浙江医学2017，Vol.39Issue(9)：688-693,后插2,7.DOI:10.12056/j.issn.1006-2785.2017.39.9.2017-326
棉酚对T2DM合并NAFLD大鼠肝脏的保护作用
Heptoprotective effect of gossypol in type 2 diabetic rats complicated with non-alcoholic fatty liver disease
摘要
Abstract
Objective To investigate the hepatoprotective effect of gossypol in type 2 diabetic (T2DM) rats complicated with non-alcoholic fatty liver disease (NAFLD).Methods Thirty male Sprague-Dauley rats were divided randomly into normal control group,T2DM group and gossypol-treated group with 10 in each group.After being fed with high-fat feeding for 4 weeks,the latter two groups were injected with strepozotocin (30mg/kg) intraperitoneally to induce T2DM.The rats in gossypol treated group were given gossypol at a dose of 15mg·kg-1·d-1 for 4 weeks by gavage,then at a dose of 15mg ·kg-1·d-1 until the end of week 12.At the end of the experiment all animals were sacrificed,the concentration of serum ALT,AST,ALB and HA were measured.The ultrastructural changes of liver were observed by transmission electron microscopy(TEM),the pathologic changes and fibrosis of liver were observed by light microscopy (LM) with HE staining and Masson staining respectively.Additionally,the activated hepatic stellate cells (HSCs) and the protein expression of 11 beta-hydroxysteroid dehydrogenase type 1 (1 1β-HSD1) and glucocorticoid receptors (GR) was assayed by immunohistochemistry (IHC),the mRNA expression of phosphoenolpyruvate carboxykinase (PEPCK),glucose-6-phosphatase (G6Pase),insulin receptor and leptin receptor in liver tissue was assayed by semi-quantitative RT-PCR.Results The levels of serum ALT,AST,HA increased(P＜0.05),serum ALB decreased(P＜0.05),the 11 β-HSD1 and GR protein expression increased (P＜0.05),the mRNA expression of insulin receptor,leptin receptor increased (P＜0.05) in liver tissue of T2DM group compared with normal control group.Clinical pathology showed obvious liver hydropic degeneration,fatty degeneration,ballooning degeneration,inflammatory infiltration,fibrosis,a great number of activated HSCs in liver tissue of T2DM group.The levels of serum ALT,AST,HA decreased (P＜0.05),serum ALB increased (P＜0.01),the 11 β-HSD1 and GR protein expression decreased (P＜0.05),the mRNA expression of PEPCK,G6Pase,insulin receptor and leptin receptor decreased (P＜0.05) in liver tissue of gossypol treated group compared with diabetic group.The hydropic degeneration,fatty degeneration,ballooning degeneration,inflammatory infiltration in liver tissue were improved slightly but the hepatic fibrosis was attenuated and the number of activated HSCs was reduced in gossypol treated group significantly compared with T2DM group.Conclusion Low dosage gossypol can attenuate fibrosis of NAFLD in diabetic rats.Down regulation of mRNA expression of 11 β-HSD1,insulin receptor and leptin receptor may be involved in it.关键词
棉酚/2型糖尿病/非酒精性脂肪性肝病/Ⅰ型11β类固醇脱氢酶/瘦素受体/胰岛素受体Key words
Gossypol/Type 2 diabetes/Nonalcoholic fatty liver disease/11beta-hydroxysteroid dehydrogenase type 1/Leptin receptor/Insulin receptor引用本文复制引用
王家员,樊建霜,吴亮,黄卡特,王蓉蓉..棉酚对T2DM合并NAFLD大鼠肝脏的保护作用[J].浙江医学,2017,39(9):688-693,后插2,7.基金项目
温州市科技计划项目(Y20120010) （Y20120010）
