Dietary fenugreek and onion attenuate cholesterol gallstone formation in lithogenic diet-fed mice

An animal study was conducted to evaluate the antilithogenic effect of a combination of dietary fenugreek seeds and onion. Lithogenic conditions were induced in mice by feeding them a high (0.5%) cholesterol diet (HCD) for 10 weeks. Fenugreek (12%) and onion (2%) were included individually and in combination in this HCD. Fenugreek, onion and their combination reduced the incidence of cholesterol gallstones by 75%, 27% and 76%, respectively, with attendant reduction in total cholesterol content by 38-42%, 50-72% and 61-80% in serum, liver and bile respectively. Consequently, the cholesterol/phospholipid ratio was reduced significantly in serum, liver and bile. The cholesterol saturation index of bile was reduced from 4.14 to 1.38 by the combination of fenugreek and onion and to 2.33 by onion alone. The phospholipid and bile acid contents of the bile were also increased. Changes in the hepatic enzyme activities (3-hydroxy-3-methylglutaryl Coenzyme A reductase, cholesterol-7α-hydroxylase and cholesterol-27-hydroxylase) induced by HCD were countered by fenugreek, onion and their combination. Hepatic lipid peroxides were reduced by 19-22% and 39-45% with fenugreek, onion and their combination included in the diet along with the HCD. Increased accumulation of fat in the liver and inflammation of the gallbladder membrane produced by HCD were reduced by fenugreek, onion and their combination. The antilithogenic influence was highest with fenugreek alone, and the presence of onion along with it did not further increase this effect. There was also no additive effect of the two spices in the recovery of antioxidant molecules or in the antioxidant enzyme activities.     

炎症和凝血活化亢进在仓鼠胆囊胆固醇结石形成中作用的实验研究

目的：探讨胆囊炎症、胆汁凝血和纤溶与胆石形成之间的内在联系。 方法： 将仓鼠随机分为4组：正常组（喂养普通饲料6周），致石2周组（喂养致石饲料2周），致石6周组（喂养致石饲料6周），致石6周加阿司匹林组（喂养致石饲料和阿司匹林6周）。观察胆石形成情况、检测胆汁中D-二聚体（D-dimer）、C反应蛋白（CRP）、抗凝血酶Ⅲ抗原（AT-Ⅲ:Ag）含量、抗凝血酶Ⅲ活性（AT-Ⅲ:Ac）、凝血酶活性（F-Ⅱa:Ac）、纤溶酶活性（Plm:Ac）、纤溶酶原激活物抑制物活性（PAI:Ac）。 结果： 正常组、致石2周组、致石6周组和致石6周加阿司匹林组的胆石发病率分别为0%、20%、73%和25%。致石2周组和致石6周组胆汁的AT-Ⅲ:Ag、F-Ⅱa:Ac、D-dimer和CRP都明显高于正常组（P<0.01）；致石6周组的AT-Ⅲ:Ag、PAI:Ac、Plm:Ac、D-dimer和CRP明显高于致石2周组（P<0.01）。致石6周加阿司匹林组的D-dimer明显高于正常组（P<0.01）。致石6周加阿司匹林组的AT-Ⅲ:Ag、F-Ⅱa:Ac、PAI:Ac、D-dimer和CRP明显低于致石6周组（P<0.01）。CRP与D-dimer含量呈显著正相关（γ=0.752, P<0.01）。 结论： 胆石形成前即有凝血活化和交联纤维蛋白形成。“成石胆汁”通过刺激胆囊壁，引起胆囊壁炎症反应，从而使胆囊胆汁凝血活化，导致胆固醇结石的形成。     

Dietary effects of barley fibre, wheat bran and rye bran on bile composition and gallstone formation in hamsters.

The effects of brewer's spent grain (BSG), wheat bran and rye bran on bile composition, gallstone formation and serum cholesterol were studied in Syrian golden hamsters. The frequency of gallstone formation in the animals fed diets supplemented with low (10%) and high (20%) concentrations of BSG or wheat bran was significantly lower than that of the animals fed a stone-provoking, fibre-free diet. The ratios of secondary to primary bile acids were lower in the animals fed the diets supplemented with a high dose of BSG, wheat bran and rye bran than in the controls. The ratio of LCA to DCA was reduced only in the animals fed the diet supplemented with rye bran as compared with controls. No significant changes in bile and serum cholesterol levels were observed in the experiment.     

The influence of barley fibre on bile composition, gallstone formation, serum cholesterol and intestinal morphology in hamsters

Frequency of gallstones, concentration of bile acids and cholesterol in bile, concentration of cholesterol in serum, and structure of the small intestinal mucosa were analyzed in male Syrian Golden hamsters fed a stone provoking fibre-free diet with or without supplementation of brewer's spent grain (BSG), a concentrated barley fibre source from the by-product of brewing. A significantly lower frequency of gallstones was found in the animals with 10% BSG dietary supplementation. Addition of 30% BSG after an initial 6-week period with a fibre-free, stone provoking diet seemed to dissolve previously formed gallstones. Total bile acid concentration was higher in bile from animals given a diet supplemented with 10% BSG. In addition, the cholesterol concentration in both serum and bile was lower in the 30% BSG supplemented group. Structurally, a 10% BSG supplementation decreased ileal epithelium height whereas a high supplementation (30%) of BSG induced a decrease in epithelial height both of jejunal and ileal mucosa. The results show that BSG has significant effects on the metabolism of bile acids and cholesterol as well as on the morphology of the small intestinal mucosa.     

胆红素结石形成过程中氧自由基动态变化及与成石的关系

将兔随机分为胆道感染＋梗阻组、单纯胆道梗阻组及假手术组进行实验。结果发现：肝组织部分氧自由基与肝、胆汁的组织源性β－葡萄糖醛酸酶以及胆红素结石等的动态变化情况相似，它们之间呈显著正相关。同时，胆道感染＋梗阻组的上述指标均较单纯胆道梗阻组为高。提示：氧自由基可能通过脂质过氧化作用破坏溶酶体，致组织源性β－葡萄糖醛酸酶释放而参与结石的形成；单纯胆道梗阻可产生氧自由基经上述途径成石；加入大肠杆菌感染后可     

Rokitansky-Aschoff sinuses of the gallbladder are associated with black pigment gallstone formation: a scanning electron microscopy study

Rokitansky-Aschoff sinuses are the result of hyperplasia and herniation of epithelial cells through the fibromuscular layer of the gallbladder wall and are usually referred to as adenomyomatosis. The role of this study is to demonstrate that Rokitansky-Aschoff sinuses of the gallbladder are a risk factor for the formation of black pigment gallstones. A total of 179 removed gallbladders, were hystologically examinated. Sixty-four of the 179 consecutive cholecystomized patients had typical adenomyomatosis. Thirty-eight of the 64 patients with adenomyomatosis had black pigment gallstones, alone ( n =22) or in association with single ( n =12) or multiple ( n =4) cholesterol gallstones in the same gallbladder. Twelve of these patients did not have the typical risk factors for black stones (hemolysis, cirrhoses, gastrectomy, etc). Gallstones were examined by infrared spectroscopy and X-ray diffractometry. In addition, in a subset of 14 patients, the gallstones and the gallbladder wall were examined by scanning electron microscopy. At least in the initial phases of formation, Rokitansky-Aschoff sinuses were found close to small intraparietal vessels and sometimes they contained black pigment microstones. After the fourth to fifth decades of life, black gallstones can be found in the Rokitansky-Aschoff sinuses and in the main gallbladder lumen. Black pigment gallstones can form in Rokitansky-Aschoff sinuses of the gallbladder in absence of the typical risk factors for bilirubin suprasaturation of bile.     

高脂饲养致小鼠胰岛素抵抗对脂肪肝形成的影响

目的:探讨高脂饲养致小鼠脂肪肝形成的机制。方法:随机将8周雄性C57BL/6J小鼠分成高脂饲养组(给予含60%卡路里的高饱和脂肪酸饲养)和正常对照组,饲养12周。监测体重、肝重、血甘油三酯、血总胆固醇、血糖和血胰岛素水平,通过高胰岛素正葡萄糖钳夹实验反映胰岛素敏感性,HE染色、苏丹IV染色及肝脂含量反映肝组织脂质沉积情况,确定高脂饲养致小鼠脂肪肝的形成。通过Western blot法检测磷酸化胰岛素受体底物1(IRS1)和蛋白激酶B(Akt)水平反映胰岛素信号通路激活情况,检测固醇调节元件结合蛋白1(SREBP-1)和脂肪酸合成酶(FAS)蛋白水平反映肝内脂质合成的情况。结果:高脂饲养组小鼠体重及肝重较正常对照组小鼠明显增加。与正常对照组相比,高脂组血和肝组织内甘油三酯和总胆固醇含量显著升高,血清胰岛素水平升高,葡萄糖输注率减少,磷酸化IRS1和Akt水平降低。肝组织HE染色可见高脂组肝细胞胞浆内充满大量脂肪空泡,苏丹IV染色可见肝细胞内存在大量大小不一的红色脂滴;SREBP-1和FAS蛋白水平明显升高。给予外源性油酸干预原代正常肝细胞48 h,磷酸化IRS1和Akt水平呈浓度依赖性减低,而SREBP-1和FAS蛋白表达明显升高。结论:高脂饲养导致小鼠肝脏发生胰岛素抵抗,并通过激活SREBP-FAS脂肪合成途径,促进肝脏脂质沉积,从而诱发脂肪肝。     

Stimulation of peroxynitrite catalysis improves insulin sensitivity in high fat diet-fed mice

Peroxynitrite synthesis is increased in insulin resistant animals and humans. Peroxynitirite-induced nitration of insulin signalling proteins impairs insulin action in vitro , but the role of peroxynitrite in the pathogenesis of insulin resistance in vivo is not known. We therefore assessed the effects of a 1-week treatment with the peroxynitrite decomposition catalyst FeTPPS on insulin sensitivity in insulin resistant high fat diet-fed (HFD) and control mice. FeTPPS normalized the fasting plasma glucose and insulin levels ( P < 0.01), attenuated the hyperglycaemic response to an intraperitoneal glucose challenge by roughly 50% ( P < 0.05), and more than doubled the insulin-induced decrease in plasma glucose levels in HFD-fed mice ( P < 0.001). Moreover, FeTPPS restored insulin-stimulated Akt phosphorylation and insulin-stimulated glucose uptake in isolated skeletal muscle in vitro . Stimulation of peroxynitrite catalysis attenuates HFD-induced insulin resistance in mice by restoring insulin signalling and insulin-stimulated glucose uptake in skeletal muscle tissue.     

肝外胆道动力学因素在胆囊结石形成中的作用

目的：探讨肝外胆道动力学因素在胆囊结石形成中的作用。方法：选用家兔４７只随机分为４组。对照组（ｎ＝１３），成石组（ｎ＝１４），消炎痛组（ｎ＝１０），红霉素组（ｎ＝１０）。饲养４周后检测成石情况、胆总管压力等指标。结果：成石组１２／１４只形成结石，消炎痛组４／１０只形成结石，红霉素组无一只形成结石。成石组胆汁中胆固醇和粘蛋白含量显著增高，胆囊管阻力和胆总管压力显著增高，胆囊排空率显著降低。消炎痛组较成石组胆汁中粘蛋白浓度降低，胆囊管阻力下降，胆总管压力下降，胆囊排空率无显著改善。红霉素组较成石组胆汁粘蛋白含量下降，胆囊管阻力下降，胆囊排空率增加而胆总管压力无显著变化。结论：除胆汁成分异常外，肝外胆道动力学因素参与了胆囊结石形成，改变肝外胆道动力学因素以促进胆囊排空，能有效地防止胆囊结石形成     

Effect of cold stress on postnatal formation of mechanisms of carbohydrate hydrolysis and transport in the rat small intestine

Acute experiments using the accumulating mucosal preparation (AMP) method showed that cold adaptation (exposure for 2 h daily to a temperature of 6–7°C) of young rats during the first week after birth has a lasting inhibitory action on postnatal formation of the maltase transport and -amylase-transport digestion-assimilating systems but does not change the dynamics of development of the intrinsic transport systems. The same adaptation at the age of 10 to 17 days after birth, on the other hand, appreciably quickened the rates of formation of the hydrolytic-transport converyor on the outer surface of the cell membranes.Laboratory of Physiology of Digestion, Institute of Physiology, Academy of Sciences of the Uzbek SSR, Tashkent. (Presented by Academician V. N. Chernigovskii.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 88, No. 12, pp. 664–667, December, 1979.     

Effect of systemic BCG infection in syrian golden hamsters.

The response of Syrian golden hamsters to systemic infection with several doses of Mycobacterium bovis (strain BCG) was assessed. Large numbers of organisms (10(7)), injected intravenously, were lethal for hamsters, whereas all animals survived infection with 10(4) colony-forming units of BCG. Animals responded immunologically to purified protein derivative as assessed by increased footpad swelling and splenic lymphocyte proliferation. The immediate cause of death was a diffuse granulomatous interstitial pneumonia.