ABSTRACT
Objective To observe the dynamic changes of leptin and transforming growth factor (TGF)-β1 in formation of liver fibrosis in rats,and the role of leptin in liver fibrosis.Methods Six rats were served as normal control(0 week)and killed at the beginning of the study.Thirty-two rats were subcutaneously injected with 60%CCl4 to establish fibrotie models.The rats were than sacrificed at 3,6,9 and 12 weeks with eight each.Expressions of leptin mRNA,Ob-Rb mRNA,TGF-β1 mRNA and TGF-βRⅡmRNA in liver were detected by reverse-transcription polymerase chain reaction(RT-PCR).Expression of Smad3 and Smad7 proteins were determined by Western blot.The expression and loealization of leptin,Ob-Rb and TGF-β1 in liver tissue were detected by immunohistochemistry.Results The expression of leptin mRNA,Ob-Rb mRNA,TGF-β1 mRNA and TGF-βR Ⅱ mRNA in 0 week were 0.43±0.45,0.57±0.21,0.19±0.12 and 0.30±0.22,respectively,and increased to 1.27±0.19,1.70±0.29,1.70±1.00 and 2.14±1.02 at 12 weeks(P＜0.05).At the same times the level of Smad3 increased from 0.44±0.24 at 0 week to 1.75±1.05 at 12 weeks.While the expression of Smad7 was decreased from 1.35±0.12 at 0 week to 0.74±1.21 at 12 weeks(P＜0.05).The expressions of leptin,Ob-Rb and TGF-β1 were increased with the formation of the fibrosis(P＜0.01).Conclusions With the development of liver fibrosis,the expressions of leptin,Ob-Rb mRNA and protein are increased and improved the formation of the fibrosis.Its mechanisms may be correlated with up-regulation of TGF-β1,TGF-βR Ⅱ and Smda3 expressions and down-regulaton of Smad7 expression by leptin.