摘要
目的 比较研究氯化钴（CoCl2）对裸鼹鼠及C57BL/6J小鼠肝星形细胞增殖和凋亡的影响.方法 采用活细胞计数试剂盒（CCK8）法和流式细胞术分别检测不同浓度CoCl2对裸鼹鼠和小鼠肝星形细胞增殖活力以及和凋亡水平的影响.采用蛋白印迹测定CoCl2处理后裸鼹鼠肝星形细胞低氧诱导因子1α（HIF-1α）和凋亡相关蛋白（BCL2、BAX）的表达水平.结果 低浓度（50 μtmol/L）CoCl2对C57BL/6j、鼠肝星形细胞增殖活性具有明显的抑制作用,并能显著提高其凋亡率,然而同样剂量的CoCl2能够显著提高裸鼹鼠肝星形细胞的增值活性,对细胞凋亡率亦无明显影响.高剂量CoCl2（＞200 μtmol/L）虽能导致裸鼹鼠肝星形细胞增殖活力的降低,及凋亡率的升高,但裸鼹鼠肝星形细胞的变化幅度明显小于小鼠.同时CoCl2处理后,裸鼹鼠肝星形细胞HIF-1α的表达或累积显著升高（P＜0.05）,BCL2/BAX比率显著上调（P＜0.05）.结论 与C57BL/6J小鼠相比,裸鼹鼠肝星形细胞具有更强的抵抗CoCl2引起的化学性低氧损伤的能力.同时HIF-1α可能参与调控裸鼹鼠抵抗化学性低氧环境造成的损伤.
Objective To compare and study the influence of cobalt chloride （COCl2） on proliferation and apoptosis of hepatic stellate cells in the naked mole rat and C57BL/6J mouse, and preliminarily investigate the possible mechanism of hypoxic tolerance in naked mole rat. Methods Evaluating the effects of different concentrations of COCl2 on proliferation activity and apoptosis level of hepatic stellate cells in the naked mole rat and mouse by Cell Counting Kit-8 assay （CCK8） and flow cytometry. Detect the expression of hypoxia inducible factor 1 α （HIF-1 α） and apoptosis-related proteins （BCL2, BAX）of hepatic stellate cells in the naked mole rat after COCl2 treatment by Western blot assay. Results COCl2 significantly inhibited the proliferation and increased the apoptotic rate of hepatic stellate cells in C57BL/6j mice at a low concentration of 50 μmol/L. However, a same dose of COCl2 can significantly improve the proliferation of hepatic stellate ceils in the naked mole rat but had no significant effect on its apoptotic rate. While high concentrations of COCl2 （〉 200 μmol/L） showed a inhibition of proliferation and a rise of apoptotic rate of hepatic stellate cells in naked mole rat and mice, but the CoCl2-induced changes in hepatic stellate cells of the naked mole rat were much smaller than those of mice. Simultaneously, the expression of HIF-1 α and the ratio of apoptosis-related proteins （BCL2/BAX） in hepatic stellate cells of the naked mole rat upregulated or accumulated significantly after treating with COCl2 （P〈0.05）. Conclusion Compared with C57BL/6J mice, the naked mole rat hepatic stellate cells had a greater ability of resistance to hypoxic damage caused by COCl2. It was speculated that HIF-1 α may be involved in the regulation of resistance to damage caused by hypoxic environment in naked mole rat.
出处
《实验动物与比较医学》
CAS
2016年第1期66-71,共6页
Laboratory Animal and Comparative Medicine
基金
国家科技支撑计划课题（2015BAI09B02）、国家自然科学基金（31402028）、上海市科委基金（14140900200,13140900400）、全军实验动物专项课题[SYDW（2014）007]联合资助
