BACKGROUND The cholesterol gallstones diseases (CGD) is highly correlated with metabolic syndrome and type 2 diabetes. The present study aimed to investigate preventive effects of pioglitazone (PIO), an antidiabetic drug, on the CGD in guinea pigs fed with a lithogenic diet (LD). METHODS The guinea pigs were fed with the LD for 8 weeks. All guinea pigs were grouped as follows: low fat diet; LD; LD plus PIO (4 mg/kg); LD plus PIO (8 mg/kg); LD plus ezetimibe (EZE) (2 mg/kg). Gallbladder stones were observed using microscopy. The profile of biliary composition, and blood glucose, insulin and lipid were analyzed. The liver or ileum was harvested for determinations of hydroxyl-methyl-glutaryl-CoA reductase (HMGCR), sterol regulatory element-binding proteins 2 (SREBP2), 7α-hydroxylase (CYP7A1), adenosine triphosphate-binding cassette (ABC) sterol transporters G5 and G8 (ABCG5, ABCG8), bile salt export pump (BSEP), Niemann-Pick C1-Like 1 (NPC1L1) and acetyl-coenzyme A cholesterol acyltransferase (ACAT2) by Western blot. The gallbladders were used for histological examination. RESULTS The LD successfully induced gallstone. Both pioglitazone and ezetimibe prevented gallstone formation, as well as hepatic and cholecystic damages. Pioglitazone significantly decreased HMGCR and SREBP2, but increased CYP7A1, ABCG5, ABCG8, and BSEP in the liver. Pioglitazone also remarkably decreased NPC1L1 and ACAT2, while increased ABCG5/8 in the intestine. The beneficial alterations of cholesterol and bile acids in the bile, as well as profile of glucose, insulin and lipid in the blood were found in the guinea pigs treated with pioglitazone. CONCLUSION Pioglitazone has a noticeable benefit towards the CGD, which is involved in changes of synthesis, transformation, absorption, and transportation of cholesterol.

中文翻译：

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吡格列酮通过调节成石饮食的豚鼠体内的胆固醇稳态来防止胆固醇胆结石的形成。

背景技术胆固醇结石病（CGD）与代谢综合征和2型糖尿病高度相关。本研究旨在研究吡格列酮（PIO）（一种抗糖尿病药物）对以石原饮食（LD）喂养的豚鼠中CGD的预防作用。方法给豚鼠喂LD，持续8周。所有豚鼠的分组如下：低脂饮食；低脂饮食；低脂饮食；低脂饮食；低脂饮食。LD; LD加PIO（4 mg / kg）；LD加PIO（8 mg / kg）；LD加依折麦布（EZE）（2 mg / kg）。使用显微镜观察胆囊结石。分析胆汁成分，血糖，胰岛素和脂质。收集肝脏或回肠用于测定羟甲基-甲基-戊二酰-CoA还原酶（HMGCR），固醇调节元件结合蛋白2（SREBP2），7α-羟化酶（CYP7A1），蛋白质印迹法检测三磷酸腺苷结合盒（ABC）固醇转运蛋白G5和G8（ABCG5，ABCG8），胆盐输出泵（BSEP），Niemann-Pick C1-Like 1（NPC1L1）和乙酰辅酶A胆固醇酰基转移酶（ACAT2） 。胆囊用于组织学检查。结果LD成功诱发了胆结石。吡格列酮和依折麦布均可以预防胆结石的形成以及肝和胆囊的损害。吡格列酮显着降低HMGCR和SREBP2，但增加肝脏中的CYP7A1，ABCG5，ABCG8和BSEP。吡格列酮还显着降低了NPC1L1和ACAT2，同时增加了肠道中的ABCG5 / 8。在用吡格列酮治疗的豚鼠中发现胆汁中胆固醇和胆汁酸的有益变化以及血液中葡萄糖，胰岛素和脂质的分布。