Oridonin对急性肝衰竭小鼠肝细胞凋亡的影响及其机制研究*

doi:10.3969/j.issn.1672-5069.2017.04.005

实用肝脏病杂志 ›› 2017, Vol. 20 ›› Issue (4): 397-401.doi: 10.3969/j.issn.1672-5069.2017.04.005

Oridonin对急性肝衰竭小鼠肝细胞凋亡的影响及其机制研究^*

邓怡林, 于合国, 施敏, 石翠翠, 范建高, 李光明

200092 上海市上海交通大学医学院附属新华医院消化内科（邓怡林,石翠翠,范建高,李光明）; 附属同仁医院消化内科（施敏）; 上海市计划生育科学研究所（于合国,刁华）

收稿日期:2016-11-17 出版日期:2017-07-10 发布日期:2017-07-07
通讯作者: 李光明，E-mail: ligm68@126.com
作者简介:邓怡林，女，25，硕士研究生。主要从事肝损伤及肝纤维化的防治研究
基金资助:
国家自然科学基金资助项目（编号：81400631/81570549）

Suppression of TNF-α and JNK-related pro-apoptotic signaling expression of oridonin in mice with LPS/D-Gal-induced acute liver failure

Deng Yilin, Yu Heguo, Shi Min, et al.

Department of Gastroenterology,Xinhua Hospital Affiliated to Jiaotong University School of Medicine, Shanghai 200092,China

Received:2016-11-17 Online:2017-07-10 Published:2017-07-07

摘要/Abstract

摘要： 目的探讨冬凌草甲素（oridonin）对脂多糖/D-氨基半乳糖氨（LPS/D-Gal）联合诱导的急性肝衰竭（ALF）小鼠肝细胞凋亡的影响,并探讨其可能的机制。方法取25只小鼠,随机分成5组,每组5只。采用LPS/D-Gal腹腔注射建立小鼠ALF模型,设生理盐水对照组、LPS/D-Gal诱导模型组、LPS/D-Gal诱导和不同剂量oridonin干预组及oridonin处理组。采用末端转移酶介导的缺口末端标记法（TUNEL）检测肝细胞凋亡,采用real-time PCR法检测肝组织TNF-α mRNA水平,采用Western blot法检测凋亡相关蛋白的变化。结果模型组小鼠肝细胞凋亡率为（36.4±1.8） %,显著高于两个oridonin干预组的[（19.4±3.3）%和（11.4±0.3）%,P<0.01];模型组小鼠肝组织TNF-α mRNA水平显著高于正常对照组（P<0.01）,而两个oridonin干预组肝组织TNF-α mRNA水平显著低于模型组（P<0.01）;模型组小鼠线粒体凋亡通路相关的促凋亡蛋白c-Jun氨基末端激酶（JNK）、bax、细胞色素C、cleaved caspase9/3活化水平显著高于两个oridonin干预组（P<0.01）,模型组小鼠抗凋亡蛋白bcl-xl水平显著低于两个oridonin干预组（P<0.01）,模型组小鼠死亡受体凋亡通路相关的促凋亡蛋白caspase8活化水平与两个oridonin干预组并无明显差异（P>0.01）。结论 Oridonin可抑制LPS/D-Gal诱导的ALF小鼠肝细胞凋亡,其机制可能与下调促凋亡细胞因子TNF-α水平和抑制JNK介导的线粒体凋亡信号通路有关。

关键词: 急性肝衰竭, D-氨基半乳糖氨, 冬凌草甲素, 凋亡, 小鼠

Abstract: Objective To investigate the anti-apoptosis effect of oridonin in mice with lipopolysaccharide （LPS）/D-galactosamine（D-Gal）-induced acute liver failure （ALF）. Methods 25 mice were randomly divided into five groups（5 in each）,e.g.,normal,model,oridonin-intervened and oridonin-intervened at different doses,and oridonin for 12 days. ALF model was established in C57BL/6 mice by intraperitoneal injection of LPS/D-Gal. TUNEL,real-time PCR and Western blot were applied to related detection. Results Hepatocyte apoptosis rate in mice in model group was （36.4±1.8）%,significantly higher than that in oridonin-intervened groups [（19.4±3.3）% and （11.4±0.3）%,respectively,P<0.01];administration of oridonin significantly decreased hepatic TNF-α mRNA level in model group （P<0.01）;the expressions of mitochondrial-dependent pro-apoptotic protein such as JNK,bax,cytochrome C,cleaved caspase8/9/3 were upregulated in the model group as compared to in the control group; Pretreatment with oridonin significantly reversed the changes of apoptosis signal pathway induced by LPS/D-Gal, the expression of caspase 8 was not significantly changed and the expression of anti-apoptotic protein bcl-xl increased. Conclusion Oridonin has an anti-apoptosis effect on LPS/D-Gal-induced ALF in mice,and its mechanism may be related to the suppression of pro-apoptotic cytokine TNF-α and JNK-related pro-apoptotic signaling.

Key words: Acute liver failure, D-galactosamine, Oridonin, Apoptosis, Mice

邓怡林, 于合国, 施敏, 石翠翠, 范建高, 李光明. Oridonin对急性肝衰竭小鼠肝细胞凋亡的影响及其机制研究^*[J]. 实用肝脏病杂志, 2017, 20(4): 397-401.

Deng Yilin, Yu Heguo, Shi Min, et al.. Suppression of TNF-α and JNK-related pro-apoptotic signaling expression of oridonin in mice with LPS/D-Gal-induced acute liver failure[J]. JOURNAL OF PRACTICAL HEPATOLOGY, 2017, 20(4): 397-401.

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Oridonin对急性肝衰竭小鼠肝细胞凋亡的影响及其机制研究^*

Suppression of TNF-α and JNK-related pro-apoptotic signaling expression of oridonin in mice with LPS/D-Gal-induced acute liver failure

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