen in brain endogenous free fatty acids (FFA). A 21% decrease in the total FFA pool occurred during the 1st h of life, and a constant value was maintained thereafter to 10 h. Polyunsaturated fatty acids displayed a different pattern of change. There was 27% less free ararhidonic acid at birth (0 h) than 1 h later. Similar values were obtained for docosahexaenoic acid at birth and at 10 h, although palmitoleic and oleic acids decreased markedly after 1 h. The polyunsaturated fatty acyl chains of diglycerides (DG) showed a statistically significant increase as a function of time after birth, despite an unchanged total DG pool size. The brains of pups subjected to 40 min of N2-anoxia immediately after delivery exhibited a decrease in FFA, especially the monoenoic components, but 60 min of anoxia yielded higher FFA levels. Anoxia induced at 10 h increased FFA and arachidonic acid was higher than when anoxia was induced at 0 h. FFA accumulation was further stimulated by raising the environmental temperature during anoxia. When anoxia was induced, DG exhibited a net increase in palmitate, oleate, and palmitoleate at 0 and 10 h. No arachidonoyl-DG accumulated at 0 h, even after 60 min of anoxia, and stearate was unchanged at 0 and 10 h. The lipid changes observed in the brain during the first hours of life suggest that the enzymatic reactions that promote accumulation of free arachidonic and docosahexaenoic acids and arachidonoyl-DG in the mature brain are present at low levels at the time of delivery. The sluggish modifications found in our study may be related to the longer resistance of newborns to oxygen deficiency.  相似文献   

4.
We used a new tracer technique, direct tracer injection of [1-14C]palmitate-serum albumin into extracellular fluid (ECF) of epididymal fat pads, to study relative transport rates of ECF-free fatty acids (FFA) to cell-FFA and subsequent esterification to diglyceride fatty acid (DGFA) and triglyceride fatty acid (TGFA) in adipose tissue versus movement of ECF- and cell-FFA into the circulation of mice fed ad libitum or fasted 48 hr. Radioactivity was measured in the following fractions at varying times (for 1 hr): ECF-FFA, cell-FFA, cell-DGFA, cell-TGFA, plasma-FFA (total lipids), and breath CO2. Pool sizes of ECF-FFA, cell-FFA, cell-TGFA, and plasma-FFA were determined. Analysis by multicompartmental methods (SAAM) indicates that the ECF-FFA compartment of epididymal fat pads is in a relatively rapid exchange with a cellular-FFA compartment, but neither is in direct, nor appreciably rapid, communication with circulating FFA. FFA is rapidly esterified in adipocytes of fed mice, but esterification is significantly inhibited in mice fasted for 48 hr. In both dietary states, essentially all labeled FFA appearing in the circulation was derived from ECF-FFA that were first transferred to the cell, esterified to TGFA, then hydrolyzed to FFA before being transported to the circulation.  相似文献   

5.
The mode of free fatty acid (FFA) release from rat brain cortex was examined under various treatments prior to decapitation and at various times after decapitation. Brain FFA are comprised mainly of 16:0, 18:0, 18:1 and 20:4 with smaller amounts of 18:2, 22:4 and 22:6. A biphasic mode of FFA release is observed with respect to post-decapitative ischemic treatment. The initial rapid phase involves a 3-fold increase in 18:0 and 20:4 and this process occurs within the first min of decapitation. The second phase involves a less rapid increase of most fatty acids between 2 and 5 min after decapitation. Besides the ischemia-induced increase in brain FFA, the levels of individual fatty acids are also affected by factors such as handling stress and administration of anesthetic agents. Pentobarbital anesthesia, but not ketamine, caused a partial reduction in 18:0 and 20:4 levels in brain in vivo. Pentobarbital treatment also reduced the rapid phase of FFA increase commencing after decapitation. On the other hand, FFA level was higher in animals subjected to ketamine anesthesia, both during the non-ischemic and ischemic phase. Results obtained from this study indicate that the FFA pool in brain is regulated by a complex mechanism contributed by extrinsic and intrinsic factors.  相似文献   

6.
The mitochondrial pyruvate dehydrogenase complex (PDC) is inactivated in many tissues during starvation and diabetes. We investigated carbohydrate oxidation (CHO) and the regulation of the PDC in lean and obese Zucker diabetic fatty (ZDF) rats during fed and starved conditions as well as during an oral glucose load without and with pharmacologically reduced levels of free fatty acids (FFA) to estimate the relative contribution of FFA on glucose tolerance, CHO, and PDC activity. The increase in total PDC activity (20-45%) was paralleled by increased protein levels ( approximately 2-fold) of PDC subunits in liver and muscle of obese ZDF rats. Pyruvate dehydrogenase kinase-4 (PDK4) protein levels were higher in obese rats, and consequently PDC activity was reduced. Although PDK4 protein levels were rapidly downregulated (57-62%) in both lean and obese animals within 2 h after glucose challenge, CHO over 3 h as well as the peak of PDC activity (1 h after glucose load) in liver and muscle were significantly lower in obese rats compared with lean rats. Similar differences were obtained with pharmacologically suppressed FFA by nicotinic acid, but with significantly improved glucose tolerance in obese rats, as well as increased CHO and delta increases in PDC activity (0-60 min) both in muscle and liver. These results demonstrated the suppressive role of FFA acids on the measured parameters. Furthermore, the results clearly demonstrate a rapid reactivation of PDC in liver and muscle of lean and obese rats after a glucose load and show that PDC activity is significantly lower in obese ZDF rats.  相似文献   

7.
In experiments on Wistar strain rats of both sexes, aged 5, 10 and 14 days and adult (90-120 days), of their own breed, the authors determined the quantitative proportion of individual fatty acids in the serum free non-esterified fatty acid (FFA) fraction, using mixed blood (obtained by decapitation) and the titration method of Trout et al. (1960). The proportion of the individual fatty acids was then determined in this fraction by gas chromatography (Base 1978) and their concentration (in mumol.1-1) was determined by simple calculation from the relative chromatogram data. Animals in the first three age groups were killed in the morning, directly from the nest; in adult rats the FFA fraction was measured after a 20 h fast. It was demonstrated that the increase in the proportion of monoenoic acids was highly statistically significant (about fivefold) during ontogenesis and that there was also a marked increase in the quantitative expression of polyenic acids, especially in group (n-6). The n-6/n-3 acid index in the FFA fraction altered during maturation (despite some fluctuation it basically rose from 4.3 in 5-day-old young to 10.0 in adult rats). It was further demonstrated that the concentration of fatty acids with a very short chain fell significantly during development, so that C 8:0, for example, could be detected only in the first two age groups, but not in 14-day-old and adult rats. The concentration of the saturated fatty acids C 15:0 to C 18:0 in the serum FFA fraction showed a statistically significant increase, while the index expressing the ratio of saturated to unsaturated fatty acids displayed a downward trend during development.  相似文献   

8.
Four groups of rats were subjected to the following conditions: (1) 48 h fasting, (2) 48 h of 4 degrees C cold exposure, (3) 5 h treadmill running, (4) 48 h fasting with 4 degrees C cold exposure. The groups were compared to fed control rats in order to study hormonal and metabolic responses in blood and tissue samples. Isolated hepatocytes were used to evaluate the rate of ketogenesis. Decreases in liver glycogen and increases in blood free fatty acids (FFA) confirmed that glycogenolysis and lipolysis occur in these situations of metabolic stress. Increases in the glucagon/insulin plasma ratio were also noted. Plasma catecholamine levels were only enhanced after running and after cold exposure. Production of blood ketone bodies was stimulated more by running and by fasting than by cold exposure. The low ketone body production observed after cold exposure seems to be linked to increases liver glycogen levels and decreased FFA availability. Liver cells isolated after cold exposure exhibited higher ketogenesis than these isolated after running. This difference in ketogenic capacity could result both from the longer hormonal stimulation by high glucagon/insulin plasma ratios and from the metabolic state of the liver.  相似文献   

9.
The aim of this study was to investigate the effects of seasonal variation and fasting on fat reserves of the common vampire bat Desmodus rotundus. Plasma free fatty acids (FFA), along with lipid content of the liver and muscles, and fatty acids from the carcass were obtained from bats fed bovine blood and from whom food was subsequently withheld for 24 and 48 h. Animals were caught during both dry and rainy seasons. In general, fat tissue stores were not significantly influenced by seasonal variation. Lipid content of liver, muscles, and carcass decreased during some food deprivation periods, although the concomitant increase expected in plasma FFA was not observed. Lipid metabolism is hypothesized as being continued by the tissues themselves. In addition, free access to food sources (e.g., domestic livestock) throughout the year is believed to contribute to the low seasonal variations in fat reserves observed in the common vampire bat.  相似文献   

10.
AMPK plays a central role in influencing fuel usage and selection. The aim of this study was to analyze the impact of low-dose AMP analog 5-aminoimidazole-4-carboxamide-1-beta-d-ribosyl monophosphate (ZMP) on whole body glucose turnover and skeletal muscle (SkM) glucose metabolism. Dogs were restudied after prior 48-h fatty acid oxidation (FA(OX)) blockade by methylpalmoxirate (MP; 5 x 12 hourly 10 mg/kg doses). During the basal equilibrium period (0-150 min), fasting dogs (n = 8) were infused with [3-(3)H]glucose followed by either 2-h saline or AICAR (1.5-2.0 mg x kg(-1) x min(-1)) infusions. SkM was biopsied at completion of each study. On a separate day, the same protocol was undertaken after 48-h in vivo FA(OX) blockade. The AICAR and AICAR + MP studies were repeated in three chronic alloxan-diabetic dogs. AICAR produced a transient fall in plasma glucose and increase in insulin and a small decline in free fatty acid (FFA). Parallel increases in hepatic glucose production (HGP), glucose disappearance (R(d tissue)), and glycolytic flux (GF) occurred, whereas metabolic clearance rate of glucose (MCR(g)) did not change significantly. Intracellular SkM glucose, glucose 6-phosphate, and glycogen were unchanged. Acetyl-CoA carboxylase (ACC approximately pSer(221)) increased by 50%. In the AICAR + MP studies, the metabolic responses were modified: the glucose was lower over 120 min, only minor changes occurred with insulin and FFA, and HGP and R(d tissue) responses were markedly attenuated, but MCR(g) and GF increased significantly. SkM substrates were unchanged, but ACC approximately pSer(221) rose by 80%. Thus low-dose AICAR leads to increases in HGP and SkM glucose uptake, which are modified by prior FA(ox) blockade.  相似文献   

11.
Objective: It has been hypothesized that excessive fatty acid availability contributes to steatosis and the metabolic abnormalities associated with nonalcoholic fatty liver disease (NAFLD). The purpose of this study was to evaluate whether adipose tissue lipolytic activity and the rate of fatty acid release into plasma are increased in obese adolescents with NAFLD. Methods: Palmitate kinetics were determined in obese adolescents with normal (n = 9; BMI = 37 ± 2 kg/m2; intrahepatic triglyceride (IHTG) ≤5.5% of liver volume) and increased (n = 9; BMI = 36 ± 2 kg/m2; IHTG ≥ 10% of liver volume) IHTG content during the basal state (postabsorptive condition) and during physiological hyperinsulinemia (postprandial condition). Both groups were matched on body weight, BMI, percent body fat, age, sex, and Tanner stage. The hyperinsulinemic‐euglycemic clamp procedure, in conjunction with a deuterated palmitate tracer infusion, was used to determine free‐fatty acid (FFA) kinetics, and magnetic resonance spectroscopy was used to determine IHTG content. Results: The rate of whole‐body palmitate release into plasma was greater in subjects with NAFLD than those with normal IHTG content during basal conditions, (87 ± 7 vs. 127 ± 13 µmol/min; P < 0.01) and during physiological hyperinsulinemia, (24 ± 2 vs. 44 ± 8 µmol/min; P < 0.01). Discussion: These results demonstrate that adipose tissue lipolytic activity is increased in obese adolescents with NAFLD and results in an increase in the rate of fatty acid release into plasma throughout the day. This continual excess in fatty acid flux supports the hypothesis that adipose insulin resistance is involved in the pathogenesis of steatosis and contributes to the metabolic complications associated with NAFLD.  相似文献   

12.
The effect of arginine vasotocin (AVT) on free fatty acid (FFA) release from pigeon adipose tissue slices incubated in vitro was studied. AVT at concentrations of 0.5 microgram/ml and 5.0 micrograms/ml was found to produce significant increases in the release of FFA from the adipose tissue. This augmentation of FFA release did not require the presence of hydrocortisone.  相似文献   

13.
Following the administration of clofibrate to rats, the concentration of Z protein or fatty acid binding protein in liver cytosol increases by 98 %. Ligandin concentration remains unchanged. Isolated perfused livers of clofibrate-treated rats take up free fatty acids from the perfusate at a significantly higher rate (+ 76 %) than controls. Lipid synthesis from radioactive fatty acids is not modified by clofibrate administration. The yield of plasma membranes obtained from liver homogenates as well as their lipid composition are similar in control and clofibrate treated livers. These results seem to exclude the possibility that the enhancement of FFA uptake could result from an indirect effect of the drug on FFA metabolism and/or plasma membrane surface and thus support the view that Z protein plays a role in intracellular fatty acid transport in the liver.  相似文献   

14.
The present study was designed to investigate the presence of the fatty acid-binding protein (FABPPM) in the plasma membranes of skeletal muscles with different oxidative capacities for free fatty acid (FFA) oxidation during conditions of normal (fed) or increased (fasted) FFA utilization in the rat. Female Sprague-Dawley rats were either fed or fasted for 12, 24, or 48 h and, plasma membranes (PM) fractions from red and white skeletal muscles were isolated. Short-term fasting significantly decreased body weight by 11% and blood glucose concentration by 42% (6.6 ± 0.2-3.8 ± 0.4 mmol/l) and increased plasma FFA concentration by 5-fold (133 ± 14-793 ± 81 µmol/l). Immunoblotting of PM fractions showed that FABPPM protein content was 83 ± 18% higher in red than in white skeletal muscle and correlated with oxidative capacity as measured by succinate dehydrogenase activity (r = 0.78, p < 0.05). Short-term fasting significantly increased FABPPM protein content by 60 ± 8% in red skeletal muscle but no change was measured in white skeletal muscle. These results show that FABPPM protein content in skeletal muscle is related to oxidative potential and can be increased during a physiological condition known to be associated with an increase in FFA utilization, suggesting that cellular expression of FABPPM may play a role in the regulation of FFA metabolism in skeletal muscle. (Mol Cell Biochem 166: 153-158, 1997)  相似文献   

15.
In hypoxic or ischemic states the release of fatty acids is proposed to have several harmful effects on brain structure and function. We therefore decided to study brain FFA in a simple, clinically related animal model resembling intrauterine perinatal asphyxia (PA). Cerebral blood flow (CBF), brain fatty acids (C14:0, C16:1, C16:0, C18:1, C1 8:0, sigma C), plasma glucose, lactate, beta-hydroxybutyrate (beta-OHB), non-esterified fatty acids (NEFA) and insulin were determined in PA and compared to the normoxic state. Brain C 14:0 FFA were not significantly different from normoxic rats. Brain FFA C 16:0 were comparable between groups but significantly decreased at 20 min of PA. C 18:0 FFA showed a trend to increase with the length of PA reaching significance at 10 min of asphyxia only and were declining at 20 min, however, not significantly. Brain C 16:1 and C 18:1 FFA concentrations were comparable between groups. The parameters cerebral blood flow, glucose and lactate showed a stepwise and significant increase with the length of PA, whereas beta-HOB, NEFA and insulin showed no changes. CBF, glucose and lactate showed a strong association whereas other parameters failed to correlate with each other. Only inconsistent trends of increased brain FFA were found and the association between brain glucose and brain FFA could be ruled out. Although CBF was manifold and significantly elevated in PA, brain FFA pattern suggests that the increase of CBF is obviously not mediated by brain FFA. We conclude that FFA may not be involved in the early phase-pathogenesis of PA.  相似文献   

16.
These studies were conducted to assess the relationship between visceral adipose tissue free fatty acid (FFA) release and splanchnic FFA release. Steady-state splanchnic bed palmitate ([9,10-(3)H]palmitate) kinetics were determined from 14 sampling intervals from eight dogs with chronic indwelling arterial, portal vein, and hepatic vein catheters. We tested a model designed to predict the proportion of FFAs delivered to the liver from visceral fat by use of hepatic vein data. The model predicted that 15 +/- 2% of hepatic palmitate delivery originated from visceral lipolysis, which was greater (P = 0.004) than the 11 +/- 2% actually observed. There was a good relationship (r(2) = 0.63) between the predicted and observed hepatic palmitate delivery values, but the model overestimated visceral FFA release more at lower than at higher palmitate concentrations. The discrepancy could be due to differential uptake of FFAs arriving from the arterial vs. the portal vein or to release of FFAs in the hepatic circulatory bed. Splanchnic FFA release measured using hepatic vein samples was strongly related to visceral adipose tissue FFA release into the portal vein. This finding suggests that splanchnic FFA release is a good indicator of visceral adipose tissue lipolysis.  相似文献   

17.
Lipoprotein lipase (LPL) releases fatty acids from triglyceride-rich lipoproteins for use in cellular metabolic reactions. How this hydrolysis, which occurs at the vascular endothelium, is regulated is poorly understood. A fatty acid feedback system has been proposed by which accumulation of fatty acids impedes LPL-catalyzed hydrolysis and dissociates the enzyme from its endothelial binding sites. We examined this hypothesis in humans who were subjected to an oral fat tolerance test of a mixed-meal type. Plasma triglycerides, free fatty acids, and LPL activity were measured before and repeatedly during a 12-h period after intake of the fat load. Since soybean oil with a high content of linoleic fatty acid was the source of triglycerides, a distinction could be made between endogenous free fatty acids (FFA) and FFA derived directly from lipolysis of postprandial triglyceride-rich lipoproteins. Mean LPL activity was almost doubled (P less than 0.01) 6 h after intake of the oral fat load. The rise in LPL activity was accompanied by an increase of plasma triglycerides and linoleic free fatty acids (18:2 FFA), but not of total plasma FFA, which instead displayed a heterogeneous pattern with essentially unchanged mean levels. The postprandial response of LPL activity largely paralleled the postprandial responses of 18:2 FFA and triglycerides. The highest degree of parallelism was seen between postprandial 18:2 FFA and LPL activity levels. Furthermore, the integrated response (area under the curve, AUC) for plasma measurements of LPL correlated with the AUC for 18:2 FFA (r = 0.40, P less than 0.05), but not with the AUC for plasma triglycerides (r = 0.21, ns). The high degree of parallelism and significant correlation between postprandial plasma LPL activity and 18:2 FFA support the hypothesis of fatty acid control of endothelial LPL during physiological conditions in humans.  相似文献   

18.
To investigate the sites of the free fatty acid (FFA) effects to increase basal hepatic glucose production and to impair hepatic insulin action, we performed 2-h and 7-h Intralipid + heparin (IH) and saline infusions in the basal fasting state and during hyperinsulinemic clamps in overnight-fasted rats. We measured endogenous glucose production (EGP), total glucose output (TGO, the flux through glucose-6-phosphatase), glucose cycling (GC, index of flux through glucokinase = TGO - EGP), hepatic glucose 6-phosphate (G-6-P) content, and hepatic glucose-6-phosphatase and glucokinase activities. Plasma FFA levels were elevated about threefold by IH. In the basal state, IH increased TGO, in vivo glucose-6-phosphatase activity (TGO/G-6-P), and EGP (P < 0.001). During the clamp compared with the basal experiments, 2-h insulin infusion increased GC and in vivo glucokinase activity (GC/TGO; P < 0.05) and suppressed EGP (P < 0.05) but failed to significantly affect TGO and in vivo glucose-6-phosphatase activity. IH decreased the ability of insulin to increase GC and in vivo glucokinase activity (P < 0.01), and at 7 h, it also decreased the ability of insulin to suppress EGP (P < 0.001). G-6-P content was comparable in all groups. In vivo glucose-6-phosphatase and glucokinase activities did not correspond to their in vitro activities as determined in liver tissue, suggesting that stable changes in enzyme activity were not responsible for the FFA effects. The data suggest that, in overnight-fasted rats, FFA increased basal EGP and induced hepatic insulin resistance at different sites. 1) FFA increased basal EGP through an increase in TGO and in vivo glucose-6-phosphatase activity, presumably due to a stimulatory allosteric effect of fatty acyl-CoA on glucose-6-phosphatase. 2) FFA induced hepatic insulin resistance (decreased the ability of insulin to suppress EGP) through an impairment of insulin's ability to increase GC and in vivo glucokinase activity, presumably due to an inhibitory allosteric effect of fatty acyl-CoA on glucokinase and/or an impairment in glucokinase translocation.  相似文献   

19.
The effects of morphine on lipid levels of plasma and liver were studied in rats. The first injection of morphine induced a decrease in free fatty acids (FFA) and an increase in the plasma triglyceride level. No changes in phospholipid, cholesterol or cholesterol ester concentrations were observed. In chronic morphinized rats the plasma FFA level was unchanged one hour following the injection of morphine and tolerance developed to the depressive effect of the drug. In contrast, the rise in plasma triglycerides persisted, but to a lesser extent. In these animals, the plasma levels of FFA and of triglycerides were lower than in normal rats, when blood was sampled 24 hours after the last injection of morphine. In abstinent rats, a reversal of action of morphine was noticed. Nalorphine induced an increase in plasma FFA levels in normal and abstinent rats but not in chronically morphine-treated animals. In the liver no significant changes occured in lipids in either acute or chronically morphinized rats. The effects of morphine on plasma lipid levels might be linked to the action of the drug on the secretory activity of the adrenals and also to the depressive effect of the drug on the lipolytic activity of adipose tissue which was demonstrated in vitro.  相似文献   

20.
Significant increases in circulating levels of free fatty acids (FFA) and growth hormone (GH), were observed in homing pigeons after a flight of 48 km, lasting 60-80 min. No significant change in plasma levels of thyroxine (T4) and triiodothyronine (T3) was observed. Nor was there any change in T3/T4 ratio. The increase in plasma FFA is attributed to the increased release into circulation of at least one adipokinetic hormone, GH. It may be concluded that in free sustained homing flight under normal weather conditions and within the specific distance and duration, metabolic fuel and hormonal homeostasis is maintained.  相似文献   

设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号