18α-Glycyrrhizin induces apoptosis and suppresses activation of rat hepatic stellate cells
18α-Glycyrrhizin induces apoptosis and suppresses activation of rat hepatic stellate cells
复制标题
18α-甘草甜素诱导大鼠肝星状细胞凋亡并抑制活化
DOI：
10.12659/msm.882196
复制
发表时间：
2012-01-01
影响因子：
3.1
通讯作者：
Lu, Lun-Gen
中科院分区：
文献类型：
--
作者：
Qu, Ying;Chen, Wei-Hua;Lu, Lun-Gen
背景：探讨18α甘草酸苷对大鼠肝星状细胞和肝细胞保护作用的可能机制。材料/方法：SD大鼠随机分为5组：正常对照组、肝纤维化模型组、18α甘草酸高剂量组(25 mg/kg/d)、18α甘草酸中剂量组(12.5 mg/kg/d)和18α甘草酸低剂量组(6.25 mg/kg/d)。以四氯化碳(CCl4)诱导大鼠肝纤维化模型。结果：18α甘草次酸呈剂量依赖关系抑制CCl4诱导的肝纤维化。肝纤维化组和18α-GL治疗组的α-SMA的mRNA和蛋白表达均有显著差异，提示18α-GL可抑制HSC的增殖和活化。肝纤维化组肝门管区和纤维间隔仅见少量肝星状细胞凋亡。α-SMA和TUNEL双色染色显示18个α-GL处理组HSC凋亡率增加。纤维化组核因子-kappaB主要分布于胞核，18αGL组核因子-kappaB主要在胞浆表达。在体外实验中，18αGL促进肝细胞增殖，但抑制HSCs的增殖。结论：18α-GL可通过阻断核转录因子-kappaB的核内移位，抑制HSCs的活化，诱导HSCs的凋亡，这在18α-GL的抗肝纤维化作用中起重要作用。
Background: To investigate the potential mechanisms underlying the protective effects of 18 alpha Glycyrrhizin (GL) on rat hepatic stellate cells (HSCs) and hepatocytes in vim and in vitro.Material/Methods: Sprague-Dawley (SD) rats were randomly divided into 5 groups: normal control group, liver fibrosis group, high-dose 18 alpha GL group (25 mg/kg/d), intermediate-dose 18 alpha GL group (12.5 mg/kg/d) and low-dose 18 alpha GL group (6.25 mg/kg/d). The rat liver fibrosis model was induced by carbon tetrachloride (CCl4). The expressions of a-smooth muscle actin (alpha SMA) and NF-kappa B were determined by real-time PCR and immunohistochemistry.Results: 18 alpha GL dose-dependently inhibited the CCl4-induced liver fibrosis. There were significant differences in the mRNA and protein expressions of alpha SMA between the fibrosis group and 18 alpha-GL treatment groups, suggesting that 18 alpha GL can suppress the proliferation and activation of HSCs. Few HSCs were apoptotic in the portal area and fibrous septum in the liver fibrosis group. However, the double-color staining of a-SMA and TUNEL showed that 18 alpha-GL treatment groups increased HSC apoptosis. NF-kappa B was mainly found in the nucleus in the fibrosis group, while cytoplasmic expression of NF-kappa B was noted in the 18 alpha GL groups. In the in vitro experiments, 18 alpha GL promoted the proliferation of hepatocytes, but inhibited that of HSCs. HSCs were arrested in the G2/M phase following 18 alpha GL treatment and were largely apoptotic.Conclusions: 18 alpha-GL can suppress the activation of HSCs and induce the apoptosis of HSCs by blocking the translocation of NF-kappa B into the nucleus, which plays an important role in the protective effect of 18 alpha-GL on liver fibrosis.