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杨硕,娄金丽,王谦,郑宏,黄启福.葛根素治疗2型糖尿病KKA~y小鼠肝脏损伤的实验研究[J].,2009,(8):707-710
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
  
DOI:
中文关键词:  2型糖尿病  肝损害  氧化应激  bcl-2/bax  葛根素
英文关键词:type 2 diabetes mellitus  liver injury  oxidative stress  bcl-2/bax  puerarin
基金项目: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)
Author NameAffiliation
YANG Shuo 首都医科大学附属北京佑安医院 
LOU Jin-li 首都医科大学附属北京佑安医院 
WANG Qian 北京中医药大学基础医学院 
郑宏 北京中医药大学东方医院 
黄启福 北京中医药大学基础医学院 
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中文摘要:
      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。
英文摘要:
      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 (KKAy) 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 KKAy 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 KKAy mice. Puerarin 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.
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