不同中药对豚鼠胆色素结石模型的生化学影响

目的：观察中药清胆胶囊和养肝利胆颗粒对豚鼠胆囊胆色素结石模型的生化学影响。方法：雄性豚鼠皮下注射林可霉素建立胆色素结石模型,并设立空白组、模型组、清胆胶囊干预组和养肝利胆颗粒干预组,观察各组动物的成石率、胆汁中总胆红素（total bilirubin,TBIL）、游离胆红素（unconjugated bilirubin,UCB）和钙离子浓度等指标的变化。结果：与模型组比较,清胆胶囊组和养肝利胆颗粒组成石率均显著降低（P〈0.01）,胆汁中总胆红素、游离胆红素和钙离子浓度也明显降低（P〈0.05,P〈0.01）。结论：清胆胶囊和养肝利胆颗粒可通过降低胆汁中总胆红素、游离胆红素和钙离子含量而逆转成石胆汁,起到预防胆色素结石形成的作用。     

养肝利胆颗粒对豚鼠胆囊胆固醇结石成石率和血浆胆囊收缩素含量的影响

目的：探讨养肝利胆颗粒对豚鼠胆囊胆固醇结石成石率和血浆胆囊收缩素含量的影响。 方法：80只豚鼠随机分为正常组、模型组、养肝利胆颗粒组和熊去氧胆酸（ursodeoxycholic acid．UDCA）组。除正常组外。采用高胆固醇致石食饵诱发法建立豚鼠胆结石动物模型，并于造模当天开始灌胃治疗，养肝利胆颗粒组予养肝利胆颗粒1．81g／（kg·d），UDCA组予UDCA30．12mg／（kg·d），模型组和正常对照组灌胃等容量的生理盐水，连续7周。疗程结束后观察各组豚鼠一般情况变化和胆囊成石率，并用放射免疫法检测血浆胆囊收缩素（cholecystokinin，CCK）的含量。 结果：养肝利胆颗粒能明显改善胆结石豚鼠的一般情况及行为学体征，但不能恢复到正常水平。模型组豚鼠成石率（82．35％）明显高于正常对照组（5．26％）（P〈0．01），养肝利胆颗粒组和UDCA组豚鼠成石率分别为27．78％和38．89％，均明显低于模型组（P〈0．05）。模型组血浆CCK含量较正常对照组明显降低（P〈0．01）．养肝利胆颗粒组和UDCA组血浆CCK含量虽低于正常对照组，但均高于模型组，差异有统计学意义（P〈0．01）。养肝利胆颗粒组和UDCA组血浆CCK含量比较差异无统计学意义（P〉0．05）。 结论：养肝利胆颗粒能显著降低豚鼠胆结石的成石率，其作用机制可能与养肝利胆颗粒能提高豚鼠血浆CCK含量有关。     

疏肝利胆颗粒对胆管结石术后胆汁成分的影响

目的 :研究疏肝利胆颗粒对胆总管结石患者术后胆汁成分的影响。方法 :选取72例因胆总管结石行胆总管切开取石、T管引流手术患者,随机分为对照组和观察组各36例。对照组给予常规补液、抗感染等处理。观察组在此基础上,术后第2天给予胆汁回输,疏肝利胆颗粒每日1剂口服。总疗程28 d。每日记录胆汁引流量,分别于术中及服中药后7 d、14 d、28 d留取新鲜胆汁,检测胆汁总胆红素(TBIL)、非结合胆红素(UCB)、胆汁酸(TBA)、胆固醇(CHO)、磷脂(PL)、钙离子(Ca~(2+))浓度。结果 :观察组患者术后胆汁引流量明显高于对照组,差异有统计学意义(P<0.05)。观察组患者术后胆汁TBIL、UCB、CHO、Ca~(2+)下降较对照组明显,差异有统计学意义(P<0.05),胆汁TBA、PL升高较对照组明显,差异有统计学意义(P<0.05)。结论:疏肝利胆颗粒可以明显增加胆汁排出量,增加胆汁中总胆红素的排出,提高胆汁酸和磷脂的浓度,使胆汁趋向正常,从而降低胆汁成石性,对防治术后结石复发有一定作用。     

胆汁中胆固醇和胆红素含量相关性研究

为了探讨胆汁中胆固醇和胆红素共同沉淀成石的规律,本文对胆汁中胆固醇和胆红素含量进行相关性分析。观察胆红素的参数为:总胆红素量(TB)、直接胆红素量(CB)、游离胆红素量(UCB)和游离胆红素百分比(UCB％);而观察胆固醇系的参数为:胆固醇量(Ch)、磷脂量(PL)、总胆盐量(BS)及成石指数(LI)。结果在组间对照研究中发现致石胆汁(70例)中UCB％和LI呈明显负相关,而非致石胆汁(8例)中无此现象。在同组对照研究申发现,当致石胆汁逆转为非致石胆汁后,UCB％和LI间原存的负相关关系随之消失。作者提出“空格占位“论对此作出解释。     

胆汁泡蛋白酶联免疫吸附检测法的建立与初步临床应用

目的　建立胆汁泡蛋白快速检测法 ,作为防治胆石症临床研究的指标。方法　提取 3 3 .5kd胆汁泡蛋白 ,建立酶联免疫吸附检测法 (ELISA)标准曲线 ,并应用ELISA药盒测定正常人、胆石症患者胆汁和血清中泡蛋白含量 ,同时观察利胆冲剂、胆通胶囊等对泡蛋白的影响。结果　ELISA曲线方程为Y =0 .0 3 5X(r=0 .99) ;胆固醇性结石组胆囊胆汁和血清 3 3 .5kd泡蛋白含量分别为 (2 13 .4± 70 .1)mg/L、(179.8± 97.9)mg/L ,明显高于胆色素性结石症、非胆石症胆道疾病组以及正常人组 (P <0 .0 5) ,而后三者之间没有显著差异 (P >0 .0 5) ;利胆冲剂治疗两周后 ,胆汁和血清泡蛋白含量显著降低 ,而对照组和胆通胶囊治疗组未见明显变化。结论　胆汁泡蛋白的含量在不同人群差异显著 ;利胆冲剂等药物能降低胆汁和血清 3 3 .5kd泡蛋白含量 ,改变胆汁致石性     

新生儿高未结合胆红素血症的胆汁酸测定的意义

对 2 0例标准肝功能指标正常的新生儿未结合胆红素升高为主的病理性黄疸进行胆汁酸 (TBA)检测 ,结果显示 :高胆组特别是由窒息和 (或 )感染因素所致的TBA较对照组差异有显著性 ,且TBA与总胆红素呈正相关。提示新生儿高未结合胆红素血症特别是窒息和 (或 )感染因素引起者存在肝功能损害及轻度胆汁瘀积 ,TBA可作为监测肝功能的早期指标及胆汁瘀积指标 ,并对指导临床及时护肝、利胆治疗有重要意义     

升清胶囊对豚鼠胆石病相关基因的影响

目的:探讨中药升清胶囊在分子层面防治胆石病的机制.方法:雌性豚鼠60只,随机分成正常组(喂正常饮食作为对照)、模型组(喂低蛋白饮食致石)和中药组(喂低蛋白饮食致石加中药升清胶囊治疗).6周后处死并取材,观察动物成石情况,检测肝组织胆红素尿苷二磷酸葡萄糖醛酸基转移酶(bilirubin UDP-glucuronosyltransferase, B-UGT)mRNA及胆固醇7α羟化酶(cholesterol 7α-hydroxylase, CYP7A1)mRNA表达.结果:各组豚鼠成石比例分别为正常组2/14、模型组为9/11、中药组为4/14,组间有显著差异(P＜0.05),正常组和中药组豚鼠的肝组织B-UGT mRNA及CYP7A1 mRNA表达明显高于模型组(P＜0.05).结论:中药升清胶囊可能是通过上调肝组织中B-UGT mRNA和CYP7A1 mRNA的表达,干预胆红素和胆固醇代谢,抑制致石性胆汁形成,起到预防胆结石的作用.     

3种从肝治胆方对胆石症模型豚鼠的防治作用

目的 观察疏肝理气法、养肝柔肝法和清肝利湿法治疗胆囊结石的疗效。方法 将75只豚鼠随机分为正常组和模型组、疏肝组、养肝组和清肝组,采用喂食高脂致石性饲料和少量蔬菜的方法复制胆石症模型,疏肝组灌服十二味疏肝利胆颗粒,养肝组灌服一贯煎颗粒,清肝组灌服龙胆泻肝颗粒,正常组和模型组均灌胃生理盐水。8周后检测各组豚鼠胆囊结石形成率,结石主要成分,血清丙氨酸氨基转移酶（alanine aminotransferase,ALT）、天冬氨酸氨基转移酶（aspartate aminotransferase,AST）、总胆固醇（total cholesterol,TC）水平,以及胆汁总胆红素（total bilirubin,TBIL）和Ca2+浓度,观察胆囊病理变化。结果 疏肝组、养肝组和清肝组豚鼠胆囊结石形成率较模型组明显降低（P<0.05）,结石主要成分为胆固醇; 与模型组比较,疏肝组、养肝组和清肝组豚鼠胆囊病理变化均明显改善,血清ALT、AST、TC水平均明显降低（P＜0.05）,胆汁TBIL浓度无明显变化（P>0.05）,仅清肝组Ca2+浓度明显下降（P<0.05）;养肝柔肝法降低AST的作用最优（P<0.05）,疏肝理气法降低TC的作用最优（P<0.05）,清肝利湿法降低胆汁Ca2+的作用最优（P<0.05）。结论 疏肝理气法、养肝柔肝法和清肝利湿法均可防治豚鼠胆囊结石形成,3种中医治法的作用存在差异。     

大黄利胆胶囊对胆囊结石患者胆汁成分的影响

目的：探讨大黄利胆胶囊对胆囊结石患者胆汁成分的影响。方法选取河北北方学院附属第二医院2012年12月至2014年11月收治的择期行腹腔镜胆囊结石手术(LC)患者160例,按数表法随机分为观察组与对照组各80例,观察组患者术前两周给予大黄利胆胶囊口服,对照组术前不服用任何药物,观察两组患者胆囊切除术后一般状况,检测两组患者胆汁中结合胆红素、总胆红素、胆固醇和胆汁酸的含量,计算出未结合胆红素(即游离胆红素)占总胆红素百分比(UCB%)。以胆固醇含量(TC)、胆汁酸含量(TBA)和USB%为指标,比较两组之间的差异。结果两组患者术后一般情况比较差异均无统计学意义(P>0.05);观察组患者胆汁中TC、USB%水平分别为(16.14±3.90) mmol/L、(0.139±0.090) mmol/L,对照组分别为(17.66±3.78) mmol/L、(0.187±0.149) mmol/L,观察组TC、USB%明显低于对照组,差异均具有统计学意义(P<0.05);观察组患者胆汁中TBA水平为(119.1±13.5) mmol/L,明显高于对照组的(106.7±10.2) mmol/L,差异具有统计学意义(P<0.05)。结论大黄利胆胶囊可影响胆囊结石患者胆汁成分,对胆囊结石具有良好的治疗和预防作用。     

养肝利胆颗粒对胆固醇结石豚鼠抗胰岛素抵抗的作用

目的：通过观察养肝利胆颗粒对胆囊胆固醇结石豚鼠胰岛素敏感指数的影响,探讨养肝柔肝法防治胆石病的作用机制。方法：选用80只豚鼠,雌雄各半,随机分成正常组、模型组、养肝利胆组和熊去氧胆酸组。建立豚鼠胆囊胆固醇结石动物模型,并予相应的药物干预。各组动物均于第7周末取材,测定胆结石成石率及空腹血糖（FPG）、血胰岛素（FINS）、三酰甘油（TG）、总胆固醇（TC）、游离脂肪酸（FFA）,计算胰岛素敏感指数（ISI）。结果：模型组成石率为83．25％,其成石率显著高于正常组（P〈0．01）。熊去氧胆酸组和养肝利胆组的FPG及FINS水平相对于模型组均有所降低,ISI明显提高（P〈0．01）;养肝利胆组的FPG、FINS均低于熊去氧胆酸组,而ISI高于熊去氧胆酸组（P〈0．05）。熊去氧胆酸组和养肝利胆组的TG、TC、FFA相对于模型组而言均降低,但TG、TC熊去氧胆酸组和模型组之间的差异无显著性（P〉0．05）,养肝利胆组与模型组之间差异具有统计学意义（P〈0．01）,且养肝利胆组明显均低于熊去氧胆酸组（P〈0．05）;FFA两药物组均明显低于模型组（P〈0．01）,但两者之间无差异（P〉0．05）。结论：养肝利胆颗粒能显著降低豚鼠胆固醇结石率,其作用机制可能与降低TG、TC、FFA,改善胆固醇结石豚鼠胰岛素抵抗有关。     

Role of monoconjugated bilirubin in pathogenesis of gallstones.

In order to explore the substantial role of monoconjugated bilirubin (MCB) in gallstone formation, bile pigment precipitation and hemolytic jaundice, three experimental protocols have been studied, namely, (1) MCB and dietary induced pigment gallstone model, (2) MCB in human gallstone and incubated bile precipitates and (3) MCB in hemolytic jaundice. It was found that doubly increased MCB accounted for 1/3 of the total pigment in lithogenic guinea pig and CDCA plus glycine possessed certain protective effect from gallstone development; MCB was found in human gallstones both in bilirubinate and cholesterol type, and an unknown pigment, possibly an isomer of MCB, was found in black stone. During experimental hemolytic jaundice model preparation, both MCB and UCB were elevated, and MCB was found increased by 10 times, even exceeding the concentration of DCB when the injected bilirubin was about 4 mg/kg of body weight. It is reasonable to consider that MCB as a coprecipitant with UCB and a precursor of UCB played an essential role in the pathogenesis of gallstones.

     

Effects of choleretics on bile compositions drained from patients with pigment gallstone

Objective: To provide evidence for three-level prevention of cholelithiasis by means of observing the effects of some choleretics on bile compositions drained from patients with pigment gallstone.Methods: Twenty-seven patients suffering from primary pigment gallstones and having received treatment of choledochostomies plus T-tube or endoscopic nasal bile drainage (ENBD) were divided equally into three UDA group) and combination of LDL and UDA (the LDL UDA group) through oral intake(7 patients in each group). Besides, 6 post-operational patients got no treatment with any drug were allocated in the control group. Bile of all the patients was collected before treatment and on the 1, 3, 5, 7th day after the treatment started to detect levels of total bile acid (TBA), glycocholic acid (GCA), taurocholic acid (TCA), glycocholic cheno-desoxycholic acid (GCDCA), total bilirubin (TBIL), uncombined bilirubin (UCB), concentration of calcium ion (Ca2 ) as well as the bacterio-genetic and endogenous β-glucuronidase activity for comparing.Results: Levels of TBA, GCA, TCA and GCDCA got gradually increased in the UDA group and the LDL UDA group after treatment ( P＜0.05), while those in the LDL group remained unchanged, showing an insignificant difference as compared with those in the control group. In the LDL group and the LDL UDA group, TBIL gradually increased while UCB gradually decreased in the course of treatment ( P＜0.05). Moreover, levels of Ca2 and endogenous β-glucuronidase activity got significantly lowered (P＜0.05). Conclusion: Combined use of LDL and UDA could elevate levels of TBA, GCA, TCA, GCDCA, enhance the excretion of TBIL in patients with pigment gallstone after bile drainage, lower levels of UCB and Ca2 and the activity of endogenous β-glucuronidase in the bile, so as to reduce the possibility of stone formation of bile, and therefore, it could be used to prevent the production of pigment gallstone, especially to prevent post-operative recurrence of stones.     

Effects of gastrointestinal peptides on formation of gallstone in guinea pigs.

In light of the effects of gastrointestinal (GI) peptides on bile secretion and biliary tract mobility, we studied the effects of GI peptides on gallstone formation in guinea pigs fed on low protein lithogenic diet. The peptides under study included cholecystokinin octapeptide (CCK-8), vasoactive intestinal peptide (VIP), somatostatin (SRIF), secretin (SEC), and neurotensin (NT). Hepatic bile flow, electrolytes, and other bile components were also measured. It was found that CCK-8 and VIP suppressed the formation of gallstones and increased hepatic bile flow and Na+, K+, Cl- output significantly. On the other hand, SRIF significantly promoted gallstone formation. The rates of gallstone formation in CCK-8, VIP, and SRIF treated guinea pigs were 15.4%, 23.5%, and 88.0%, respectively, in contrast to 56.8% in the control group. The inhibitory effect of CCK-8 and promoting effect of SRIF on gallstone formation were dose-dependent.

     

综合模拟胆汁体系中未结合胆红素的热力学研究及其临床价值

目的 在Admirand-Small胆汁体系基础上建立-含有未结合胆红素(UCB)的综合模拟体系及其数学模型,并探讨其临床价值。方法 研究胆汁中磷脂、胆盐、胆固醇以及总脂浓度等综合因素对UCB溶解的影响,获得在总脂浓度不一、胆固醇饱和指数(CSI)同时变化的综合模拟胆汁中UCB饱和溶解度的数学表达式,并建立描述UCB致石指数(UCB Lithogenic Index,ULI),评估其临床意义。结果 UCB饱和溶解度值与CSI、磷脂／胆盐 磷脂以及总脂浓度呈有固定的数学关系;临床上胆石症与非胆石症患者胆汁的ULI有显著差异。结论 UCB与胆固醇的溶解、沉淀(热力学)相互影响,考察UCB饱和溶解的指标能判别致石胆汁与非致石胆汁。     

"BILIRUBIN-CALCIUM COMPOUND" PRECIPITATION AND THE EFFECT OF BILE SALTS ON IT THE PATHOGENESIS OF PIGMENT GALLSTONE

The formation of insoluble "bilirubin-calcium compound" followed the principles of solubility pro- duct, i.e. (UCB). (Ca2+)2=Ks' (conditional equili brium constant). When the concentration of cholate exceeded l mM, it would combine with calcium to form a soluble compound, resulting in a decrease of calcium ion concentration. This reaction was rever sible and might be helpful in stabilizing the calcium ion concentration. There was a negative correlation between the concentration of cholic acid and calcium ion and also between the cholic acid concentration and the ratio of ionized calcium to total calcium in 41 samples of human bile. The cholic acid concen tration in bile of gallstone patients was lower and the calcium ion cortcentration was higher than those in bile of controls. Besides, the micella of bile salts might be able to enclose and isolate the unconjugated bilirubin (UCB) partially from calcium ion. Thus, the formation of "bilirubin-calcium compound" precipi. tate was inhibited. Study on the effect of eight bile components, i.e. UCB, bile salts, calcium, magnesium, pH, lecithin, cholesterol, and glycoprotein on the precipitation of bilirubin in imitating bile revealed that the higher the cholate or cholesterol concentration in imitating bile, the less the bilirubin in precipitate; and the more the other components in bile, the more the bilirubin in precipitate. Regression equation was established be tween these bile components and the amount of bili rubin in precipitate, suggesting that the discriminant distinguishing the lithogenic bile from nonlithogenic one might be a polyfactor function. A function in cluding UCB, total calcium, and bile salts was used iri 16 samples of human choledochal bile to predict lithogenic ability, a coincident rate being 81.3'70. Using this function, we would be able to investigate the effect of bile components on pigment gallstone formation both qualitatively and quantitatively.     

腹腔镜和开腹胆囊切除术对患者肝功能及C反应蛋白水平的影响

目的探讨腹腔镜胆囊切除术(LC)和开腹胆囊切除术(OC)对患者肝功能和C反应蛋白(CRP)水平的影响。方法将120慢性胆囊炎并胆囊结石症及急性结石性胆囊炎患者随机分为LC组(69例)和OC组(51例),比较两组手术前后血清总胆汁酸(TBA)、血清总胆红素(TBIL)、丙氨酸氨基转移酶(ALT)、γ谷氨酸转肽酶、碱性磷酸酶、天冬氨酸氨基转移酶(AST)以及CRP的变化。结果两组患者治疗后TBA、TBIL、ALT、AST及CRP变化趋势相同,两组不同时间点比较差异有统计学意义(P<0.05),组间比较差异有统计学意义(P<0.05)。结论 LC对机体损伤较开腹切除小,对肝功能的影响无明显差异,是一种安全可行的手术方式。     

RELATIONSHIP BETWEEN DIET AND GALLSTONES IN HAMSTERS

The present study aimed at the induction of cholesterol stones (Ch S) in young hamsters with a diet rich in refined carbohydrate and animal fats, and that of pigment stones (P S) in adult hamsters with a low protein diet. After four weeks of feeding according to the above-mentioned protocol, the rate of gallstone formation in the Ch S and P S groups were 81.56% and 89.77% respectively, while those of the control groups were 20% and 40% (P<0.001). Eight weeks after switching back to normal diet, the amount of gallstones in both experimental groups decreased significantly; in some animals, the stones disappeared completely. The ratio of cholesterol/bilirubin in stones of the Ch S group is three times that of the control group, and the same ratio in atones of the P S group is 47% that of the control. During the period of stone formation, the bile of the Ch S group was supersaturated with cholesterol, while unconjugated bilirubin increased significantly in the bile of the P S group. There was a general decline in different bile acids in bile of both groups. During the later period of stone dissolution, the bile components of both lithogenic groups tended to become normal, but glycocholic acid alone increased greatly. The result suggests that the type of diet is closely related to the formation and dissolution of gallstones. It has also been demonstrated that the lithogenic tendency of the bile can be reversed and gallstones dissolved in the early stage of their formation.