18α-甘草酸对四氯化碳诱导的肝纤维化大鼠TGF-β1/Smad信号通路的影响

Effects of 18α-glycyrrhizin on TGF-β1/Smad signaling pathway in rats with carbon tetrachloride-induced liver fibrosis.

作者信息

Qu Ying, Zong Lei, Xu Mingyi, Dong Yuwei, Lu Lungen

机构信息

Department of Gastroenterology, Shanghai First People's Hospital, Shanghai Jiaotong University School of Medicine Shanghai 200080, China.

出版信息

Int J Clin Exp Pathol. 2015 Feb 1;8(2):1292-301. eCollection 2015.

PMID:25973013

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4396252/

Abstract

BACKGROUND

Glycyrrhizin has various pharmacological effects including hepato-protection. This study aimed to investigate the potential mechanism underlying the protective effects of 18α-glycyrrhizin (18α-GL) in rats with carbon tetrachloride (CCl4) induced liver fibrosis.

METHODS

Male Sprague-Dawley (SD) rats were randomly divided into control group, fibrosis group, 25 mg/kg 18α-GL group and 12.5 mg/kg 18α-GL group. Rats in experimental groups were subcutaneously injected with 40% CCl4 twice weekly for 8 weeks. Immunohistochemical examination was carried out to detect the protein expressions of collagen I, collagen III, TGF-β1, p-Smad2, p-Smad3, Smad 7 and SP-1, in the liver, and the mRNA and protein expressions of these genes were determined in the liver by real time PCR and Western blot assay, respectively.

RESULTS

18α-GL ameliorated histological changes and significantly suppressed collagen deposition. 18α-GL significantly decreased the mRNA expressions of TGF-β1, Smad2, Smad3 and SP-1 in the liver. Immunohistochemical staining revealed that TGF-β1, p-Smad2, p-Smad3 and SP-1 expressions reduced following 18α-GL therapy. Western blot assay showed p-Smad2, p-Smad3, smad2 and smad3 expressions decreased after 18α-GL treatment. The mRNA and protein expression of Smad7 remained unchanged.

CONCLUSION

18α-GL is able to attenuate CCl4 induced liver fibrosis in rat.

摘要

背景

甘草酸具有多种药理作用，包括肝脏保护作用。本研究旨在探讨18α-甘草酸（18α-GL）对四氯化碳（CCl4）诱导的大鼠肝纤维化保护作用的潜在机制。

方法

将雄性Sprague-Dawley（SD）大鼠随机分为对照组、纤维化组、25mg/kg 18α-GL组和12.5mg/kg 18α-GL组。实验组大鼠每周皮下注射40% CCl4两次，共8周。采用免疫组织化学法检测肝脏中I型胶原、III型胶原、转化生长因子-β1（TGF-β1）、磷酸化Smad2（p-Smad2）、磷酸化Smad3（p-Smad3）、Smad7和SP-1的蛋白表达，并分别通过实时荧光定量PCR和蛋白质印迹法检测肝脏中这些基因的mRNA和蛋白表达。

结果

18α-GL改善了组织学变化，并显著抑制了胶原沉积。18α-GL显著降低了肝脏中TGF-β1、Smad2、Smad3和SP-1的mRNA表达。免疫组织化学染色显示，18α-GL治疗后TGF-β1、p-Smad2、p-Smad3和SP-1的表达降低。蛋白质印迹法显示，18α-GL治疗后p-Smad2、p-Smad3、Smad2和Smad3的表达降低。Smad7的mRNA和蛋白表达保持不变。

结论

18α-GL能够减轻CCl4诱导的大鼠肝纤维化。

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