胆汁代谢相关调节蛋白与胆囊胆固醇结石

胆石病是常见的消化系统疾病,在我国随着人们生活方式和饮食结构改变等诸多因素的影响下,胆石病呈较快的上升趋势,部分地区患病率已达10%。同时,我国胆结石的类型也发生了很大的改变,胆囊结石约占胆石病的80%[1],以胆固醇为主要成分的胆囊结石已成为我国胆石病的主要发病类型。因此,研究胆囊胆固醇结石的发病机制具有重要意义。     

应用绞股蓝预防豚鼠胆囊胆固醇结石形成的实验研究

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 绞股蓝能改善肝细胞功能,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。     

胆、肠菌群差异性与胆囊胆固醇结石形成关系

目的 基于胆囊胆固醇结石患者胆道菌群、肠道菌群差异性,探讨胆、肠菌群交互与胆囊胆固醇结石形成关系.方法 选择2020年1月至2020年6月由沧州市人民医院诊疗的胆囊胆固醇结石患者42例为研究对象,记入胆固醇结石组;胆囊炎、胆囊息肉诊治等非胆固醇结石患者40例为非胆固醇结石组.采用Illumina测序技术测序并进行细菌O...     

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。     

胆囊胆固醇结石形成因素分子生物学研究进展

近年来胆囊结石的发病率呈逐渐上升的趋势,其中以胆囊胆固醇结石为主。目前胆囊胆固醇结石的成因仍不完全明确,本文就近年该病的分子物学的相关研究进展作一综述。     

神经鞘脂通路与胆固醇代谢的调控在胆囊胆固醇结石形成中的研究进展

胆囊结石(cholecystolithiasis)是一种常见、多发胆系疾病,按胆石的主要成分可分为胆固醇结石和胆色素结石两大类,我国成年人胆囊结石的发病率大概为10％,中年妇女甚至高达15％,其中70％以上的胆囊结石属胆固醇类结石[1].发达国家成年人胆结石发病率可达20％,而其中75％～80％以上为胆固醇结石[2,3...     

肠道菌群和胆汁酸的相互作用与多囊卵巢综合征

多囊卵巢综合征(PCOS)作为最常见的妇科内分泌紊乱疾病,影响着5%～10%的育龄期女性。PCOS具有临床复杂性和异质性,而其确切病因目前尚无定论。肠道微生物失调是PCOS代谢和生殖障碍的病因之一,PCOS与肠道菌群之间的联系逐渐成为生殖领域研究的热点。同时,肠道菌群与胆汁酸之间的紧密联系也逐渐被发现。肠道菌群可以调节胆汁酸的代谢及转化,而胆汁酸具有抗菌作用,可以影响肠道菌群的组成、结构和功能。胆汁酸和肠道菌群之间的相互作用参与了PCOS的发生发展。本文就胆汁酸和肠道菌群的相互作用与PCOS的关系进行综述,以期为PCOS的诊断和治疗及未来的研究方向提供一定参考。     

女性激素在胆囊胆固醇结石形成中的作用的研究现状

目的综述女性激素致胆囊胆固醇结石形成的机制,为预防雌、孕激素致石形成寻找途径。方法复习有关雌、孕激素致石形成的文献,总结其致石机制。结果雌激素主要通过核效应机制影响胆固醇代谢导致胆固醇结石形成,也可通过非核效应促使胆固醇成核及影响胆汁排空参与结石形成。孕激素通过核效应机制影响介导胆囊平滑肌收缩舒张的G蛋白α亚基损伤胆囊运动,通过非核效应途径影响离子通道及信号传导削弱胆囊运动,但孕酮的非核效应在结石形成中可能不起重要作用。结论女性激素致石机制复杂,明确其相关致石机制可为预防雌、孕激素致石形成开辟新途径。     

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汁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。     

肠道菌群对代谢术后骨代谢的影响

肠道菌群的改变对宿主起着多方面的影响。代谢手术对肠道结构及生理功能的改变影响了寄居于肠道内的菌群。而这些菌群的变化参与了术后体重下降﹑糖代谢及脂代谢的改变。同时已有很多研究证实肠道菌群的变化可以通过影响宿主的代谢系统﹑神经系统﹑免疫调节系统对骨代谢造成不容忽视的影响。益生菌作为一种对宿主有益的活性微生物,其骨保护作用也越来越得到重视。本文从减重术后肠道菌群的改变﹑肠道菌群对骨代谢的影响及益生菌与骨代谢等方面进行综述,总结近年来的研究进展及热点,搭建肠道菌群与代谢术后骨代谢相关多学科之间的桥梁,为代谢术后的菌群治疗、靶点研究奠定基础。     

胆囊结石中胆固醇代谢变化的实验研究

目的　探讨胆囊结石的胆固醇代谢变化。方法　采用高胆固醇膳食诱发兔胆囊结石模型 ,对进食高胆固醇膳食后 1,2 ,3,4周实验组和对照组血清脂蛋白胆固醇、肝脏总胆固醇 (HTC)、胆汁中胆固醇 (BC)和甘氨胆酸 (GCA) ,肝细胞低密度脂蛋白受体活性变化进行了动态研究。结果　高胆固醇膳食后 ,1周开始出现胆囊结石 ,2 ,3和 4周分别有 40 % ,6 0 % ,70 %出现胆囊结石。血清总胆固醇 (TC) ,甘油三酯 (TG ) ,磷脂 (PL) ,低密度脂蛋白胆固醇(LDL C)和极低密度脂蛋白胆固醇 (VLDL C) ,HTC ,BC均逐渐明显升高 (与对照组比较P均<0 .0 5 ) ;高密度脂蛋白胆固醇及其亚组分 (HDL C ,HDL2 C ,HDL3 C)有降低趋势 ,但无显著性差异 (P >0 .0 5 ) ;GCA逐渐降低 ,以 3周和 4周时明显 (P <0 .0 5 ) ;12 5I LDL与肝细胞低密度脂蛋白受体 (LDLr)最大结合力 (Bmax)在 1周组略升高 (P <0 .0 5 ) ,2周组逐渐下降 ,3周和 4周组时明显下降 (P <0 .0 5 ) ,解离常数Kd值逐渐升高 ,以 3周和 4周组明显 (P <0 .0 5 )。结论　随着高胆固醇膳食进食时间延长 ,血清及肝脏中胆固醇均增加 ,胆汁中胆固醇增加 ,肝细胞低密度脂蛋白受体活性下降 ,可能致胆汁中甘氨胆酸合成减少 ,成石性胆汁形成。提示胆固醇代谢中不同环节的变化均可在胆囊结石中     

Altered bile composition during cholesterol gallstone formation: cause or effect?

Gallbladder stasis, increased gallbladder absorption, and elevated biliary levels of calcium, hydrogen ion, and bilirubin have been implicated as factors potentially critical to cholesterol crystal precipitation. Previous studies, however, have analyzed bile only when crystals or gallstones have already formed. Therefore, we tested the hypothesis that changes in bile composition are a late effect, occurring only after crystal formation. Adult male prairie dogs were fed a standard nonlithogenic control diet (n = 7) or a lithogenic 1.2% cholesterol diet for 5, 9, or 14 days to cause cholesterol saturation (n = 7), cholesterol monohydrate crystals (n = 7), or gallstones (n = 7). Gallbladder bile was examined microscopically for crystals, and analyzed for ionized calcium, bilirubin, pH, total protein, and biliary lipids. The ratio of gallbladder to hepatic bile radiolabeled cholic acid specific activity (Rsa) was calculated as an index of gallbladder stasis. Cholesterol saturation index was calculated. The results demonstrate that increased gallbladder bile cholesterol saturation and total protein concentration precede cholesterol monohydrate crystal precipitation. However, changes in gallbladder ionized calcium, unconjugated bilirubin, pH, stasis, and absorption were noted only after crystals and gallstones had already formed. These data indicate that alterations in gallbladder bile calcium, bilirubin, pH, stasis, and absorption are not early changes, but occur simultaneously with or after crystal formation. Increased biliary protein, however, which was elevated prior to nucleation, may be an important mediator of cholesterol precipitation in cholesterol-saturated bile.     

Caffeine prevents cholesterol gallstone formation

Methylxanthines are known to inhibit in vitro gallbladder absorption. Increased gallbladder absorption has been observed during formation of cholesterol gallstones. Therefore we tested the hypothesis that caffeine would inhibit in vivo gallbladder absorption and thus prevent formation of cholesterol gallstones. Sixteen adult male prairie dogs received a control nonlithogenic diet, and 16 were fed a diet containing 1.2% cholesterol. Half of the animals in each group received caffeine in their drinking water. Gallbladder and hepatic bile were examined microscopically and analyzed for biliary lipids and electrolytes. The gallbladder/hepatic bile ratios of bile acids and sodium were calculated as indices of gallbladder absorption. All eight animals receiving the 1.2% cholesterol diet formed cholesterol gallstones, whereas none of the eight animals fed the cholesterol diet plus caffeine formed gallstones. The cholesterol saturation index was similar, however, in both groups. In animals fed a control diet, the administration of caffeine significantly increased hepatic bile flow and decreased the gallbladder/hepatic bile ratio for both bile acids (5.4 +/- 0.9 vs 3.6 +/- 0.3; p less than 0.05) and sodium (1.26 +/- 0.03 vs 1.12 +/- 0.03; p less than 0.01). In animals fed the high-cholesterol diet, caffeine significantly decreased the ratios for both bile acids (9.0 +/- 1.6 vs 5.3 +/- 0.6; p less than 0.05) and sodium (1.37 +/- 0.06 vs 1.21 +/- 0.01; p less than 0.05), lowered gallbladder bile protein levels, normalized gallbladder stasis, and lowered serum cholesterol levels. In summary, caffeine prevented formation of cholesterol gallstones in this experimental model. The effect of caffeine may be the result of alterations in multiple biliary parameters including the inhibition of gallbladder absorption.     

Dynamics of cholesterol gallstone dissolution in canine bile

The effects of comparable grades of gastric ischemia induced either by intraarterial infusion of vasopressin or by tourniquet occlusion of the arterial supply were assessed in 12 anesthetized dogs. An ultramicro-electrode technique was used to determine intracellular oxygen tension and transmembrane potential difference in mucosal epithelial cells; total gastric oxygen consumption was calculated as the product of total gastric blood flow and arteriovenous oxygen content difference. At equivalent grades of gastric ischemia, the tourniquet method reduced oxygen tension and potential difference significantly more than did the vasopressin method. Conversely, total gastric oxygen consumption was significantly inhibited by vasopressin ischemia, but not by tourniquet ischemia, at 50 and 25% of baseline gastric blood flow. Our results suggest that, during tourniquet ischemia, blood flow in the stomach is redistributed away from the mucosal epithelium. Vasopressin, on the other hand, maintains mucosal oxygenation and metabolism relatively well, possibly at the expense of total gastric oxygen consumption. We conclude that the two methods of producing gastric ischemia should not be used interchangeably to study gastric mucosal ulceration during severe stress states.     

Bilirubin monoglucuronide promotes cholesterol gallstone formation

Recent evidence suggests that cholesterol (Ch) solubility in bile is determined by a complex interaction of mixed micelles and lecithin-cholesterol vesicles. Bilirubin monoglucuronide (BMG), which binds to bile salts and incorporates into mixed micelles, may displace cholesterol from micelles into vesicles, thus favoring cholesterol monohydrate crystal precipitation. Therefore, we designed an experiment to test the hypothesis that BMG may enhance cholesterol gallstone formation without inducing cholesterol supersaturation. For 8 weeks, 28 adult male prairie dogs were fed either a control, nonlithogenic diet (0.03% Ch), a high carbohydrate diet (CHO) which has no cholesterol but increases hepatic bilirubin secretion, or the same CHO diet plus 0.03% Ch. Cholecystectomy was then performed, and bile was examined microscopically for stones or crystals and analyzed for BMG and biliary lipids. Cholesterol saturation index was calculated. Cholesterol gallstones were found in none of the control animals and in 13% of the CHO-fed animals. However, the addition of trace cholesterol to the CHO diet resulted in an 88% incidence of cholesterol gallstones (P less than 0.001 vs control, P less than 0.01 vs CHO, respectively). Gallbladder bile was unsaturated with cholesterol in all groups. (control = 0.65 +/- 0.05, CHO = 0.46 +/- 0.05, CHO + 0.03% Ch = 0.70 +/- 0.03). CHO feeding alone or with trace cholesterol significantly elevated gallbladder bilirubin monoglucuronide, phospholipid, and cholesterol concentrations when compared to controls. These data suggest that in the prairie dog a high carbohydrate diet with only trace amounts of cholesterol increases bilirubin monoglucuronide in gallbladder bile and causes cholesterol gallstone formation without inducing cholesterol supersaturation.(ABSTRACT TRUNCATED AT 250 WORDS)     

载脂蛋白E与胆囊胆固醇结石关系的研究

目的 探讨载脂蛋白Ｅ（ａｐｏｌｉｐｏｐｒｏｔｅｉｎ Ｅ）基因多态性与胆囊胆固醇结石形成的关系。方法 应用聚合酶链反应（ＰＣＲ）技术检测６０例健康人和４０例胆囊胆固醇结石患者的Ａｐｏ Ｅ基因多态性及等位基因频率。结果 胆囊胆固醇结石患者Ａｐｏ Ｅ基因型Ｅ３／４的频率２３％（９／４０）明显高于健康对照组７％（４／６０）（Ｐ〈０．０５）,胆囊胆固醇结石患者组ε４等位基因频率为１５％（１２／８０）,明显高     

PDZK1敲除对小鼠肝脏胆固醇代谢和胆囊结石形成影响的实验研究

目的探讨敲除PDZK1(Postsynaptic density-95,disks-large,ZO-1-domain K1,PDZK1)基因对小鼠肝脏胆固醇代谢调节和胆囊结石形成的影响。方法雄性成年PDZK1基因敲除小鼠(PDZK1 knockout,KO组)和野生型小鼠(wild type,WT组),每组各10只,以成石饲料分别喂养4周,观察胆囊成石情况,并收集肝脏和胆囊组织。采用蛋白印迹法测定肝脏PDZK1和清道夫受体B族1型(scavenger receptor B type 1,SRB1)表达。采用胆总管插管收集肝胆汁,测定胆汁分泌率和胆汁胆固醇含量。采用试剂盒酶法测定胆囊胆汁成分并计算胆汁胆固醇饱和指数(cholesterol saturation index,CSI)。以实时定量PCR检测肝脏脂质代谢相关基因的mRNA表达。结果成石饲料喂养4周后,WT组小鼠全部成石(10/10),KO组小鼠则为40%(4/10)成石。两组小鼠肝胆汁分泌率差异无统计学意义,但KO组小鼠肝胆汁胆固醇含量显著降低(P0.05),胆汁酸含量增加(P0.05),且CSI降低(P0.05)。KO组小鼠肝脏SRB1蛋白表达降低(P0.05),甾醇氧-酰基转移酶基因1/2mRNA表达降低(P0.05),而肝型脂肪酸结合蛋白1和胆汁酸转运相关蛋白(ATP结合盒b11)表达则显著增加(P0.05)。结论 PDZK1影响SRB1在小鼠肝脏中表达,降低对高密度脂蛋白胆固醇摄取,减少胆汁胆固醇分泌,继而降低胆囊结石形成。     

Alcohol protects against cholesterol gallstone formation.

Epidemiologic studies have suggested that alcohol intake may protect against cholelithiasis. Gallstone formation was studied in 20 prairie dogs fed a 0.4% cholesterol-supplemented liquid diet. In ten animals, ethanol provided 35% of total calories. In ten pair-fed controls, ethanol was replaced with isocaloric maltose. After 3 months the gallbladders were inspected for gallstones, and gallbladder bile was analyzed. Cholesterol macroaggregates were present in all controls and pigment concretions were noted in five. No stones were observed in ethanol-fed animals. Bile in the ethanol group contained less cholesterol than the controls (5.60 +/- 0.71 vs. 9.16 +/- 0.61 mmol/L, p less than 0.05) while phospholipids, total bile acids, and bilirubin were unchanged. The resulting cholesterol saturation index was reduced in the ethanol group (0.81 vs. 1.22, p less than 0.05). The ratios of trihydroxy to dihydroxy bile acids were also different (2.07 +/- 0.25 in ETOH vs. 3.29 in controls, p less than 0.05). The bile calcium concentration was higher in control animals presumably secondary to the use of complex sugars (5.36 +/- 0.37 vs. 3.77 +/- 0.32 mmol/L, p less than 0.05). These results confirm that ethanol inhibits cholesterol gallstone formation. They further suggest that this effect is dependent on reductions of biliary cholesterol and selective changes in bile acid concentrations.