葛根素治疗2型糖尿病KKA^y小鼠肝脏损伤的实验研究  

Effect of Puerarin on Liver Injury in KKAy Mice with Type 2 Diabetes Mellitus

作　　者：杨硕[1] 娄金丽[1] 王谦[2] 郑宏[3] 黄启福[2] 

机构地区：[1]首都医科大学附属北京佑安医院,北京100069 [2]北京中医药大学基础医学院 [3]北京中医药大学东方医院

出　　处：《中国中西医结合杂志》2009年第8期707-710,共4页Chinese Journal of Integrated Traditional and Western Medicine

基　　金：国家自然科学基金资助项目(No.30572437);博士后基金资助项目(No.2006037321)

摘　　要：目的研究2型糖尿病(T2DM)肝脏损伤的发生及可能的发病机制,探讨葛根素注射液的干预作用。方法选取T2DM小鼠(KKAy)随机分为模型组和葛根素组。同龄C57BL/J小鼠作为正常对照组。28周龄后处死小鼠,全自动生化法检测空腹血糖(FBG)、甘油三酯(TG)、胆固醇(TC)、谷丙转氨酶(ALT)、谷草转氨酶(AST)等生化指标;流式细胞仪检测肝细胞凋亡情况;电镜观察肝组织病理形态学改变;RT-PCR法检测凋亡相关基因bcl-2、baxmRNA的表达;紫外分光光度检测肝组织超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)活力、丙二醛(MDA)含量及Na+-K+-ATP酶活性。结果与正常对照组比较,模型组KKAy小鼠血清FBG、TG、TC、ALT、AST含量均增高(P<0.01);肝脏凋亡细胞百分率增高(P<0.01);可见肝脏线粒体肿胀、损伤;bcl-2表达下调,bax表达上调(P<0.01);肝组织中SOD,GSH-Px,Na+-K+-ATP酶活性降低,MDA含量增高(P<0.01)。葛根素组治疗后,小鼠以上各项指标均有所改善。结论糖尿病KKAy小鼠存在明显肝损害;葛根素可通过上调bcl-2,从而抑制氧化应激,改善小鼠肝脏能量代谢障碍,对糖尿病引起的氧化损伤有保护作用。Objective To study the possible pathogenic mechanism of liver injury in type 2 diabetes mellitus （T2DM） and the intervening effect of puerarin on it. Methods Mice with T2DM （KKA^y） were randomly divided into two groups, the model group and the puerarin group. And the C57BL/J mice of the same age were set up as normal controls. They were sacrificed at 28 weeks old for observing serum fasting blood glucose （ FBG）, triglyceride （ TG）, total cholesterol （TC）, alanine aminotransferase （ ALT）, aspartate aminotransferase （AST） by automatic biochemistry; liver cell apoptosis by flow cytometry; pathomorphology by electron microscope; and mRNA expressions of bcl-2 and bax genes by RT-PCR; as well as the activities of superoxide dismutase （ SOD）, glutathione peroxidase （ GSH-Px）, Na ^＋-K^ ＋ -ATPase ; and content of malondialdehyde （MDA） in liver tissue by spectrophotometer. Results In KKA^y mice, blood levels of FBG, TG, TC, ALT, AST and liver cell apoptosis rate were higher; the bax mRNA expression was higher and bcl-2 mRNA was lower markedly; the activities of SOD, GSH-Px,Na^＋-K^＋-ATPase in liver tissue were lower, and MDA content was higher than those in the normal control significantly （ all P 〈 0.01 ）. Besides, mitochondria Swelling and damage were found in liver tissue. While in the puerarin group after treatment, all the above-mentioned changes were alleviated to some extent. Conclusions Obvious liver injury emerges in KKA^y mice. Puerarirl shows a protective effect on the T2DM caused oxidative damage by way of up-regulating bcl-2 to inhibit oxidative stress, and improving the energy metabolic dysfunction in liver of mice.

关 键 词：2型糖尿病 肝损害 氧化应激 BCL-2/BAX 葛根素 

分 类 号：R285.5[医药卫生—中药学]