| Objective:To study the expression and signification of peroxisome proliferator activated receptorγ(PPARγ)and its intervention by rosiglitazone in immuno-hepatic fibrosis rats,and to clarify the relationship between PPARγand hepatic fibrogenesis.Methods:The rats were randomly divided into the following groups:normal controls,hepaticfibrosismodels,ratstreated with rosiglitazone,starting at the fifth week since the rats exposed to porcome serum.ALL rats were sacrificed and their liver were collected for further determinations at the corresponding week.The liver histopathology was examined by HE and VG staining.The expressions and sites of PPARγ,and transforming growth factorβ1(TGF-β1)α-SMA in liver tissue were also detected by immunohistochemical staining,the expressions and sites of PPARγin liver tissue was detected by hybridization in situ staining,and the quantitative analysis of the positive expression was carried out through the imagine analysis system.Results:The immuno-hepatic fibrosis was induced in rats by porcine serum successfully.At the fourth week,the proliferation of fibous tissue in the liver wasn't manifest and there is no significance compared with the normal controls(0.0126±0.00443VS0.0055±0.00331,P＞0.05). The collagen in the liver proliferates both at the sixth week and at the eighth week,the percentage of the area of collage was significantly increased compared with the normal controls (0.0183±0.00810VS0.0246±0.00935VS0.0055±0.00331,P＜0.01).With the development of liver fibrosis,the expressions of PPARγ,and PPARγ-mRNA in liver tissue were decreased gradually at the sixth and eighth week(immunohistochemistry 7.2289±2.99494 VS 2.7312±0.98173 VS1.5831±0.96014,P＜0.05;in-situ hybridization 12.4668±3.72355 VS 8.9313±1.04991VS 7.9767±2.93757,P＜0.05);the expression ofα-SMA in liver tissue were increased gradually at the sixth and eighth week(2.6386±1.24404 VS 5.7625±1.98481 VS 7.6469±2.17917,P＜0.05),the expression of TGF-β1 in liver tissue were significantly increased(0.1787±0.02350 VS0.2294±0.01380VS0.2493±0.03331VS0.2871±0.03310,P＜0.01).At the sixth and eighth week,the expression of PPARγand PPARγ-mRNA in liver ti- ssue was increased in rats treated with rosiglitazone compared with the corresponding model rats(immuneohistochemistry 5.4456±0.61748 VS 2.7312±0.98173,P＜0.05,3.8198±0.46354 VS 1.5831±0.96014,P＜0.05;in-situ hybridization 10.5337±2.07476 VS 8.9313±1.04991,P＜0.05, 11.2218±1.86563VS7.9769±2.93757,P＜0.05),the expression ofα-SMA in liver tissue was decreased in rats treated with rosiglitazone compared with the corresponding model rats (3.1829±1.02028 VS5.7625±1.98481,P＜0.05,5.5236±0.38050 VS7.6469±2.17917P＜0.05), but the percentage of the area of collage and the expression of TGF-β1 in liver tissue was not decreased significantly at the sixth week(0.0113±0.00604VS0.0183±0.00810,P＞0.05; 0.2399±0.028804VS0.2493±0.03331,P＞0.05),at the eighth week,the percentage of the area of collage and the expression of TGF-β1 in liver tissue were decreased compared with the corresponding model rats(0.01144±0.00563 VS0.0246±0.00935,P＜0.01;0.1925±0.03655 VS 0.2871±0.03310,P＜0.001).The expression of PPARγandα-SMA in liver tissue and the percentage of the area of collage in rats treated with rosiglitazone at the eighth week were not significantly changed compared with the rats treated with rosiglitazone at the sixth week(P＞0.05),but the expression of TGF-β1 in liver tissue was decreased significantly(P＜0.01).The expression of PPARγin liver tissue is relative both to the expression ofα-SMA in liver tissue significantly (r=0.714,P＜0.001),and to the expression of TGF-β1 in liver tissue(r=0.492,P＜0.01).Conclusions:With the development of liver fibrosis,the expression of PPARγwas decreased gradually in liver tissue.Rosiglitazone has protective effect on liver injury,it can inhibit hepatic fibrosis induced by porcine serum in rats and upregulate the expression of PPARγ.The mechanism may be associated with the effect of down-regulating TGF-β1 andα-SMA and result in suppressing the activation of hepatic stellate cells.The PPARγcan suppress the activation of the hepatic stellate cell and can suppress the development of the hepatic fibrogensis. |
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