瘦素及转化生长因子-β1与四氯化碳诱导大鼠肝纤维化模型逆转恢复的相关性研究  

Correlative research between leptin and TGF-β1 and the recovery on CCl_4 induced hepatic fibrosis in rats

作　　者：李浩[1] 李俊[1] 黄成[1] 黄艳[1] 张磊[1] 李政通[1] 章圣朋[1] 程娟[1] 

机构地区：[1]安徽医科大学药学院,安徽合肥230032

出　　处：《中国药理学通报》2011年第4期473-477,共5页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No81072686;30873081);教育部博士学科点新教师基金项目(No20103420120001)

摘　　要：目的研究瘦素(Leptin)及转化生长因子-β1(TGF-β1)与四氯化碳(CCl4)诱导大鼠肝纤维化逆转恢复的相关性。方法采用CCl4大鼠肝纤维化模型,分别于逆转恢复0、2、4、6、8周处死大鼠,取血清检测谷丙转氨酶(ALT)、谷草转氨酶(AST)、透明质酸(HA)、Ⅳ型胶原(CⅣ)、Leptin和TGF-β1含量;取肝组织进行Masson染色,羟脯氨酸(Hyp)含量检测,逆转录聚合酶链反应(RT-PCR)检测Leptin、TGF-β1、瘦素功能型受体(OB-Rb)和转化生长因子-β1型受体(TGF-βRⅠ)mRNA表达,Western blot法检测核转录因子-κb(NF-κb)蛋白表达。结果 CCl4致大鼠肝纤维化在停止注射后发生逆转恢复;血清ALT、AST、HA、CⅣ、Leptin和TGF-β1含量以及肝组织Hyp含量在逆转恢复过程中逐渐降低;同时肝组织Leptin、TGF-β1、OB-Rb和TGF-βRⅠmRNA以及NF-κb蛋白表达亦出现不同程度下降;血清Leptin及TGF-β1水平与HA、CⅣ、Hyp变化呈正相关(P<0.01)。结论 CCl4致大鼠肝纤维化的逆转恢复与Leptin及TGF-β1下降关系密切;可能通过受体表达下调降低促纤维化因子作用,进而影响肝纤维化逆转恢复过程。Aim To study the correlation between leptin,transforming growth factor-β1（TGF-β1）and the recovery on CCl4 induced hepatic fibrosis in rats.Methods Hepatic fibrosis was induced by CCl4 in rats.After stopping CCl4 injection,rats were sacrificed on week 0,2,4,6,8.The serum was taken for ALT,AST,HA,CⅣ,leptin and TGF-β1 measuring.Liver tissues were taken for pathological examination and hydroxyproline detection.Leptin,TGF-β1,OB-Rb and TGF-βRⅠmRNA were examined by RT-PCR,while NF-κb protein was measured by Western blot.Results After stopping CCl4 injection,the hepatic fibrosis in rats could recover.The levels of ALT,AST,HA,CⅣ,leptin and TGF-β1 in serum significantly declined.The degrees of mRNA expression of leptin,TGF-β1,OB-Rb and TGF-βRⅠand protein expression of nuclear factor kappa-b（NF-κb）were decreased.In addition,leptin and TGF-β1 significantly correlated with the recovery on CCl4 induced hepatic fibrosis in rats.Conclusions During the recovery on CCl4 induced hepatic fibrosis,leptin and TGF-β1 play an important role.They might affect the recovery through down-regulating the receptors and decreasing the promotion factors.

关 键 词：瘦素 瘦素受体 肝纤维化 转化生长因子-Β1 肝星状细胞 核转录因子-ΚB 

分 类 号：R-332[医药卫生] R322.47