| 摘 要： | AIM:To investigate effects of pioglitazone on rat hepaticfibrosis and to explore its mechanism.METHODS:Rat hepatic fibrosis was induced by carbontetrachloride (CCl_4).Forty Sprague-Dawley rats were dividedrandomly into 4 groups:control,model,and two treatment(PⅠ,PⅡ) groups.Except for rats in control group,all ratswere given subcutaneous injection of 400 mL/L CCl_4,twicea wk for 8 wk.Rats in PⅠ and PⅡ groups were also treatedwith pioglitazone of 3 mg/kg,daily via gastrogavagebeginning on the 1~(st) day and at the end of the 2~(nd) week,administration of CCl_4 respectively.Liver functions (ALT,AST),serum fibrotic markers (HA,LN,PCⅣ) and hepatichydroxyproline (HP) concentration were determinedrespectively.Histochemical staining of formalin-fixed liversections with HE,Masson-Trichrome,and immunohistochemicalstaining for α-smooth muscle actin (α-SMA) were performed.Modified Knodell and Chevallier semi-quantitative scoringsystem (SSS) was used to evaluate necroinflammatoryactivity and fibrosis degree.RESULTS:Compared with model group,pioglitazonesignificantly reduced the serum levels of ALT,AST,HA,LNand PCⅢ (P<0.05 or <0.01).The HP concentrations in PⅠ(210.90±24.07 μg/g),and PⅡ (257.36±30.55 μg/g) groups werealso lower than those in model group (317.80±36.44 μg/g)(P<0.01).Histologic examination showed that PⅠ and PⅡgroups had milder hepatocellular degeneration,necrosisand infiltration of inflammatory cells,and thinner or lessfibrotic septa than did model group.The scores fornecroinflammation in PⅠ (2.80±1.03),and PⅡ (3.00±1.05)groups were significantly reduced as compared with modelgroup (4.88±2.30)(P<0.05 or <0.01);the fibrosis scoresin PⅠ(3.40±1.65),and PⅡ (4.60±1.35)groups were alsomarkedly lower than those in model group (7.00±3.21)(P<0.05 or <0.01).Immunohistochemical staining showedthat expression of α-SMA in PⅠ and PⅡ groups wasameliorated dramatically compared with model group.CONCLUSION:PPARγagonist pioglitazone greatly retardsthe progression of rat hepatic fibrosis induced by CCl_4through inhibition of HSC activation and amelioration ofhepatocyte necroinflammation in rats.
|
