养肝利胆颗粒对胆色素结石炎症反应环节的影响

[目的]观察养肝利胆颗粒（YGLD）对豚鼠胆色素结石形成过程中炎症环节的影响。[方法]应用雄性豚鼠皮下注射林可霉素联合喂养致石饲料建立胆色素结石模型,观察YGLD对该模型成石率、胆囊容积、胆汁中黏蛋白及C反应蛋白（CRP）浓度的影响。[结果]YGLD组与模型组比较成石率显著降低（P〈0．01）,胆囊容积明显减小（P〈0．05）,胆汁中黏蛋白及CRP浓度明显降低（P〈0．05）。[结论]YGLD通过降低胆汁中黏蛋白、CRP水平来发挥逆转成石胆汁及降低胆色素结石成石率的重要作用。     

茵陈利胆颗粒对结石性胆囊炎的作用

茵陈利胆颗粒由茵陈、黄芩、柴胡等中药组成,具有清热利湿、疏肝利胆之功效.主要针对饮食肥甘所伤或湿热入侵而致者,以湿热为主,即为慢性胆囊炎急性发作为主要临床表现者.1 材料与方法1.1 材料1.1.1 动物 豚鼠,雌雄各半,体重300～ 350 g,合格证号:(吉)2003 - 0001.由吉林大学基础医学院动物实验中心提供.试验前先将动物放人实验室适应2～3d,自由进食进水,室内温度维持在22℃左右,湿度维持在55％左右,动物室每天保持12h照明.1.1.2 药品 茵陈利胆颗粒,由吉林大学基础医学院药化室提供,批号:20060121.利胆止痛片,由云南白药集团股份有限公司出品,批号:20051207.     

清胆胶囊对胆固醇结石小鼠肝脏中PPAR-γ、CYP7A1及NF-κB表达的影响

[目的]观察清胆胶囊对胆固醇结石小鼠肝脏过氧化物酶体增殖物激活受体(PPAR)-γ、胆固醇7α-羟化酶(CYP7A1)及核因子(NF)-κB表达的影响。[方法]38只C57BL/6雌性小鼠随机分为正常对照组(n=10)、模型组(n=15)和清胆胶囊组(n=13)。除正常对照组外,模型组和清胆胶囊组小鼠采用高脂饮食诱发法建立胆固醇结石模型。造模过程中,清胆胶囊组小鼠予清胆胶囊0.36 g/(kg.d)灌胃治疗。8周后观察各组小鼠的成石率,并用Western Blotting法检测肝脏中PPAR-γ、CYP7A1及NF-κB的表达。[结果]清胆胶囊组成石率显著降低(P0.01),小鼠肝脏PPARγ及CYP7A1表达增强,NF-κB表达降低。[结论]清胆胶囊可通过增强肝脏PPARγ及CYP7A1的表达,抑制NF-κB核转位来发挥防治胆固醇结石的作用。     

易成石和抗成石小鼠肝脏胆固醇代谢调节酶的基因表达特征

目的通过研究胆囊胆固醇结石易成石小鼠(C57L鼠)和抗成石小鼠(AKR鼠)肝脏胆固醇代谢调节酶的基因表达差异来探讨胆囊胆固醇结石形成的分子机制.方法用致石饲料(含15%脂肪、1.25%胆固醇和0.5%胆酸)喂养C57L和AKR鼠4周,分别在喂养前、后检查其肝脏重量、肝脏胆固醇含量和胆囊内结石形成情况,并用RT-PCR法分析参与肝脏胆固醇代谢调节的肝脏3羟基3甲基-戊二酰辅酶A还原酶(HMG-CoAR)、胆固醇7α羟化酶(C7H)、乙酰基辅酶A-胆固醇酰基转移酶(ACAT)和低密度脂蛋白受体(LDLR)的mRNA含量.结果致石饲料喂养前、后AKR鼠肝脏胆固醇含量均明显高于C57L鼠,致石饲料诱导4周后C57L鼠胆囊内有胆固醇结石形成,而AKR鼠则无.致石饲料诱导前AKR鼠肝脏HMG-CoAR的mRNA表达水平明显高于C57L鼠,而ACAT、LDLR、C7H的mRNA水平在两组小鼠间差异无统计学意义(P＞0.05).致石饲料诱导后,AKR鼠肝脏HMG-CoAR和C7H的mRNA水平分别下降31%和30%,但C57L鼠无明显改变,其中AKR和C57L鼠肝脏LDLR的mRNA表达水平则分别提高14%和41%.结论致石饲料作为一种环境因素能揭示C57L和AKR鼠肝脏胆固醇代谢调节酶的基因表达特征.致石饲料诱导后C57L鼠肝脏HMGCoAR基因表达水平的下调不足和LDLR基因表达水平的显著上升可能在其胆囊胆固醇结石形成过程中发挥着一定作用.     

蜂胶对小鼠体内胆固醇逆转运的影响

目的 观察蜂胶干预后小鼠血浆、肝脏、粪便、肾上腺中3H-胆固醇的分布和血浆脂质水平的变化,探讨蜂胶对小鼠体内胆固醇逆转运的影响.方法 14只C57BL/6小鼠随机分为对照组和蜂胶组,分别给予单纯溶剂和蜂胶灌胃4周后,腹腔注射经乙酰化低密度脂蛋白及3H-胆固醇处理过的小鼠巨噬细胞悬液,单独笼养48 h,取血,留置肝脏和肾上腺,收集粪便.酶法测定血浆脂质水平;经液体闪烁计数测定血浆、肝脏、粪便、肾上腺中的3H-胆固醇含量.结果 与对照组相比,蜂胶升高血浆高密度脂蛋白胆固醇和总胆固醇水平分别为39%和29%,对低密度脂蛋白-胆固醇和甘油三酯的水平影响不大;注入细胞后血浆3H-胆固醇分布明显的迅速增高,6 h为对照组2.9倍,24 h为对照组1.7倍;肝脏中3H-胆固醇分布降低了39%;粪便中的3H-胆固醇分布降低了60%;而小鼠肾上腺中3H-胆固醇的分布升高了84%.结论 蜂胶在体内促进了外周巨噬细胞中多余的胆固醇的流出和肾上腺组织的利用.     

养肝益水颗粒对高血压病早期肾损害动态血压的影响

目的 观察养肝益水颗粒对高血压病早期肾损害患者24 h动态血压的影响.方法 选择80例高血压病早期肾损害患者,随机分为治疗组和对照组.两组均给予常规降压治疗.治疗组同时加服养肝益水颗粒.两组疗程均为4周.分别于治疗前和治疗4周后进行24 h动态血压检查.结果 对照组有1例中途要求退出观察,另1例因自行停药而剔除;治疗组有1例因故失访而剔除;两组降压疗效分别为78.95%与84.62%(P>0.05),治疗组与对照组相比,治疗后杓型血压比例明显增加,反杓型血压明显减少(P<0.01).结论 养肝益水颗粒治疗高血压病早期肾损害符合中医辨证特点,对高血压病早期肾损害患者动态血压昼夜节律有一定的调节作用.     

高胆固醇饮食对小鼠肝脏内皮脂酶mRNA表达的影响

目的内皮脂酶（endothelial lipase，EL）是新近发现的一种脂肪酶，它与肝脂肪酶（HL）、脂蛋白脂肪酶同属于甘油三酯脂肪酶基因家族，参与高密度脂蛋白（HDL）的代谢。本研究旨在观察高胆固醇饮食对小鼠肝脏EL mRNA表达的影响，并同时检测小鼠血脂水平的改变，研究EL mRNA表达水平与血脂的关系。     

小肠动力障碍对胆固醇结石形成影响的研究进展

小肠动力障碍及小肠移行性复合运动(migrating motor complex,MMC)减弱对胆固醇结石形成的影响作用日益受到重视。小肠动力障碍及MMC减弱间接地使胆汁中脱氧胆酸(deoxycholic acid,DCA)浓度增高:DCA本身可以使肠转运减慢,肠道吸收胆固醇增加,胆汁中DCA比例过高直接抑制胆囊运动;DCA增强胆汁中胆固醇分泌;DCA增加富含胆固醇的“泡”(vesicles)不稳定性,增强胆汁胆固醇结晶形成。胆汁中DCA浓度增高,胆汁酸减少,胆囊运动减弱,从而促进胆固醇结石的形成。     

胆囊胆固醇结石患者肝脏受体类似物1基因表达差异的研究

目的研究胆囊胆固醇结石患者肝脏受体类似物1(LRH-1)表达,探讨其与胆固醇结石病发病的关系。方法27例胆囊胆固醇结石患者,男6例,女21例,平均年龄52．44岁。14例无胆石症者为对照(肝脏肿瘤2例,胆囊息肉患者12例),男9例,女5例,平均年龄47．50岁。测定胆汁脂类成分和计算胆汁胆固醇饱和指数。实时定量PCR法测定肝脏LRH-1 mRNA的表达量。结果胆石组LRH-1表达14．18±9．37,高于对照组7．86±6．19,(P＜0．05),胆石组胆汁呈胆固醇过饱和(1．17±0．27)。结论本研究提示肝脏LRH-1表达增高与胆囊胆固醇结石病有关。     

胆固醇结石的分类及声像图观察

本文应用Ｂ型超声对２５例胆囊结石的病人术前反复多次检查，初步定性诊断，手术取出结石经红外吸收光谱确定为胆固醇结石，切片放在偏光显微镜下观察内部结构，根据不同的内部结构，将胆固醇结石分成三种类型四个亚型，并探讨各自的声像图特征。结果表明，结石因内部结构不同，声像图表现亦不相同。     

胆囊胆固醇结石形成相关的候选基因研究进展

胆囊胆固醇结石病是一种常见疾病。近年来研究证实它的形成涉及环境变化和多基因的相互作用,遗传因素涉及的候选基因可以分为六大类,此文对其主要候选基因的研究进展作一综述。     

Effects of sphingolipid synthesis inhibition on cholesterol gallstone formation in C57BL/6J mice

Background: Sphingolipids play a very important role in cell membrane formation, signal transduction and plasma lipoprotein metabolism. The first rate‐limiting step in the sphingolipid biosynthetic pathway is catalyzed by serine palmitoyltransferase (SPT), and myriocin is a potent and specific inhibitor of SPT. We investigated the impact of SPT inhibition on cholesterol gallstone formation in C57BL/6J mice. Methods: Three groups of eight‐week‐old C57BL/6J mice were utilized. Each group consisted of 20 mice; group A, B, and C were fed normal chow, lithogenic diet with phosphate buffered saline, and lithogenic diet with myriocin (0.3 mg/kg), respectively, for 6 weeks. The ceramide levels in both serum and bile were assessed by high performance liquid chromatography analysis. Protein expression of ERK, JNK and p38 in the extracted gallbladder were determined by Western‐blot analysis. Results: Myriocin treatment caused a significant decrease in the rate of cholesterol gallstone formation. The lithogenic diet mice (group B) showed the highest ceramide activities in both the serum and bile among all the tested groups and there was significant suppression of the ceramide levels in both the serum and bile of the myriocin‐treated mice (group C, p < 0.05). Phosphorylation of p38 in the gallbladder was increased in the lithogenic‐diet mice and the expression of phosphorylated p38 was significantly suppressed in the myriocin treated mice. Conclusions: SPT inhibition by myriocin suppressed gallstone formation and the levels of ceramide in both the serum and bile. p38 in the cellular signaling pathways might be associated with cholesterol gallstone formation.     

Apolipoprotein AI-CIII-AIV gene cluster polymorphisms in relation to cholesterol gallstone

OBJECTIVE: To investigate the frequency of variants at Xmn I, Msp I sites of apolipoprotein (Apo), A I‐CIII‐AIV gene cluster, and its relation to cholesterol gallstones in Chinese patients. METHODS: Restriction fragment length polymorphisms (RFLP) at Xmn I, Msp I sites of ApoAI‐CIII‐AIV gene cluster were studied using a polymerase chain reaction (PCR) in 161 patients with cholesterol gallstones and 94 healthy subjects from a Chinese population in Sichuan Province. RESULTS: In both the cholesterol gallstone group and the healthy control group, X1 and M1 alleles were the major alleles and homozygous X₁X₁ and M₁M₁ genotypes were the most frequent. However, the frequency of X2 allele mutation in female patients of the cholesterol gallstones group was significantly higher than that in women in the healthy control group (P < 0.05), but no difference was found in the frequency of M2 alleles mutation (P > 0.05). CONCLUSION: The data showed that Xmn I RFLP of ApoAI‐CIII‐AIV gene cluster is associated to some extent with cholesterol gallstones in female Chinese patients.     

Bile acids in serum and bile of patients with cholesterol gallstone

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Increased bile acid concentration in liver tissue with cholesterol gallstone disease

Patients with cholesterol gallstone disease have a reduced pool of bile acids. Overly sensitive feedback inhibition of bile acid synthesis has been postulated to explain this size reduction. To test this hypothesis, hepatic bile acid concentration and the activity of cholesterol 7-hydroxylase, the rate-limiting enzyme for bile acid biosynthesis, were determined in ten patients with cholesterol gallstones and ten patients without gallstones. The bile acids present in liver tissue are the sum of those returning to liver and those newly synthesized in liver. If an overly sensitive feedback inhibition truly existed in our gallstone patients, a decreased concentration of hepatic bile acids would have been expected. However, patients with cholesterol gallstones had significantly higher total (143.3 ±25.5 vs 64.5±10.8 nmol/g liver,P<0.01), chenodeoxycholic=" (64.1±9.9=" vs=">P<0.01), deoxycholic=" (22.8±10.9=" vs=">P<0.05), and=" ursodeoxycholic=" acid=" (6.2±1.4=" vs=">P<0.01) concentrations=" than=" patients=" without=" gallstones.=" the=" activity=" of=" cholesterol=">-hydroxylase did not differ significantly between the two groups. Impaired hepatic transport or secretion of bile acids is strongly suspected in cholesterol gallstone patients. The findings of the present study showed no evidence of overly sensitive feedback inhibition of bile acid synthesis in cholesterol gallstone patients. Bile acid pool size may be affected by the inappropriate increase of hepatic bile acids rather than by overly sensitive feedback inhibition.