瘦素调节胆汁酸代谢影响胆石形成

›› 2019, Vol. 39 ›› Issue (12): 1723-1728.

瘦素调节胆汁酸代谢影响胆石形成

何静宇¹,温剑²,杨闯¹,张永川¹

1. 绵阳市第三人民医院
2. 西南医科大学附属医院肝胆胰外科

收稿日期:2019-03-29 修回日期:2019-09-22 出版日期:2019-12-05 发布日期:2019-12-04
通讯作者: 杨闯 E-mail:ycdoctor@sina.com
基金资助:
四川省卫生和计划生育委员会科研课题

Leptin influences cholelithiasis formation by regulating bile acid metabolism

Received:2019-03-29 Revised:2019-09-22 Online:2019-12-05 Published:2019-12-04

摘要/Abstract

摘要： 目的探讨瘦素（leptin）和胆汁酸代谢之间的关系及其对胆石症的影响。方法：收集手术治疗的89例胆囊结石患者（GS），68例原发性肝内胆管结石患者（PIS）和72例肝脏良性疾病患者（CT）的肝脏组织及术前血清。放射免疫法测定血清瘦素水平，自动生化分析检测血清中TBA、TBIL、ALT、AST、TC、TG和γ-GGT水平。Q-PCR和Western blot分别检测肝脏组织长型瘦素受体（OB-Rb）、腺苷酸活化蛋白激酶-a2(AMPK-a2)、p-AMPKa2、胆盐输出泵（BSEP）的mRNA及蛋白表达量。HepG2细胞分别与瘦素和瘦素＋AMPKa2抑制剂（compund C）共培养后，Q-PCR和Western blot分别检测细胞OB-Rb、AMPKa2、p-AMPKa2、BSEP的mRNA和蛋白表达量，自动生化分析仪检测HepG2细胞培养上清液中TBA含量。结果：GS组血清瘦素水平明显高于CT和PIS组（P＜0.05）。GS组和PIS组的OB-Rb、AMPKa2、p-AMPKa2 和BSEP表达水平显著低于CT组（P＜0.05）。瘦素刺激HepG2细胞后增加其OB-Rb、AMPKa2、p-AMPKa2 和BSEP表达量。Compund C抑制瘦素对HepG2细胞中OB-Rb、AMPKa2、p-AMPKa2 和BSEP的促表达作用。结论：瘦素参与胆汁酸代谢的调节，其在肝脏的代谢异常可能是胆石症发生的机制之一。

关键词: 瘦素，胆汁酸，胆盐输出泵，胆石症

Abstract: Objective To further investigate the relationship between leptin and bile acid metabolism. Methods Liver tissues and preoperative serum of 89 patients with Gall Stone (GS), 68 patients with Primary intrahepatic Stone (PIS) and 72 patients with benign liver diseases (Control, CT) were collected. Serum leptin levels were measured by radioimmunoassay, and the serum TBA, TBIL, ALT, AST, TC, TG and gamma-ggt levels were detected by automatic biochemical analysis. mRNA and protein expression levels of Adenosine monophosphate-activated protein kinase-a2, p-AMPKa2 and bile salt export pump (BSEP) in liver samples were measured by Q-PCR and Western blot, respectively. After co-culture of HepG2 cells with leptin and leptin+AMPKa2 inhibitor (compund C), mRNA and protein expressions of OB-Rb, AMPKa2, p-AMPKa2 and BSEP were detected by Q-PCR and Western blot, respectively. TBA content in cell supernatant was detected by automatic biochemical analysis. Results serum leptin level in GS group was significantly higher than that in CT and PIS group (P < 0.05). The expression levels of OB-Rb, AMPKa2, p-AMPKa2 and BSEP in GS group and PIS group were significantly lower than those in CT group (P < 0.05). Leptin stimulates HepG2 cells and increases the expressions of OB-Rb, AMPKa2, p-AMPKa2 and BSEP. Compund C inhibits the effect of leptin on OB-Rb, AMPKa2, p-AMPKa2 and BSEP in HepG2 cells. Conclusions Leptin is involved in the regulation of bile acid metabolism, and its abnormal effect in liver may be one of the mechanisms of cholelithiasis.

Key words: Leptin, Bile acid, BSEP, Cholelithiasis

中图分类号:

何静宇温剑杨闯张永川. 瘦素调节胆汁酸代谢影响胆石形成[J]. , 2019, 39(12): 1723-1728.

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