苓桂术甘汤对NASH大鼠肝组织DGAT2、PKCε的作用研究

毛堂友; 韩海啸; 赵唯含; 王允亮; 高康丽; 陈晓伟; 李军祥

doi:10.3969/j.issn.1671-038X.2016.02.02

苓桂术甘汤对NASH大鼠肝组织DGAT2、PKCε的作用研究

- 1. 北京中医药大学, 北京 100029;
- 2. 北京中医药大学东方医院脾胃肝胆科, 北京 100078
基金项目:
高等学校博士学科点专项科研基金（No：20130013110007）

详细信息

作者简介:
毛堂友,博士研究生,专业:中医内科学

通讯作者: 李军祥,E-mail:lijunxiang1226@163.com

中图分类号: R575.1

收稿日期: 2015-08-08

Experimental study of Linggui Zhugan Decoction on DGAT2 and PKCε expression in NASH rats

- 1. Beijing University of Chinese Medicine, Beijing 100029, China;
- 2. Department of Gastroenterology, Dongfang Hospital of Beijing University of Chinese Medicine, Beijing 100078, China

More Information

Corresponding author: LI Jun-xiang, E-mail: lijunxiang1226@163.com

Received Date: 08 August 2015

摘要

摘要: [目的]探讨苓桂术甘汤对非酒精性脂肪性肝炎（NASH）大鼠肝组织DGAT2、PKCε的影响。[方法]高脂饮食饲养SD大鼠8周制备NASH模型，药物治疗4周后，自动生化分析仪检测血清肝功能（AST、ALT）、血脂（CHO、LDL、HDL、TG）水平，苏木精-伊红染色、油红O染色观察肝组织病理，RT-PCR检测DGAT2 mRNA、PKCε mRNA，Western-blot检测DGAT2和PKCε蛋白的表达。[结果]苓桂术甘汤组、罗格列酮组能明显改善肝组织的脂肪变性和炎症程度，降低血清TG、ALT、AST，下调DGAT2、PKCε mRNA和蛋白的表达水平（P<0.05、P<0.01）。[结论]苓桂术甘汤可能是通过下调肝组织DGAT2、PKCε mRNA和蛋白的表达水平，[JP2]对肝内脂质代谢和胰岛素抵抗起到了调节和改善作用，从而达到治疗NASH的目的，DGAT2/PKCε有可能成为治疗NASH的新靶点。
- 苓桂术甘汤 /
- 非酒精性脂肪性肝炎 /
- DGAT2 /
- PKCε
Abstract: [Objective] To investigate the effect of Linggui Zhugan Decoction on DGAT2 and PKCε expression in NASH rats.[Methods] High-fat diet was used to induce NASH model on SD rats for 8 weeks.After 4 weeks of treatment, the automatic biochemical analyzer was used to measure the serum liver function(AST, ALT) and blood lipid(CHO, LDL, HDL, TG) level.HE staining and oil-red O staining were used to observe the pathological changes of liver tissue.RT-PCR was used to detect the DGAT2 mRNA and PKCε mRNA.Western blot was used to observe the expression of DAGT2 and PKCε protein.[Results] Linggui Zhugan Decoction and rosiglitazone can significantly improve the liver fatty degeneration and the degree of inflammation, reduce serum TG, ALT, AST, downregulate DGAT2, PKCε mRNA and protein expression levels(P<0.05, P<0.01).[Conclusion] Linggui Zhugan Decoction may treat NASH through downregulation of hepatic DGAT2, PKCε mRNA and protein expression levels, thus adjusting the intrahepatic lipid metabolism and improving insulin resistance.DGAT2/PKCε may become a new target for the treatment of NASH.
- Linggui Zhugan Decoction /
- NASH /
- DGAT2 /
- PKCε

HTML全文

参考文献(9)

[1]	ANGULO P.Nonalcoholic fatty liver disease[J].N Engl J Med, 2002, 346:1221-1231.
[2]	BRUNT E M.Nonalcoholic steatohepatitis[J].Semin Liver Dis, 2004, 24:3-20.
[3]	刘莹.茵陈蒿汤及其拆方治疗非酒精性脂肪性肝炎的实验研究[D].北京:北京中医药大学, 2013.
[4]	CHEN H C, SMITH S J, LADHA Z, et al.Increased insulin and leptin sensitivity in mice lacking acyl CoA:diacylglycerol acyltransferase 2[J].J Clin Invest, 2002, 109:1049-1055.
[5]	JORNAYVAZ F R, BIRKENFELD A L, JURCZAK M J, et al.Hepatic insulin resistance in mice with hepatic overexpression of diacylglycerol acyltransferase 2[J].Proc Natl Acad Sci USA, 2011, 108:5748-5752.
[6]	MONETTI M, LEVIN M C, WATT M J, et al.Dissociation of hepatic steatosis and insulin resistance in mice overexpressing DAGT in the liver[J].Cell Metab, 2007, 6:69-78.
[7]	SAMUEL V T, LIU Z X, WANG A, et al.Inhibition of protein kinase C epsilon prevents hepatic ins ulin resistance in nonalcoholic fatty liver disease[J].J Clin Invest, 2007, 117:739-745.
[8]	KUMASHIRO N, ERION D M, ZHANG D, et al.Cellular mechanism of insulin resistance in nonalcoholic fatty liver disease[J].PNAS, 2011, 108:16381-16385.
[9]	柳涛, 杨丽丽, 张莉, 等.不同治法复方防治非酒精性单纯性脂肪肝的效应差异[J].中西医结合学报, 2012, 10(10):1120-1126.