摘要
目的:研究实验性非酒精性脂肪性肝炎(NASH)大鼠转化生长因子-β1(TGF-β1)、基质金属蛋白酶-2(MMP2)、基质金属蛋白酶抑制因子-2(TIMP2)表达情况及氨基胍(AG)的干预作用。方法:SD大鼠28只,随机分为3组,模型组(M组)、氨基胍组(A组)、正常组(N组)。检测各组大鼠肝湿重、血糖(GLU)、谷丙转氨酶(ALT)、三酰甘油(TG)、胆固醇(CHO)及透明质酸(HA)含量。免疫组化法判断各组大鼠肝脏病理学变化。竞争性ELISA测定血清糖基化终产物(AGEs)及TGF-β1含量。Western-blot检测肝组织TGF-β1及MMP2、TIMP2蛋白表达情况。结果:M组大鼠肝湿重和血清GLU、ALT、TG、CHO水平比N组升高。A组较N组轻度增高,与M组无明显差异。M组及A组肝脏炎症活动度及纤维化半定量计分较N组升高,而A组较M组降低。M组大鼠血清AGEs、HA、TGF-β1含量较N组升高。而A组较M组降低。肝组织TGF-β1蛋白表达与各组血清检测结果平行,而MMP2/TIMP2值则相反。结论:NASH大鼠血清及肝组织中TGF-β1上调,MMP2/TIMP2值下降,AG可抑制TGF-β1、上调MMP2/TIMP2值,减缓NASH大鼠肝损伤进程。
OBJECTIVE To study the levels of TGF-β1, MMP-2 and TIMP-2 in rats with non-alcoholic steatohepatitis and the effects of aminoguanidine （AG） on it. METHODS Nowalcoholic steatohepatitis was induced by a diet rich in fat. Twenty eight male Spraque-Dawly（SD） rats were randomly divided into three groups： model group （group M）, aminoguanidine treatd group （group A） and normal control group （group N）. The wet weight of rat liver and the levels of GLU, ALT, TG, CHO and HA in serum in different groups were examined. Immuno-histochemistry was performed to assess the histopathologic chan ges. Competitive ELISA was used to detect AGEs and TGF-β. Western-blot was performed to detect the protein expression of TGF-βl, MMP-2 and TIMP 2. RESULTS Compared with group N, the wet weight of rat liver and the levels of GLU,ALT, TG, CHO and HA in group M were increased, no significant difference between group M and A. The degree of liver inflamma tion and fibrosis semiquantative scoring in group M and A was higher than group N, and the degree in group A was lower than group M. Levels of serum AGEs,HA,TGF- β1 by Competitive ELISA and the protein of TGF-β1 in liver tissues by Western blot were paralleled with the above findings, but the ratio of MMP2 and TIMP2 was just the reverse. CONCLUSION The ex pression of TGF-β1 increased and the ratio of MMP2 and TIMP2 decreased with the development of rat non-alcoholic steatohep atitis. AG retards the process of liver injury by depressed the expression of TGF-β1 and up regulation of the ratio of MMP2 and TIMP2.
出处
《中国医院药学杂志》
CAS
CSCD
北大核心
2014年第5期355-359,共5页
Chinese Journal of Hospital Pharmacy
基金
福建省厦门市科技计划资助项目(编号:3502Z20074006)
