过氧化物酶体增殖物激活受体γ配体抑制大鼠肝纤维化的实验研究

Peroxisome proliferator activated receptor gamma ligand suppresses hepatic fibrosis in rats

目的研究过氧化物酶体增殖物激活受体γ（peroxisome prolifcrator activated receptorgamma，PPARγ）配体对大鼠肝纤维化的作用。方法将Wistar大鼠40只随机分为两组，对照组（20只）和罗格列酮组（20只）。所有动物使用饮水中加入质量比0．3‰硫代乙酰胺的方法制作肝纤维化模型。对照组喂饲普通颗粒饲料。罗格列酮组喂饲含200ppm罗格列酮的颗粒饲料。喂饲6个月后，用RT—PCR方法检测肝纤维化大鼠肝脏PPARγ、TGF—β1及Ⅰ型前胶原mRNA表达，用Western blot法检测PPARγ、TGF—β1、Ⅰ型胶原及α平滑肌肌动蛋白（α-SMA）表达，用Van Gieson（VG）染色的方法检测肝组织切片的胶原表达情况。结果罗格列酮组与对照组相比，PPARγmRNA表达显著增强（t=6．93，P〈0．01），TGF—β1，mRNA（t=3．89，P〈0．01）和Ⅰ型前胶原mRNA表达显著降低（t=5．67，P〈0．01）。PPARγ、TGF—β1，及Ⅰ型胶原蛋白表达所得结果与RT—PCR结果相一致。罗格列酮组与对照组相比，α-SMA表达显著降低（t=3．12，P〈0．01）。罗格列酮组肝组织切片的胶原染色低于对照组（t=3．47，P〈0．01）。结论PPARγ配体能够抑制大鼠纤维化肝脏的胶原产生，在体内具有一定的抗肝纤维化作用。

Objective To study the effect of peroxisome proliferator-activated receptor gamma （PPARγ） ligand on hepatic fibrosis in rats. Methods Forty Wistar rats were randomly divided into two groups： the control group（20 rats） ,in which liver cirrhosis was induced by adding 0. 3‰ thioacetamide in the fodder for 6 months, and rosiglitazone group （20 rats） in which 200 ppm of rosiglitazone in combination with 0. 3‰ thioacetamide was added in the fodder. Liver tissue＇s mRNA expression of PPARγ, TGF-β1, type Ⅰ pro-collagen and α-smooth muscle actin（α-SMA） was detected by RT-PCR. The protein expression of PPARγ, TGF-β1 ,type Ⅰ collagen and α-SMA was detected by Western blot. The expression of collagen of liver histological section was evaluated by Van Gieson （VG） staining. Results The expression of PPARγ, at mRNA level significantly increased in rosiglitazone group compared with those in the control group （ t = 6.93, P 〈 0. 01 ）, while the expression of TGF-β1 （ t = 3.89, P 〈 0.01 ） and type Ⅰ pro-collagen （ t = 5.67 ,P 〈0.01 ） were lower than that in the control group. The protein expression of PPARγ, TGF-β1 and type Ⅰ collagen was in similar tendence with that of mRNA expression. The expression of α-SMA decreased significantly in rosiglitazone group compared with that in the control group （ t = 3.12, P 〈 0. 01 ）. The collagen stainings of liver histological section in rosiglitazone group was lower than those in the control group （ t = 3.47, P 〈 0. 01 ）. Conclusion PPARγ ligand inhibits the production of collagen in fibrotic livers in rats and prevents hepatic fibrosis in vivo.