慢性间歇性低压低氧抑制线粒体途径介导的代谢综合征大鼠心肌组织细胞凋亡  

Chronic intermittent hypobaric hypoxia ameliorates myocardial apoptosis through inhibiting mitochondrial pathway in rats with metabolism syndrome

作　　者：袁芳[1] 李艳青[2] 滕旭[1,3] 周京京[1] 郭赞[1] 王昕[1] 张自伟[4] 张翼[1] 

机构地区：[1]河北医科大学生理学教研室,河北石家庄050017 [2]河北省中医院妇科,河北石家庄050011 [3]河北省重点实验动物实验室,河北石家庄050017 [4]河北医科大学第一医院,河北石家庄050030

出　　处：《中国药理学通报》2015年第8期1131-1136,共6页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No 31071002;31271223;81100229);河北省自然科学基金资助项目(No C2012206001;C2012206063);河北省科技厅科技支撑项目(No 12276104D40;11246125D);河北省卫生厅医学研究重点项目(No 20090319);河北省科技厅项目(No122777158)

摘　　要：目的 证实CIHH（chronic intermittent hypobaric hypoxi-a,CIHH）具有改善代谢综合征（metabolism syndrome,MS）大鼠心肌细胞凋亡的作用,并探讨其机制。方法 10%果糖水喂养SD大鼠（250~300）g42d制备MS模型,检测动脉血压以及空腹血糖、胆固醇、甘油三酯和胰岛素含量,HE染色观察心肌结构,TUNEL染色和caspase-3活性测定检测心肌细胞凋亡,Westernblot检测Bcl-2和Bax的蛋白表达水平。结果 与正常大鼠比较,果糖喂养大鼠表现出明显的高血压、高血糖、高甘油三脂血症、高胆固醇血症和高胰岛素血症,心肌结构损伤。TUENL染色显示凋亡的心肌细胞数量明显增加,心肌组织caspase-3活性明显升高。Bcl-2蛋白表达明显降低,Bax蛋白表达明显上调,Bcl-2/Bax比值明显下降。有意义的是CIHH能够明显改善MS大鼠上述改变。而且,单纯CIHH组大鼠的上述指标与对照组大鼠无差异。结论CIHH能够明显改善MS大鼠心肌细胞凋亡,其作用可能与抑制凋亡的线粒体途径有关。可能为研究MS患者心功能异常的治疗和预防提供新的靶点和思路。Aim To confirm the inhibitory effect of chronic intermittent hypobaric hypoxia （CIHH） on my- ocardial apoptosis induced by metabolism syndrome （MS）, and to investigate its mechanism. Methods A rat model of MS induced by fructose was used. The blood pressure and the plasma content of glucose, tri-glyceride, cholesterol, and insulin after 12 h fasting were detected. HE stain were used to detect the cardi- ac structure. The TUNEL staining and activity of caspase-3 were used to detect the apoptosis of myocar- dium. The protein expression of Bcl-2 and Bax was detected by Western blot. Results Compared withthe control rats, the blood pressure and the plasma content of glucose, triglyceride, cholesterol, and insu- lin were all increased in rats with MS. In rats with MS, the impairment of cardiac structure and the increase of apoptosis were also observed. The protein expression of Bcl-2 was significantly down-regulated, and that of Bax was significantly up-regulated in MS rats. The ratio of Bcl-2/Bax was also significantly decreased. Interest- ingly, CIHH could ameliorate all of the above issues.There was no significant difference between control group and CIHH group. Conclusion CIHH may im- prove the increased apoptosis in rats with MS via inhib- iting the mitochondrial pathway of apoptosis. This stud- y might provide new targets for therapy and the preven- tion of MS patients.

关 键 词：慢性间歇性低压低氧 代谢综合征 心肌 凋亡 Bcl-2 BAX 

分 类 号：R-332[医药卫生] R322.11