Study Of JJSJS And Its Insect Drugs On TGF-β/Smads And MMPs/TIMPs Of Hepatic Fibrosis In Rats

Objective:To obsreve the effect of SJS and its parts on transforming growth factor beta/smad pathway(TGF-β/Smad),tumor necrosis factor alpha(TNF-α) and matrix metalloproteinases/tissue inhibitor of metalioproteinases(MMP/TIMP) of hepatic tissue of hepatic fibrosis rats and to discuss the curative and mechanism of jiajiansanjiasanfang on the treatment of hepatic fibrosis.Methods:Male SD rats were randomized into 6 groups:normal control group, model group, positive control group, JJSJS group, insect drugs group and expel insect drugs group. Except the rats in the normal group, others were inflicted with hepatic fibrosis by intraperitoneal injection of 40% carbon tetrachloride, and were given medication at the same time. After eight weeks, all the rats were excuted and the hepatic tissues were kept for pathologic examination to observe hepatic fibrosis and immunohistochemical to detect TGF-β1, Smad2/3, Smad7 and TNF-α, and in situ hybridization to detect MMP-2, TIMP-2, TIMP-1.Results:1.TGF-β/Smad pathway:Expression of TGF-β1 in hepatic tissue:TGF-β1 expression scarcely appeared in the hepatic tissues of rats in the normal group, but increased visibly in rat liver of the model group(P<0.01).Compared with the model group, their expression decreased in rat liver of the positive control group(P<0.05) and the JJSJS group(P<0.01),but the expression of insect drugs and expel insect drugs groups increased.Expression of Smad2/3 in hepatic tissue:Smad2/3 expression scarcely appeared in the hepatic tissues of rats in the normal group, but increased visibly in rat liver of the model group(P< 0.01).Compared with the model group,their expression decreased in rat liver of the positive control group and the JJSJS group(P<0.01).Compared with the positive control group, the JJSJS group is more lower(P<0.05). but the expression of insect drugs and expel insect drugs groups increased.Expression of Smad7 in hepatic tissue:Compared with the normal group, Smad7 expression decreased visibly in the hepatic tissues of rats in the model group. Compared with the model group, the expression increased visibly in the JJSJS one(P<0.01),but didn't have difference with the positive control one. Compared with the JJSJS group, their expression increased visibly in rat liver of the insect drugs and expel insect drugs groups(P<0.01).Expression of TNF-αin hepatic tissue:TNF-αexpression scarcely appeared in the hepatic tissues of rats in the normal group, but increased visibly in rat liver of the model group(P< 0.01).Compared with the model group,their expression decreased in rat liver of the positive control group and the JJSJS group(P<0.01).But the expression of insect drugs and expel insect drugs groups increased.2.MMP/TIMP System:Expression of MMP-2mRNA in hepatic tissue; Compared with the normal group, expression of MMP-2mRNA in hepatic tissue didn't have difference with it in the model group, and the expression increased in the insect drugs group(P<0.05).Compared with the model group, the expression increased in the insect drugs group (P<0.05)while there was not different in the others.Expression of TIMP-2mRNA in hepatic tissue:Compared with the normal group, expression of MMP-2mRNA in hepatic tissue increased visibly in the model group(P<0.01).Compared with the model group, the expression decreased in the other groups(P<0.01).Compared with the positive control group, the expression decreased in the JJSJS group(P<0.01) and the insect drugs groups(P<0.05),and lower in the JJSJS group.Expression of TIMP-1 mRNA in hepatic tissue:Compared with the normal group, the expression of TIMP-1 mRNA in hepatic tissue increased visibly in the model group(P< 0.01).Compared with the model group the expression all decreased in the other groups(P< 0.01),and compared with the positive control group, the expression decreased in the JJSJS and the insect drugs group(P<0.05). Conclusions:1. JJSJS reduces the fibrotic degree of rats hepatic tissue significantly which means that this formular has powerful anti-fibrosis effect.2. JJSJS inhibits expression of TGF-β1 and Smad2/3 in hepatic tissues and increases the expression of Smad7.It is better than the colchicines.It has powerful anti-fibrotic effect through inhibiting the TGF-β/Smad pathway.3. There isn't different between the JJSJS and the colchicines in decressing the expression of TNF-a in hepatic tissue in the fibrosis rats.4. JJSJS decresses the expression of TIMP-lmRNA,TIMP-2mRNA and MMP-2mRNA in hepatic tissue in the fibrosis rats, so it suppresses ECM's degradation process by decresses the expression of MMP-2mRNA.5. It has not difference between the JJSJS and the insect drugs group in decressing the expression of TIMP-lmRNA.