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OBJECTIVE：To investigate the improvement effect of Tiarella polyphylla ethanol extract （TPME）on CCl 4-induced hepatic fibrosis in mice ，and to explore its possible mechanism preliminarily. METHODS ：Totally 60 male Kunming mice were randomly divided into normal group ，model group ，positive control group （colchicine 0.1 mg/kg），TPME low-dose ，medium-dose and high-dose groups （250，500，1 000 mg/kg）according to body weight ，with 10 mice in each group. Except for normal group ， other groups were given 20％ CCl4 olive oil solution intraperitoneally to induce hepatic fibrosis ，twice a week ，for consecutive 8 weeks. From the fifth week after modeling ，administration groups were given relevant medicine intragastrically ，normal group and model group were given constant volume of normal saline intragastrically ，once a day ，for consecutive 4 weeks. Twelve hours after last administration ，the liver weight of mice in each group was measured and the liver index was calculated. The serum contents of ALT，AST，SOD，MDA，PC-Ⅲ，C-Ⅳ，LN，TNF-α and IL- 6 were determined. Western blot assay was used to detect the protein expression of α-SMA，TGF-β1 and Smad 3 in liver tissue. HE and Masson staining were used to observe the pathological changes of hepatic tissue. RESULTS ：Compared with normal group ，the liver index ，the activities of ALT and AST and the contents of MDA ， LN，PC- Ⅲ ，C- Ⅳ ，LN，TNF-α and IL- 6 in serum were increased significantly ， while the activity of SOD was 6011） decreased significantly in model group （P＜0.01）；the protein expression of α-SMA，TGF-β1 and Smad 3 in liver tissues were hfjsznd8@126.com increased significantly （P＜0.01）. Obvious fibrosis lesions was observed in liver tissue. Compared with model group ，the live indexes ，the activities of ALT and AST ，the contents of MDA，PC-Ⅲ，C-Ⅳ，LN，TNF-α and IL-6 in serum were decreased significantly in positive control group and TPME groups ， while the activities of SOD were increased significantly （P＜0.05 or P＜0.01）. The protein expression of α-SMA，TGF-β1 and Smad3 in liver tissue were decreased significantly （P＜0.05 or P＜0.01），and liver fibrosis was improved to different extent. Compared with TPME low-dose group ，the contents of PC- Ⅲ，LN and IL- 6 in serum ，protein expression of TGF-β1 and Smad 3 in liver tissue were decreased significantly in TPME high-dose group （P＜0.05）. CONCLUSIONS ：TPME can improve hepatic fibrosis induced by CCl 4 in mice ，the mechanism of which may be associated with the inhibition of collagen synthesis and oxidative stress，the reduction of inflammatory factors ，and the down-regulation of the expression α-SMA and relative proteins of TGF-β1/ Smad signal pathway.
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Transforming growth factor-β1(TGF-β1)is an important factor in tissue fibrosis. TGF-β1 directly ac- tivates Smad signaling which triggers the overexpression of profibrotic genes. A large number of studies have shown that the dysregulation of TGF-β1/Smad pathway is an important pathogenic mechanism in tissue fibrosis. Smad2 and Smad3 are the two major downstream regulators that promote TGF-β1-mediated tissue fibrosis,whereas Smad7 acts as a nega- tive feedback regulator of the TGF-β1/Smad pathway,blocking TGF-β1-mediated fibrosis. In addition,the recent re- searches have shown that microRNA(miRNA)can regulate the TGF-β1/Smad signaling pathway,and affect the process of tissue fibrosis. This article reviews the role of TGF-β1/Smad signaling pathway in renal,hepatic,pulmonary and myo- cardial fibrosis,as well as the regulation of TGF-β1/Smad signaling pathway by miRNA.
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Objective To observe the influence of total flavonoids from Scutellaria baicalensis (TFSB) on Bleomycin-induced pulmonary fibrosis in rats and investigate the relative mechanism. Methods The pulmonary fibrosis model was established by intratracheal injection of Bleomycin. After 28 d, rats with TFSB treatment by ig administration once a day were killed. The levels of T-AOC, GSH, and MPO in serum were measured and analyzed and the fixed parts of the lung tissue were obtained for HE and Masson staining for histopathological examination. The influences of TFSB on the expression of transforming growth factor-β1 (TGF-β1), Smad2, Smad7, α-SMA, and Collagen I mRNA in lung tissue of rats with Bleomycin-induced pulmonary fibrosis were assayed by RT-PCR. Results Compared with the model group, the levels of T-AOC and GSH in serum were dramatically increased and the level of MPO was decreased remarkably after TFSB treatment; The alveolitis and fibrosis extent were attenuated after TFSB treatment (P< 0.05, 0.01), and the expression levels of TGF-β1, Smad2, α-SMA, and Collagen I mRNA were decreased, and the expression level of Smad7 mRNA was increased (P<0.05, 0.01) significantly. Conclusion TFSB could have mitigable effect on Bleomycin-induced pulmonary fibrosis in rats. The mechanisms might be related to the anti-oxidative damage, the inhibition of activation of inflammatory cell infiltration, and the regulation of TGF-β1/Smad signal pathway.
