[1]周玉燕,孙玉,李萍,等.莫诺苷通过抗氧化应激保护雷公藤甲素所致肝细胞凋亡[J].南方医科大学学报,2018,(08):949.
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莫诺苷通过抗氧化应激保护雷公藤甲素所致肝细胞凋亡()
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《南方医科大学学报》[ISSN:1673-4254/CN:44-1627/R]

卷:
期数:
2018年08期
页码:
949
栏目:
出版日期:
2018-07-31

文章信息/Info

Title:
Monoside antagonizes triptolide-induced hepatocyte apoptosis via the anti-oxidative stress pathway
作者:
周玉燕孙玉李萍秦国正程倩刘宇陈滢俐王国栋
关键词:
雷公藤甲素莫诺苷肝损伤抗氧化应激
Keywords:
monoside triptolide liver injury anti-oxidative stress
摘要:
目的观察具有抗氧化应激活性的环烯醚萜苷化合物莫诺苷对雷公藤甲素(TP)诱导的肝损伤的保护作用及其分子机制。 方法雷公藤甲素,莫诺苷分别单独及联合给药小鼠及人肝癌HepG2细胞后,血清学法测定各组小鼠肝生化指标的变化;MTT 法检测各实验组对HepG2细胞生长抑制率的影响;激光共聚焦显微镜观察各组细胞形态的变化;流式细胞术检测各组细胞凋亡 率;WB法检测氧化应激通路中关键蛋白的表达。结果动物实验表明雷公藤甲素具有很明显的肝脏损伤作用,小鼠血清中肝 生化指标及肝脏指数的水平显著升高(P<0.05);细胞实验则表明其抑制了HepG2 细胞的生长,24 h 细胞的生长活性仅为 72.83%,并随时间增长而降低。细胞凋亡明显,细胞核破裂皱缩,24 h细胞凋亡率高达43.1%。此外,氧化应激通路相关蛋白 Nrf2,HO-1 的表达明显降低。而莫诺苷联合用药后逆转了以上实验指标,使得小鼠中肝生化指标及肝脏指数显著下降(P< 0.05),肝细胞的凋亡率,细胞形态及氧化应激相关通路蛋白的表达都得到了明显改善(P<0.05)。结论莫诺苷可保护雷公藤甲 素诱导的肝损伤,其机制可能与抗氧化应激有关。
Abstract:
Objective To investigate the protective effect of monoside against triptolide-induced liver injury and explore its molecular mechanism. Methods BALB/C mice treated with gastric lavage with triptolide and monoside, either alone or in combination, were examined for changes of hepatic biochemical parameters using the serological method. The growth inhibition rate of HepG2 cells treated with triptolide or monoside or both was assessed with MTT assay, and the cell morphological changes were observed using laser confocal microscopy; the expressions of the target proteins in the antioxidative stress pathway were detected using flow cytometry and Western blotting. Results In BALB/C mice, gastric lavage of triptolide induced obvious hepatic damage. In HepG2 cells, treatment with triptolide significantly inhibited the cell growth, resulting in a cell viability as low as 72.83% at 24 h; triptolide also induced obvious cell apoptosis and cell nucleus deformation, causing an apoptosis rate of 43.1% in the cells at 24 h. Triptolide significantly reduced the expressions of Nrf2 and HO-1 proteins related with the oxidative stress pathway. Combined treatment with morroniside obviously reversed these changes, resulting in significantly decreased hepatic biochemical parameters and the liver index in BALB/C mice and in significantly lowered cell apoptosis rate, improved cell morphology, and increased Nrf2 and HO-1 protein expressions in HepG2 cells. Conclusion Monoside protects against triptolide-induced liver injury possibly by relieving oxidative stress.

相似文献/References:

[1]陈将华,郑维威,姜旭东,等.雷公藤甲素通过抑制逆转录病毒HERV-K Np9基因转录诱导人急性T淋巴细胞白血病Jurkat细胞凋亡[J].南方医科大学学报,2015,(05):702.

更新日期/Last Update: 1900-01-01