清胆胶囊与养肝利胆颗粒对豚鼠胆色素结石炎症反应环节的影响

目的：观察两种不同治则的中药清胆胶囊和养肝利胆颗粒对豚鼠胆色素结石形成过程中炎症环节的影响。方法：应用雄性豚鼠建立胆色素结石模型,分别观察清胆胶囊和养肝利胆颗粒对该模型成石率、胆囊容积、胆汁中黏蛋白浓度及C反应蛋白（CRP）浓度等指标的影响。结果：清胆胶囊组与养肝利胆颗粒组成石率均显著降低（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）,两种中药制剂对黏蛋白及CRP的影响无统计学意义。结论：清胆胶囊与养肝利胆颗粒对胆色素结石有良好的防治作用,而且二者在干预胆色素结石病炎症反应环节上的作用效果和机制基本相似。     

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。     

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。     

清胆胶囊对胆色素结石豚鼠胆汁中CRP及黏蛋白含量的影响

目的:观察清胆胶囊对胆色素结石豚鼠胆汁中CRP及黏蛋白含量的影响。方法:应用雄性豚鼠建立胆色素结石模型,观察清胆胶囊对其成石率、胆囊容积、胆汁中黏蛋白及C反应蛋白等指标的影响。结果:清胆胶囊组成石率显著降低(P<0.01),胆囊容积明显减小(P<0.05),胆汁中黏蛋白及C反应蛋白明显降低(P<0.05)。结论:清胆胶囊可降低成石胆汁中黏蛋白、C反应蛋白含量,从而发挥逆转成石胆汁及降低结石成石率的作用。     

大柴胡颗粒对胆色素结石豚鼠的保护作用

目的 观察大柴胡颗粒对胆色素结石豚鼠的保护作用。方法 将豚鼠随机分为对照组,模型组,大柴胡颗粒高、中、低剂量（4.4、2.2、1.1 g/kg）组和熊去氧胆酸（50 mg/kg）组。采用饲料法复制胆色素结石豚鼠模型,观察大柴胡颗粒对胆色素结石豚鼠的成石率、血清天冬氨酸转氨酶（AST）、丙氨酸转氨酶（ALT）、碱性磷酸酶（AKP）、谷氨酰基转移酶（γ-GT）、总胆红素（TB）、1分钟胆红素水平、血浆和胆囊组织胃动素和生长抑素（SS）水平,以及胆汁内总胆酸（TBA）、磷脂、总胆固醇（TC）、黏蛋白量的影响;肝脏和胆囊组织进行HE染色,观察其组织病变情况。结果 大柴胡颗粒中剂量组可显著降低结石成石率;其3个剂量组均可降低胆囊SS水平;其中、高剂量组可显著升高血浆和胆囊胃动素水平,降低血清γ-GT、1分钟胆红素水平和胆汁黏蛋白的量;其高剂量组可显著降低血清AST和TB、血浆SS和胆汁中TC水平,升高胆汁中TBA的量;而低剂量组可显著升高胆汁中磷脂的量,与模型组比较差异显著（P＜0.05、0.01）。组织病理学观察表明大柴胡颗粒可显著改善胆囊上皮增生,减轻组织水肿、炎细胞浸润、肝脏脂肪变性、汇管区炎细胞浸润和纤维组织增生。结论 大柴胡颗粒对胆色素结石豚鼠具有一定的保护作用,该作用可能与其减少肝胆细胞损伤、调节胆汁成分、促进胆汁分泌等机制相关。     

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。     

养肝柔肝法逆转豚鼠成石胆汁致石性的实验研究

目的　探讨养肝柔肝中药养肝利胆颗粒剂逆转成石胆汁致石性的机制。方法　将 6 0只豚鼠随机分为正常组、模型组、治疗组 ,每组 2 0只。分别喂食正常饲料、致石饲料、致石饲料加养肝利胆颗粒 ,4周后处死取材 ,检测胆囊成石率、胆汁总胆汁酸 (TBA)、胆汁总胆红素 (TBIL)、胆汁结合胆红素 (CB)、胆汁非结合胆红素 (UCB)、胆汁钙离子 ,并进行胆汁胆红素组分HPLC分析。结果　 (1)正常组成石率为 5 % ,模型组为 81.2 5 % ,治疗组为 31.2 5 % (P <0 .0 5 )。 (2 )模型组胆囊胆汁中TBIL、CB、UCB及Ca2 + 均高于治疗组及正常组 ,TBA低于正常组 ,治疗组TBA低于正常组 ,Ca2 + 高于正常组 (P <0 .0 5 )。(3)模型组单结合胆红素 (MCB)值高于治疗组及正常组 ,双结合胆红素 (DCB)低于治疗组及正常组 (P <0 .0 1) ,治疗组DCB值低于正常组 ,各组UCB的完整峰面积 (IPA)值无明显区别。 (4)模型组的MCB百分比和UCB百分比高于治疗组及正常组 ,DCB百分比低于治疗组及正常组 (P <0 .0 5 ) ,治疗组的MCB百分比也高于正常组 ,同时DCB低于正常组。结论　养肝柔肝中药能显著降低豚鼠胆囊色素性结石的成石率 ,有明显逆转胆汁致石性的作用     

金钱对唑合剂防治胆石症的实验研究

目的观察中药经验方金钱对唑合剂对胆色素结石的预防与治疗作用,为胆石症的治疗提供依据。方法采用豚鼠胆色素结石模型,观察胆囊形状、成石率、胆汁量,并进行胆汁和血清的生化测定。结果金钱对唑合剂三剂量组与模型组比较,胆囊成石率、胆汁量、总胆红素含量、总胆汁酸含量有显著性差异,而直接胆红素含量和总胆固醇、甘油三酯、高密度脂蛋白的含量差异无显著意义。结论表明金钱对唑合剂能显著降低豚鼠胆结石的发生率;能明显促进豚鼠胆汁的分泌;有调节胆汁成分的作用;但对血脂成分无明显的影响。     

小柴胡汤加减方对胆道术后患者胆汁成分及成石趋势的影响

目的：观察小柴胡汤加减方对胆道术后患者胆汁成分及成石趋势的影响。方法：采用随机对照的临床试验方法,将31名符合胆囊结石合并胆总管结石诊断的患者,分成两组。中药组：口服小柴胡汤加减方,制成中药制剂包50mL于术后第1周开始,给予早、晚中药制剂包各1包,连续30日;对照组：不服利胆药物,仅按胆道术后常规处理。运用生化分析仪分别于术中、术后第1周、第3周、第5周检测胆汁成分。结果 ：中药组在胆汁代谢方面相对于对照组能够提高胆汁酸含量,术后第3周、第5周有显著差异（P〈0.01）;能够降低总胆红素及游离胆红素含量,相对于对照组术后第3周有统计学意义（P〈0.05）,术后第5周有显著差异（P〈0.01）。结论：本研究证实小柴胡汤加减方能够有效调节胆汁中胆固醇、胆汁酸、磷脂的含量及比例,从而抑制胆石的形成,这可能是小柴胡汤加减方防止胆石形成、发展的主要机制之一;小柴胡汤加减方对胆红素的代谢具有明显的调节作用,可能与其调节内源性及外源性β-葡萄糖醛酸苷酶（β-Gase）,减少游离胆红素含量,从而抑制胆色素结石的发生及发展有关。     

升清胶囊下调胆囊结石豚鼠胆囊上皮组织雌、孕激素受体

目的：研究雌激素受体和孕激素受体在胆固醇结石形成中的作用及升清胶囊对其表达的影响。方法：将80只雌性豚鼠随机分为正常对照组、模型组、熊去氧胆酸组和升清胶囊组,每组20只。除正常对照组外,采用高脂致石饮食法建立胆囊胆固醇结石模型。升清胶囊组和熊去氧胆酸组豚鼠分别灌胃相应药物。造模7周后观察各组豚鼠胆囊成石情况,并采用免疫组织化学法检测豚鼠胆囊上皮组织雌、孕激素受体的表达。结果：升清胶囊可降低造模豚鼠的成石率,与模型组比较,差异有统计学意义（P〈0.05）。按正常对照组、升清胶囊组、熊去氧胆酸组和模型组的顺序,各组豚鼠胆囊组织雌、孕激素受体阳性表达半定量分级逐级升高,升清胶囊组与模型组、熊去氧胆酸组比较差异有统计学意义（P〈0.05）。各组间雌、孕激素受体阳性表达率比较,差异有统计学意义（P〈0.05）。结论：疏肝利胆方药升清胶囊可下调雌、孕激素受体的表达,降低胆固醇结石形成。     

无菌豚鼠形成胆色素结石的动物模型

无菌豚鼠胆囊结石诱发率很高。胆囊结石和胆囊胆汁成份分析表明,无菌豚鼠胆囊内产生的结石为色素型结石,其胆汁特征与人色素型结石类同,提示无菌豚鼠可作为研究胆色素类结石的实验动物模型。     

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.     

242例胆道手术患者胆汁成分与胆石成因研究

目的:研究胆道手术患者的胆汁成分与胆石形成的可能原因。方法:回顾性分析242例胆道手术病例的临床资料,统计分析其胆汁成分与其他生化检测数据。结果:1胆结石患病率女性显著高于男性;2年龄分布以40~60岁组最多;3病种以结石性慢性胆囊炎居首;4结石性质主要为胆固醇结石或胆固醇为主的混合结石;5胆固醇结石患者胆汁胆固醇、甘油三酯含量及腹壁脂肪厚度显著高于胆色素结石患者,组间比较具有统计学差异(P<0.05);6胆色素结石主要为胆道细菌感染后形成。结论:胆结石患者具有明显的性别、年龄等特征;胆固醇高易发胆固醇石,不易发生色素石,可能与胆固醇有易溶解胆色素的作用有关。     

养肝利胆颗粒对胆囊胆固醇结石豚鼠胰岛素抵抗的干预作用

目的：观察养肝利胆颗粒对胆囊胆固醇结石豚鼠胰岛素抵抗的调节作用。方法：选用80只豚鼠,雌雄各半,随机分成正常对照组、模型组、中药治疗组和西药治疗组共4组。用高脂高胆固醇饲养法建立胆囊胆固醇结石豚鼠模型。正常对照组和模型组灌服生理盐水,中药治疗组灌服养肝利胆颗粒,西药组灌服熊去氧胆酸。造模第49天每组各取8只进行高胰岛素-正葡萄糖钳夹实验,于实验期间测定葡萄糖输注率。实验结束处死豚鼠取材,观察胆结石成石率。结果：经胆结石红外光谱定性分析,豚鼠胆囊结石均为胆固醇结石。模型组成石率为83．25％。高胰岛素-正葡萄糖钳夹实验中模型组豚鼠葡萄糖输注率较正常对照组明显降低。与模型组相比,养肝利胆组与熊去氧胆酸组葡萄糖输注率明显升高,且养肝利胆组升高更为明显。结论：养肝利胆颗粒可以明显升高葡萄糖输注率,改善胆囊胆固醇结石豚鼠的胰岛素抵抗程度。     

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.     

EXPERIMENTAL STUDY OF PIGMENT GALLSTONE FORMATION AND DISSOLUTION

The bilirubin in the gall stones is identified chemically and by infrared spectroscopy and gel elec trophoresis as a polymer in structure. Its precipita- tion is closely related to the activity of B-glucuroni dase, yet it is not the sole factor in conjugated bili rubin hydrolysis resulting in bilirubin precipitation. The quantitative determination of hexoamine with modified Boas-Morgan method shows glycoprotein suggesting that the greater the amount of glycoprotein in the bile, the stronger the lithogenicity. Atomic emission and absorption spectroscopy analysis lead us to believe that any elements appearing in the plasma should also be foun.d in the bile or gallstone. The precipitation of solid substances in bile is strong Iy influenced by the alteration of Ca++ concentra tion, therefore the metal ions play an essential role in the formation of socalled insoluble components of the pigment gallstone. Dissolution tests reveal that increase of bile salt or glucuronic acid concen tration in bile can reduce bilirubin precipitation. Chelating agents deprive the metal ions of the stone, leading to breakage and partial dissolution of the stone. CDTA may be a promising drug for dissolu tion of pigment gallstones.