胆固醇对胆固醇结石形成和胆囊离体肌条的影响

目的 探讨胆固醇与胆囊动力的关系及其在胆固醇结石形成中的作用.方法 构造豚鼠胆固醇结石模型,检测各组豚鼠血清胆固醇(TC)及胆汁胆固醇(BC)含量;利用灌流法加药,张力换能器记录胆囊收缩素对各组离体胆囊肌条张力的变化,并初步探讨胆固醇对胆囊肌条的作用机制.结果 A组(正常豚鼠)无结石发生,B、C两组(致石饲料4周、8周)共有13例结石发生;B、C两组TC和BC升高(与A组相比P<0.05),加入CCK后收缩振幅均增加,呈浓度依赖性.且与TC、BC相关(P<0.05);同A组相比,B、C及D(胆固醇孵育后胆囊肌条)三组对CCK效应值变小,起作用时间慢(P<0.05);CCK对胆囊离体肌条的作用可以部分被胆固醇抑制(变化为69.2%,P<0.05),而胆固醇的影响可以部分被阿托品、尼莫地平抑制(变化分别为64.2%、62.1%,P<0.05),不被TTX影响(P>0.05).结论 TC及BC增高的同时胆囊肌条肌张力降低及对CCK的敏感性降低,成石率增高;胆固醇孵育后肌条肌张力降低及对CCK的敏感性降低;胆固醇可能与胆囊动力及胆固醇结石形成相关.     

绞股蓝预防豚鼠胆囊胆固醇结石形成

目的 探讨胆固醇结石的预防。方法 采用豚鼠为实验对象，随机分为三组，设置了空白组、对照组、预防组。结果 药物预防组较对照组成石率显著降低（P＜0．05），药物预防组胆汁中胆固醇含量较对照组显著降低（P＜0．05），胆汁酸含量较对照组显著升高（P＜0．05）。结论 绞股蓝能改善肝功能细胞，降低胆汁中胆固醇含量，提高胆汁酸含量，达到预防胆固醇结石形成的目的。     

胆囊在胆固醇结石形成中的作用研究进展（文献综述）

胆囊是胆固醇结石形成的场所,胆固醇结石形成并不完全依赖于胆汗的物理化学成分改变,胆囊功能改变在胆固醇结石形成中起重要的作用,本文从胆囊粘膜功能异常,胆囊收缩功能异常,胆囊结石与肠道功能改变几个方面作一综述。     

豚鼠胆囊胆固醇结石形成过程中小肠动力的变化

目的 观察豚鼠胆囊胆固醇结石形成过程中小肠动力的变化,探讨其在胆囊结石形成中的作用.方法 将40只豚鼠随机分为实验组与对照组,每组20只,实验组给予致石饲料(胆固醇含量2％),对照组给予正常颗粒饲料,8周造模结束后,利用多通道生理记录仪分别记录实验组与对照组豚鼠离体小肠肌条慢波和张力变化,分析其与胆囊胆固醇结石形成的关系,组间比较采用t检验.结果 豚鼠小肠离体肌条慢波频率实验组为5.70±1.05次／min,对照组为17.45±1.50次／min,振幅实验组为0.23±0.31 mv,对照组为0.78 ±0.17 my,实验组数据较对照组明显降低,P值分别为:4.56×10-25,4.00×10-13,均＜0.05;组间比较t值分别为:-27.083,-13.236;豚鼠小肠离体肌条肌肉收缩频率实验组为5.94±1.25次／min,对照组为15.85±1.76次/min,张力效应值实验组为0.78±0.02g,对照组为1.20±0.11g,实验组数据较对照组明显降低,P值分别为2.41×10-20,1.55×10-13,均＜0.05;组间比较t值分别为:- 19.448,- 17.307.结论 致石组豚鼠小肠动力较对照组明显下降,提示小肠动力异常可能在胆囊胆固醇结石形成过程中发挥作用.     

三磷酸肌醇对大鼠离体逼尿肌肌条自发收缩作用的影响

目的:观察三磷酸肌醇(IP3)对大鼠逼尿肌肌条自发收缩频率及收缩幅度的作用。方法:建立逼尿肌不稳定(DI)大鼠模型,制作大鼠离体逼尿肌肌条,比较同等张力下DI及逼尿肌稳定(detrusorstability,DS)组逼尿肌肌条自发收缩频率和收缩幅度的变化,观察不同浓度IP3及其抑制剂肝素对二组肌条自发收缩频率和收缩幅度的影响。结果:大鼠膀胱下尿路梗阻6周后DI发生率为57.4%。同等张力下,DI组肌条自发收缩频率显著高于DS组(P<0.01),收缩幅度显著低于DS组(P<0.01)。IP3能显著增加DI、DS大鼠逼尿肌肌条自发收缩频率及收缩幅度(P<0.01),肝素能显著抑制DI鼠逼尿肌肌条的自发收缩频率(P<0.05),但对其收缩幅度没有显著影响(P<0.05)。结论:IP3能显著提高大鼠逼尿肌肌条自发收缩频率和收缩幅度,DI逼尿肌自发兴奋性升高可能与IP/Ca2 信号通路的改变有密切联系。     

胆固醇结石形成机制的基因研究现状与展望

1986年。在美国召开首届国际胆石病预防会议,时隔20余年,在2008年消化学科的权威杂志《Gastroenterology》,发表了用Ezetimibe预防胆石病的实验和临床研究,可见在胆石病研究领域,时刻关注和“执着追求”胆石病的预防。胆石病是世界范围的常见病,其大多指胆囊结石,常见主要成分是胆固醇,属于胆固醇类结石,全国两次胆石病调查结果显示我国胆囊结石的比例正逐渐增加,     

胆汁中蛋白成分对胆固醇结石形成的影响

胆囊胆固醇结石的形成常与胆汁成分改变有关，但其确切机制及其始动因素尚未完全明了，该文就近年胆汁中蛋白质成分改变对胆石形成的影响及其可能机制方面研究成果作一综述。     

免疫与胆囊胆固醇结石的形成

胆囊胆固醇结石是一种多因素疾病，目前发现胆囊胆固醇结石的形成与免疫有关系，本文将介绍这方面研究的最新动向。     

Effects of cholecystokinin on gallbladder stasis and cholesterol gallstone formation

Recent studies suggest an etiologic role for gallbladder stasis in the genesis of cholesterol gallstones. The effect of periodic gallbladder emptying on stone prevention is not clear. Using the prairie dog model, we tested the hypothesis that daily cholecystokinin-octapeptide (CCK-OP) prevents gallbladder stasis and cholesterol gallstone formation. Prairie dogs were fed either a control or a 0.4% cholesterol-enriched chow for 6 weeks. Cholesterol-fed animals received a daily intramuscular injection of either saline, CCK-OP, 0.2 μg/kg or CCK-OP, 1.0 μg/kg. Gallbladder bile lithogenic index (LI), bile salt pool size (BSPS), and the degree of radioisotope equilibration between gallbladder and hepatic bile (Rsa-an index of stasis) were determined. The more physiologic dose of CCK-OP (0.2) significantly reduced BSPS and bile lithogenicity, prevented stasis and reduced the incidence of gallstones. Our data suggest that (1) periodic gallbladder emptying decreases bile lithogenicity, prevents stasis, and reduces the incidence of cholelithiasis, (2) stasis is essential to gallstone formation and (3) daily physiologic doses of CCK-OP may be useful for gallstone prophylaxis in high-risk patients.     

胆道口括约肌运动功能与豚鼠胆固醇结石形成关系的研究

目的研究胆道口(Oddi)括约肌运动功能在豚鼠胆囊胆固醇结石形成过程中的作用。 方法34只成年雄性Hartley豚鼠随机分为胆固醇结石组(24只)和对照组(10只),其中胆固醇结石组(按被处死的时间,分为4个亚组,各6只)给予致石饮食,3、6、9、12周后对两组行胆道口括约肌测压并检测肌电活动。 结果胆固醇结石组3、6、9、12周的发生率分别为0、16.7%、16.7%、83.3%。肌电活动的频率在3周组和6周组减小(均P < 0.05),肌电活动幅度在9周组和12周组明显降低[从(146.44 ± 81.09) μV分别降至(68.18 ± 49.58) μV和(40.60 ±45.03) μV, P <0.05]。胆道口括约肌收缩频率在6周组和9周组明显减小(P < 0.05)。胆道口括约肌基础压及胆总管压在12周组明显升高[从(25.19 ± 7.77) mmHg至(52.38 ± 12.84) mmHg,(22.35 ± 7.60) mmHg至(50.11 ± 12.59) mmHg,均P < 0.01]。 结论致胆固醇结石饮食能诱发胆道口括约肌功能紊乱,其张力增加、活动性下降。胆道口括约肌运动功能紊乱是胆色素结石形成的一个重要因素。     

Effect of peritonitis on gallbladder smooth muscle contractility in guinea pigs

BACKGROUND: The mechanisms involved in the impaired gallbladder contractile response in peritonitis are unknown. The aim of this study was to determine the effect of peritonitis on the contraction and relaxation responses to different agonists in gallbladder smooth muscle in guinea pig. MATERIALS AND METHODS: Peritonitis was induced by cecal ligation and puncture (CLP) in 10 guinea pigs. Another group of 10 guinea pigs underwent a sham operation and acted as controls. Twenty-four hours after the operation, the guinea pigs were killed, and gallbladder strips were placed in organ bath. The contraction responses to KCl, carbachol, and histamine, and relaxation responses to cyclooxygenase inhibitors (indomethacin, nimesulide, and DFU) on KCl-induced contractions were recorded. RESULTS: There was no significant difference between the contractile responsiveness to KCl, but maximum contractile responses (E(max)) to carbachol and histamine were significantly reduced. Indomethacin, nimesulide, and DFU concentration dependently inhibited on KCl-induced contractions of gallbladder smooth muscle. E(max) values of indomethacin, nimesulide, and DFU were significantly reduced in the peritonitis group compared with controls (P < 0.05). The inhibitor effects of nimesulide and DFU were considerably similar, but inhibitor effect of indomethacin was significantly less than that measured for nimesulide and DFU in both control and peritonitis groups (P < 0.05). CONCLUSIONS: The contraction responses to carbachol and histamine and relaxation responses to COX inhibitors on gallbladder smooth muscle are significantly decreased by peritonitis. Although the mechanism of the decrease in contraction and relaxation responses in CLP-induced peritonitis is completely unknown, we speculate that impaired smooth muscle responses may be related to an alteration in the regulation of receptor/postreceptor excitation-response coupling and/or through changes on Ca(2+) influx.     

Effect of dietary ethanol on gallbladder absorption and cholesterol gallstone formation in the prairie dog

Dietary ethanol has been reported to protect against cholesterol gallstone formation. Because enhanced gallbladder absorption of water is important in cholesterol cholelithiasis, we examined the hypothesis that ethanol acts by inhibiting the absorptive function of the gallbladder. Eighteen adult male prairie dogs were fed a lithogenic liquid diet containing 0.4% cholesterol. Half of the animals received 30% of total calories as ethanol, whereas their pair-fed controls received equicaloric amounts of maltose-dextrin. After 3 months, the gallbladders were inspected for gallstones and crystals, and gallbladder and hepatic bile were analyzed. Cholesterol stones and crystals were present in all nine controls. None of the alcohol-fed animals had stones, but four had cholesterol crystals. Gallbladder cholesterol, phospholipids, and total calcium were significantly decreased in alcohol-fed animals. In both gallbladder and hepatic bile, the cholesterol saturation index was significantly lower in alcohol-fed animals, as was the ratio of trihydroxy to dihydroxy bile salts. The ethanol-supplemented diet produced a significant decrease in the absorption of water by the gallbladder as indicated by changes in the gallbladder bile to hepatic bile ratios of the total bile salt concentration (7.29 +/- 1.25 versus 3.84 +/- 0.56; p less than 0.05) and the total calcium (3.37 +/- 0.24 versus 2.43 +/- 0.29; p less than 0.05). These findings indicate that the protective effect of ethanol may be related to its ability both to inhibit gallbladder absorption of water and to alter the composition of biliary lipids.     

Effect of bile diversion and sphincterotomy on gallbladder muscle contractility and gallstone formation

Feeding prairie dogs a diet rich in cholesterol induces gallstone formation that is preceded by a sustained decrease in gallbladder smooth muscle contractility. Sphincterotomy is known to prevent gallstone formation in cholesterol-fed prairie dogs. Experiments were designed to determine whether the effect of sphincterotomy is a consequence of hepatic bile diversion, and whether bile diversion prevents the altered contractility. Following sham operation, surgical biliary enteric bypass, or sphincterotomy, prairie dogs were fed a high-cholesterol or a regular diet. Gallbladder muscle contractility and the presence of crystals and stones were determined. In sham-operated animals, the cholesterol diet induced a decrease in gallbladder muscle contractility and caused the formation of cholesterol gallstones. In animals with bile diversion and sphincterotomy, the effects of cholesterol feeding were reduced or prevented. Thus, these procedures may prevent stone formation by preventing a reduction in gallbladder contractility. Contractility was depressed in animals with bile diversion fed a regular diet, compared with animals with a sham operation fed a regular diet. The mechanism for this depression may differ from that induced by the cholesterol diet. Diversion, and perhaps sphincterotomy, impairs gallbladder filling. Thus, gallbladder muscle is not stretched and does not contract against a load. This could result in a "disuse atrophy." If the results from our study apply to humans, sphincterotomy may reduce stone formation by preventing the effects of lithogenic bile on gallbladder muscle contractility and by enhancing the ability of the muscle to empty the lithogenic bile.