共查询到20条相似文献,搜索用时 46 毫秒
1.
Miller P Roy A St-Pierre S Dagenais M Lapointe R Poitras P 《American journal of physiology. Gastrointestinal and liver physiology》2000,278(1):G18-G23
Motilin is an intestinal peptide that stimulates contraction of gut smooth muscle. The motilin receptor has not been cloned yet, but motilin-receptor agonists appear to be potent prokinetic agents for the treatment of dysmotility disorders. The aim of this study was to determine neural or muscular localization of motilin receptors in human upper gastrointestinal tract and to investigate their pharmacological characteristics. The binding of (125)I-labeled motilin to tissue membranes prepared from human stomach and duodenum was studied; rabbit tissues were used for comparison. Solutions enriched in neural synaptosomes or in smooth muscle plasma membranes were obtained. Various motilin analogs were used to displace the motilin radioligand from the various tissue membranes. The highest concentration of human motilin receptors was found in the antrum, predominantly in the neural preparation. Human motilin receptors were sensitive to the NH(2)-terminal portion of the motilin molecule, but comparison with rabbit showed that both species had specific affinities for various motilin analogs [i.e., Mot-(1-9), Mot-(1-12), Mot-(1-12) (CH(2)NH)(10-11), and erythromycin]. Motilin receptors obtained from synaptosomes or muscular plasma membranes of human antrum expressed different affinity for two motilin-receptor agonists, Mot-(1-12) and Mot-(1-12) (CH(2)NH)(10-11), suggesting that they correspond to specific receptor subtypes. We conclude that human motilin receptors are located predominantly in nerves of the antral wall, are functionally (and probably structurally) different from those found in other species such as the rabbit, and express specific functional (and probably structural) characteristics dependent on their localization on antral nerves or muscles, suggesting the existence of specific receptor subtypes, potentially of significant physiological or pharmacological relevance. 相似文献
2.
Motilin receptors in rabbit stomach and small intestine 总被引:10,自引:0,他引:10
Motilin receptors in rabbit antral and duodenal smooth muscle tissue were characterized by direct binding technique using 125I-labeled porcine motilin as a tracer ligand. Binding at 30 degrees C was maximal at 90 min, was saturable and partially reversible. Displacement studies with natural porcine motilin, synthetic leucine-motilin or norleucine-motilin indicated a dissociation constant (Kd) of 1.1 +/- 0.3 nM and a maximal binding capacity (Bmax) of 42 +/- 10 fmol/mg protein. Binding was unaffected by glucagon, pancreatic polypeptide and somatostatin, but substance P interfered via an unknown mechanism. By density gradient centrifugation motilin receptors were shown to be present in plasma membranes. Binding could only be demonstrated in preparations from antrum and upper duodenum. These observations provide evidence for a localized target region for motilin in the gastrointestinal tract, and for a direct interaction of motilin with gastrointestinal smooth muscle tissue. 相似文献
3.
Motilin is involved in the regulation of the fasting motility pattern in man and in dog, but may have a different role in other species. Immunoreactive motilin has been demonstrated in several species, but the sequence is mostly unknown. The aim of this study was to isolate and sequence the cDNA encoding the motilin precursor from several mammalian species and from chicken. Total RNA was isolated from the duodenal mucosa of the chicken, dog, cow and horse. In each case single stranded cDNA was synthesized. Motilin cDNA fragments were amplified by PCR, ligated into a plasmid and cloned. Clones which were positive after screening with an appropriate (32)P-labeled probe were sequenced. The 5'- and 3'-ends were determined by the rapid amplification of cDNA ends (RACE) method. Analysis of the cDNAs revealed an open reading frame coding for 115 (chicken and cow), or 117 (dog and horse) amino acids. It consists of a 25 amino acid signal peptide, motilin itself, and a 68 (chicken and cow) or 70 (dog and horse) amino acid motilin associated peptide (MAP). As in all motilin precursors already sequenced (man, monkey, pig and rabbit), an endoproteinase cleavage site is present at Lys(23)-Lys(24). Comparison of all known sequences shows considerable identity in amino acid and nucleotide sequence of the signal peptide and motilin. However, the MAPs differ not only in length but also, more strongly, in amino acid and nucleotide sequence. Our study demonstrates that the N- and C-terminal regions of the motilin precursor have evolved at different rates, which is evidence for 'mosaic evolution'. 相似文献
4.
Due to motilin's relation to the migrating motor complex (MMC), the physiology of motilin has been mostly studied in man and dog. The cat does not have an MMC pattern, and little is known about cat motilin. Therefore we identified the cat motilin precursor (GenBank accession no. AF127917) and developed a quantitative polymerase chain reaction (PCR) to explore its distribution in the gastrointestinal tract and in the central nervous system (CNS). The precursor is closely related to the dog precursor and consists of an open reading frame of 348bp encoding the signal peptide (25 amino acids), the motilin sequence (22 amino acids) and the motilin associated peptide (69 amino acids). One amino acid of the signal peptide was subject to gene polymorphism. Quantification of motilin messenger RNA (mRNA) was for the first time achieved. It is most abundant in the gastrointestinal tract, with the highest concentration in the duodenum, the lowest in the colon and is not detectable in the corpus. However an important expression was also observed in several regions of the CNS, except the striatum and cerebral cortex. The highest level was in the hypothalamus (although 23-fold lower than in the duodenum), the lowest level in the pons. Moderate levels were found in the thyroid. These data suggest that the physiological role of motilin may extend beyond its effect on gastrointestinal motility. 相似文献
5.
Bin Feng Jin-cheng Liu Jun Zhang Ken-ichi Ozaki Yan-yan Guo Ding-hua Yi Xiao-qiang Li Ming-gao Zhao 《Molecular neurobiology》2013,47(3):892-902
Motilin is a 22-amino-acid gastrointestinal polypeptide that was first isolated from the porcine intestine. We identified that motilin receptor is highly expressed in GABAergic interneurons in the basolateral nucleus (BLA) of the amygdala, the structure of which is closely involved in assigning stress disorder and anxiety. However, little is known about the role of motilin in BLA neuronal circuits and the molecular mechanisms of stress-related anxiety. Whole-cell recordings from amygdala slices showed that motilin depolarized the interneurons and facilitated GABAergic transmission in the BLA, which is mimicked by the motilin receptor agonist, erythromycin. BLA local injection of erythromycin or motilin can reduce the anxiety-like behavior in mice after acute stress. Therefore, motilin is essential in regulating interneuron excitability and GABAergic transmission in BLA. Moreover, the anxiolytic actions of motilin can partly be explained by modulating the BLA neuronal circuits. The present data demonstrate the importance of motilin in anxiety and the development of motilin receptor non-peptide agonist as a clear target for the potential treatment of anxiety disorders. 相似文献
6.
Motilin and motilin receptors have been found in most regions of the brain, including the amygdala, one of the most important parts of the limbic system. Our previous study found that administration of motilin in the hippocampus stimulates gastric motility. We now explore the effect of motilin in the amygdala on gastric motility. In conscious rats, gastric motility was recorded after microinjection of motilin, motilin receptor antagonist (GM-109) or a mixture of the two into the basomedial amygdala nucleus (BMA). In anesthetized rats the changes of spontaneous discharges of gastric distention sensitive neurons (GDSN) in the BMA were recorded after intracerebroventricular (i.c.v.) microinjection of motilin or GM-109. In conscious rats the amplitude of gastric contractions increased dose-dependently after microinjection of motilin in the BMA, and decreased after microinjection of GM-109. The excitatory or inhibitory effects induced by motilin or GM-109 alone, were weakened by microinjection of a mixture solution of both. The spontaneous discharge frequency of gastric distention excitatory neuron (GDEN) was mainly inhibited by i.c.v. microinjection of motilin but excited by GM-109. In contrast, the spontaneous discharge frequency of gastric distention inhibitory neuron (GDIN) was mainly excited by motilin, but inhibited by GM-109. Our findings suggest that motilin may regulate gastric motility by modulating neural pathways in the BMA. 相似文献
7.
D K Banfield R T MacGillivray J C Brown C H McIntosh 《Biochimica et biophysica acta》1992,1131(3):341-344
The cDNA sequence of rabbit motilin precursor has been determined. The predicted amino acid sequence indicates that the precursor consists of 133 amino acids and includes a 25 amino acid signal peptide followed by the 22 amino acid motilin sequence and an 86 amino acid motilin associated peptide (MAP). As in the human and porcine precursors, two lysine residues follow motilin in the rabbit sequence. Rabbit motilin shares 64% amino acid sequence identity with human and porcine motilin, and all amino acid substitutions represent conservative changes. Amino acid sequence alignments of the rabbit, human and porcine MAP sequences suggest three functional/structural motifs corresponding to a putative endoproteinase recognition site, a putative PEST site and a potential posttranslational processing recognition element. 相似文献
8.
Although peripheral actions have been shown for the brain-gut peptide, motilin, its localization in the CNS of mammals suggests some physiological role at this site. In the present experiments intracerebroventricular or intrathecal, but not peripheral, administrations of motilin produced a dose-related and naloxone reversible inhibition of the micturition reflex. Cross-tolerance was demonstrated between motilin and morphine in this respect. These data suggest a physiological role for motilin within CNS to alter urinary bladder motility, possibly through an enkephalinergic or naloxone-sensitive link. 相似文献
9.
目的:研究人甲状腺髓样癌TT细胞系中胃动素基因表达调控.方法:通过人甲状腺髓样癌TT细胞体外培养,观察经cAMP,生长激素或甲状腺雌激素诱导后,胃动素表达的改变以及胃动素对TT细胞生长、侵袭和转移的影响.结果:甲状腺髓样癌TT细胞表达胃动素mRNA,胃动素可抑制TT细胞的生长.当胃动素基因沉默后,TT细胞转移和侵袭能力增加.当TT细胞分别经cAMP、胃动素、生长激素或甲状腺刺激素孵育48小时后,胃动素基因转录增加,降钙素基因相关肽与胃动素mRNA比值持续下降.环磷酸腺苷可降低TT细胞增殖和c-myc基因的表达.结论:人甲状腺髓样癌细胞生长活性可能与甲状腺C细胞(低的降钙素基因相关肽与胃动素比率)分化的表型有关. 相似文献
10.
We demonstrate binding of [125I][Nle13-po]motilin to homogenates of cat gastric and small intestinal, but not to colonic smooth muscle tissue. The density was (Bmax in fmol/mg protein): 0 (fundus); 12 ± 2 (corpus); 22 ± 3 (antrum); 55 ± 12 (duodenum); 44 ± 10 (jejunum); 17 ± 1 (ileum); 0 (colon). A significant (p < 0.05) difference was found between the dissociation constant for motilin in the stomach (pKd = 8.84 ± 0.06) and in the small intestine (pKd = 8.58 ± 0.08). The motilides erythromycin-A (EM-A), EM-523, and EM-A N-oxide displaced labeled [Nle13-po]motilin bound to cat duodenal receptor with potencies (pKd) of 5.47 ± 0.23, 7.60 ± 0.24, and < 4.3, respectively. Studies with [Leu13-po]motilin fragments showed that the N-terminus of motilin interacts with the receptor. In the tissue bath, duodenal strips mounted in the longitudinal direction responded to motilin, EM-523, and EM-A (pEC50: 8.29 ± 0.08; 7.12 ± 0.12; 5.99 ± 0.15). The compounds had a comparable intrinsic activity (83 ± 3%; 80 ± 5%; 82 ± 5% of the response to ACh), which was unaffected by atropine, TTX, hexamethonium, and zacopride but reduced by verapamil and calcium-free medium. Cat stomach and small intestine possess smooth muscle motilin receptors, which have comparable properties as those found in man and in rabbit. 相似文献
11.
M Lemoyne R Wassef D Tassé L Trudel P Poitras 《Canadian journal of physiology and pharmacology》1984,62(9):1092-1096
The aim of this work was to determine the influence of the vagus on the circulating levels of immunoreactive (IR) motilin. Five mongrel dogs were equipped with chronically implanted electrodes in the small intestine to record the myoelectrical activity. The release of IR motilin during fasting, after a meal, and during an infusion of insulin was studied before and after truncal vagotomy at the diaphragmatic level. When tested at least two weeks after the operation, the motility pattern of the small intestine and the secretion of IR motilin remained unaltered by vagal section. Cyclic increases in IR motilin associated with phase III's of the interdigestive myoelectric complexes were still observed after vagotomy (maximum levels of IR motilin: 250 +/- 37 versus 239 +/- 19 fmol X mL-1, not significant), and they were still abolished by feeding or by insulin. However, an inhibitory influence can probably be mediated by the vagus since, in normal animals, vagal stimulation by a "modified sham feeding" (tease feeding or presentation of food) at the beginning of a period of phase III activity promptly interrupted this part of the complex and decreased significantly the release of IR motilin by about 20%. The release of motilin is not chronically altered by distal vagotomy in dogs. 相似文献
12.
Erythromycin may stimulate gastrointestinal motor activity via its effect upon motilin receptors. We have studied the ability of the derivative EM-523 [de(N-methyl)-N-ethyl-8,9-anhydroerythromycin A 6,9-hemiacetal] to induce contractions in duodenal smooth muscle strips and to displace labeled motilin bound to antral smooth muscle, in man and in rabbit. In both species EM-523 approached the potency of motilin for inducing contractions. Thus pED50 values were 7.84 +/- 0.11 and 8.69 +/- 0.12 for motilin in, respectively, man and rabbit, against 6.08 +/- 0.13 and 8.19 +/- 0.10 for EM-523. In rabbit the efficacy of both compounds decreased in parallel aborally, the responses to EM-523 could not be blocked by atropine (10(-7) M) or TTX (10(-7) M), and both compounds were unable to further enhance the maximum effect to the other compound. In binding studies the order of potency was the same as in the contraction studies. The pIC50 values were: motilin (8.84 +/- 0.31, 9.17 +/- 0.20) greater than EM-523 (7.89 +/- 0.1, 8.40 +/- 0.10). A Schild plot revealed that EM-523 was a competitive inhibitor of motilin receptor binding in man and in rabbit. We conclude that EM-523 is a potent motilin agonist. 相似文献
13.
Miegueu P Cianflone K Richard D St-Pierre DH 《American journal of physiology. Endocrinology and metabolism》2011,301(5):E758-E766
Motilin is a circulating gastrointestinal peptide secreted primarily by duodenal mucosal M cells and recognized for its prokinetic effects on gastrointestinal tissues. Little information is available regarding effects on insulin/glucose homeostasis or adipocyte function. Our aim was to evaluate the effects of motilin on adipocyte proliferation, differentiation, lipolysis, and macronutrient uptake in adipocytes. 3T3-L1 cells and primary rat adipocytes were treated acutely and chronically with varying motilin concentrations, and effects were compared with vehicle alone (control), set as 100% for all assays. In preadipocytes, motilin stimulated proliferation ([(3)H]thymidine incorporation) and mitochondrial activity (141 ± 10%, P < 0.001 and 158 ± 10%, respectively, P < 0.001), in a concentration-dependent manner. Chronic supplementation with motilin during differentiation further increased lipogenesis (Oil red O staining 191 ± 27%, P < 0.05) and was associated with an upregulation of PPARγ (148 ± 8%, P < 0.01), C/EBPα (142 ± 17%, P < 0.05), and Cav3 (166 ± 20%, P < 0.05) expression. In mature 3T3-L1 adipocytes motilin increased fatty acid uptake/incorporation (≤ 202 ± 12%; P < 0.01) and glucose uptake (146 ± 9% P < 0.05) and decreased net fatty acid release (maximal -31%, P < 0.05) without influencing total lipolysis (glycerol release). Similar effects were obtained in primary rat adipocytes. Motilin acutely increased expression of PPARγ, CEBPβ, DGAT1, and CD36 while decreasing adiponectin mRNA and secretion. In human adipose tissue, motilin receptor GPR38 correlated with HOMA-IR and GHSR1 (r = 0.876, P < 0.0001). Motilin binding and fatty acid incorporation into adipocytes were inhibited by antagonists MB10 and [D-lys3]-GRP6 and PI 3-kinase inhibitor wortmannin. Taken together, these results suggest that motilin may directly influence adipocyte functions by stimulating energy storage. 相似文献
14.
M Boivin M Riberdy M C Raymond L Trudel P Poitras 《Canadian journal of physiology and pharmacology》1992,70(11):1491-1495
This study was designed to establish whether the rise in plasma motilin observed after a meal in humans can influence the postprandial motor activity of the antrum. Antroduodenal postprandial motility profiles and indices obtained from 5 controls and 5 subjects infused with exogenous synthetic motilin (0.1 microgram.kg-1) or with the motilin receptor agonist erythromycin lactobionate (200 mg) were compared. Motilin infusion increased plasma motilin concentrations about 5 times above the physiological range but failed to modify the normal postprandial contractile response. On the other hand, in 4 of the 5 subjects, erythromycin induced an intense motor response that mimicked phase III of the migrating motor complex. Our study demonstrates that, during the postprandial period, motilin antral receptors can be stimulated only with doses of motilin exceeding the physiological plasma concentrations, and that the motor effect obtained did not mimic the usual postprandial motility pattern. Our results, therefore, do not support the proposal that the postprandial motility of the antrum is regulated by the plasma levels of motilin. 相似文献
15.
Camacho-Arroyo I Mendoza-Rodríguez CA Mendoza-Garcés L Vanoye-Carlo A Cerbón M 《The Journal of steroid biochemistry and molecular biology》2007,104(3-5):100-104
Progesterone regulates diverse functions in the rabbit brain through the interaction with its nuclear receptor (PR). Although PR protein has been detected in some regions of the rabbit forebrain, PR mRNA expression and distribution in the rabbit brain are unknown. Hence, we investigated these issues by in situ hybridization. New Zealand adult female rabbits were ovariectomized and treated with vehicle or estradiol (5 μg/(kg day)) for 3 days. The results show an extended distribution of PR mRNA expression in the rabbit brain. The highest expression was detected in preoptic area and hypothalamic anterior nuclei such as paraventricular, periventricular and arcuate nuclei. A high expression was also detected in thalamic and telencephalic areas, including hippocampus and cerebral cortex. Estradiol treatment induced an increase in PR mRNA expression in many brain areas, particularly in the hippocampus and the hypothalamic and preoptic area regions. The wide distribution of PR mRNA in the rabbit brain suggests that progesterone through PR activation is involved in several functions apart from reproductive behavior in rabbits, and that PR expression is up-regulated by estradiol in the rabbit brain. 相似文献
16.
Characterization of complementary deoxyribonucleic acid for precursor of porcine motilin 总被引:2,自引:0,他引:2
C T Bond G Nilaver B Godfrey E A Zimmerman J P Adelman 《Molecular endocrinology (Baltimore, Md.)》1988,2(2):175-180
Cloned cDNAs encoding the precursor protein for motilin and a novel peptide, motilin-associated peptide, were isolated from a library derived from porcine intestinal mucosa mRNA. Nucleotide sequence analysis predicts a precursor protein of 119 amino acids including a signal peptide in direct linkage with the 22 amino acid sequence for motilin, and a 70 amino acid peptide of unknown function. The putative bioactive moieties are separated by Lys-Lys, dibasic residues that serve as substrates for cleavage by proteolytic maturation enzymes in many polyprotein precursors. While there is an abundant literature detailing a spectrum of tissues and cell types which express motilin like immunoreactivity, analysis of mRNA derived from many of these tissues suggests that the mRNA for the mucosal motilin precursor is only transcribed in this tissue. The nature of the immunoreactive material in the central nervous system and other peripheral tissues remains to be determined. 相似文献
17.
to investigate the regulatory mechanism of motilin release, plasma motilin was measured by radioimmunoassay in healthy dogs during the fasting state and after intravenous administration of various nutrients and somatostatin. The fasting plasma motilin levels of these dogs were found to fluctuate intermittently. Intravenous glucose loading lowered plasma motilin, but immediately after the end of the glucose infusion as abrupt rise of plasma motilin was observed. Mixed amino acids administered intravenously abruptly inhibited motilin secretion, and plasma motilin levels remained low even 45 min after the end of the infusion. On the other hand, no remarkable change in plasma motilin was noted after the fat infusion. Following somatostatin infusion, plasma motilin was significantly decreased, remaining low even 30 min after the end of the infusion. These observations led us to conclude than motilin secretion is regulated by somatostatin and by nutrients coming through intravenous routes. 相似文献
18.
Comparison of motilin binding to crude homogenates of human and canine gastrointestinal smooth muscle tissue 总被引:10,自引:0,他引:10
Pharmacological studies indicate that in man and in rabbit, but not in dog, motilin has a direct influence upon gastrointestinal smooth muscle. In accordance with this hypothesis we have presented direct biochemical evidence for the presence of motilin receptors on rabbit smooth muscle tissue. We have now extended our studies to human and canine tissue. Tissue homogenates were studied in binding experiments with iodinated porcine [Leu13]motilin and iodinated canine motilin. It was ascertained that the iodination procedure had little effect on the biological activity of the porcine analogue. In the human antrum specific binding of the iodinated porcine analogue was only found in the smooth muscle layer. It was absent in mucosal or serosal preparations. At 30 degrees C and pH 8.0, binding was maximal after 60 min of incubation, and was reversed by the addition of unlabeled porcine motilin. Binding was enhanced in the presence of calcium and magnesium ions. At a concentration of 10 mM MgCl2, binding was 220% of the binding observed in its absence. Displacement studies with synthetic porcine [Leu13]motilin or synthetic natural porcine motilin indicated a dissociation constant (Kd) of 3.6 +/- 1.6 nM and a maximal binding capacity (Bmax) of 77 +/- 9 fmol per mg protein. Canine motilin displaced iodinated porcine motilin with an apparent Kd of 2.2 +/- 0.9 nM. Compared to antral binding, receptor density decreased aborally and orally, and was absent in jejunum and ileum. In dog specific binding could not be demonstrated in antral and duodenal tissue, neither with labeled porcine nor with labeled canine motilin. However, labeled canine motilin was equipotent to labeled porcine motilin in binding studies with human tissue: the dissociation constant was 0.9 +/- 0.6 nM. The present studies therefore demonstrate the existence of a specific motilin receptor in the antroduodenal region of the human gut. Apparently, such receptors are not present in the canine gut. Our data support the hypothesis that in the human gastrointestinal tract, the gastroduodenal area is motilin's target region. 相似文献
19.
目的:研究尾悬吊模拟失重环境对大鼠血清胃泌素(GAS)、胃动素(MTL)和胃窦Cajal间质细胞(ICC)的影响。方法:健康雄性Wistar大鼠64只随机分为8组(rt=8),按模拟失重时相分别设为6h、12h、1d、2d、3d、5d、7d和0h(地面对照组)组,采用尾悬吊法建立模拟失重动物模型。应用放免法测定血清GAS、MTL浓度,免疫组化和RT—PCR技术检测各组大鼠胃窦组织中c—kit蛋白和mRNA表达情况。结果:尾悬吊6、12h阶段,血清GAS浓度明显升高,与对照组比较差异有统计学意义(P〈0.05);随尾悬吊时相延长,血清GAS含量呈逐渐下降趋势,与正常对照组水平相近。尾悬吊各组大鼠血清MTL浓度均升高,12h以后各组MTL浓度值与对照组比较,差异有统计学意义(P〈0.05)。免疫组化结果显示,c—kit蛋白阳性表达为棕褐色,主要分布在ICC胞体和突起,正常对照组大鼠胃窦肌层ICC(ICC—MY)呈连续性浓染,肌层内ICC(ICC—IM)亦明晰可见;6h-5d的尾悬吊过程中,大鼠胃窦ICC—MY连续性出现中断现象且逐渐明显,染色逐渐减弱,ICC—IM染色减弱的同时c—kit阳性ICC也明显减少;7d组胃窦组织中c—kit蛋白表达有所恢复。模拟失重各组及对照组大鼠胃窦组织中均有c—kitmRNA表达,尾悬吊6、12h组的c—kitmRNA表达明显下降,与对照组比较,差异有统计学意义(P〈0.05),1~3d组逐渐恢复,5d组又出现明显下降(P〈0.05),7d组c—kitmRNA表达值明显复升。结论:尾悬吊模拟失重对大鼠血清GAS、MTL和胃窦Cajal间质细胞c—kit蛋白及mRNA表达造成明显影响,可能导致胃动力障碍。 相似文献
20.
Motilin has never been isolated from rodents, the most frequently used laboratory animals, despite several attempts. We have isolated and sequenced the motilin precursor from duodenal mucosa of guinea pig (GenBank accession number AF323752) and studied its expression in several tissues. The percent homology with human motilin is the lowest yet observed due to several unique substitutions in the C-terminal end. As expected, the precursor was present in the gut mucosa with the exception of the gastric corpus. It was also present in medulla oblongata, nucleus of the solitary tract, hypophysis, spinal cord, hypothalamus, and cerebellum but not in the cerebral cortex. For the first time we demonstrated motilin expression in the thyroid. 相似文献