甘草酸抑制四氯化碳诱导的大鼠肝损伤中的细胞凋亡和纤维化。

Glycyrrhizic acid inhibits apoptosis and fibrosis in carbon-tetrachloride-induced rat liver injury.

作者信息

Liang Bo, Guo Xiao-Ling, Jin Jing, Ma Yong-Chun, Feng Zheng-Quan

机构信息

Bo Liang, Zheng-Quan Feng, Department of Oncology, Tongde Hospital of Zhejiang Province, Hangzhou 310012, Zhejiang Province, China.

出版信息

World J Gastroenterol. 2015 May 7;21(17):5271-80. doi: 10.3748/wjg.v21.i17.5271.

Abstract

AIM

To investigate anti-apoptotic effects of glycyrrhizic acid (GA) against fibrosis in carbon tetrachloride (CCl4)-induced liver injury and its contributing factors.

METHODS

Liver fibrosis was induced by administration of CCl4 for 8 wk. Pathological changes in the liver of rats were examined by hematoxylin-eosin staining. Collagen fibers were detected by Sirius red staining. Hepatocyte apoptosis was determined by TUNEL assay and the expression levels of cleaved caspase-3, Bax, α-SMA, connective tissue growth factor (CTGF), matrix metalloproteinase (MMP) 2 and MMP9 proteins were evaluated by western blot analysis, and α-SMA mRNA, collagen type I and III mRNA were estimated by real-time PCR.

RESULTS

Treatment with GA significantly improved the pathological changes in the liver and markedly decreased the positive area of Sirius red compared with rats in the CCl4-treated group. TUNEL assay showed that GA significantly reduced the number of TUNEL-positive cells compared with the CCl4-treated group. The expression levels of cleaved caspase-3, Bax, α-SMA, CTGF, MMP2 and MMP9 proteins, and α-SMA mRNA, collagen type I and III mRNA were also significantly reduced by GA compared with the CCl4-treated group (P < 0.05).

CONCLUSION

GA treatment can ameliorate CCl4-induced liver fibrosis by inhibiting hepatocyte apoptosis and hepatic stellate cell activation.

摘要

目的

研究甘草酸(GA)对四氯化碳(CCl4)诱导的肝损伤纤维化的抗凋亡作用及其相关因素。

方法

通过给予CCl4 8周诱导肝纤维化。用苏木精-伊红染色检查大鼠肝脏的病理变化。用天狼星红染色检测胶原纤维。用TUNEL法测定肝细胞凋亡,并用蛋白质印迹分析评估裂解的半胱天冬酶-3、Bax、α-平滑肌肌动蛋白(α-SMA)、结缔组织生长因子(CTGF)、基质金属蛋白酶(MMP)2和MMP9蛋白的表达水平,用实时PCR估计α-SMA mRNA、I型和III型胶原mRNA。

结果

与CCl4处理组大鼠相比,GA处理显著改善了肝脏的病理变化,并显著降低了天狼星红的阳性面积。TUNEL分析表明,与CCl4处理组相比,GA显著减少了TUNEL阳性细胞的数量。与CCl4处理组相比,GA还显著降低了裂解的半胱天冬酶-3、Bax、α-SMA、CTGF、MMP2和MMP9蛋白的表达水平,以及α-SMA mRNA、I型和III型胶原mRNA(P<0.05)。

结论

GA治疗可通过抑制肝细胞凋亡和肝星状细胞活化来改善CCl4诱导的肝纤维化。

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