钙信号因子在缺氧缺水缺食致心脏损伤中作用  

Role of Ca^(2+) cell signaling molecules in cardiac injury induced by hypoxia combined with water and dietary depletion in rats

作　　者：冯新星[1,2] 王丽峰[1] 林仲武[1] 高亚兵[1] 左红艳[1] 徐新萍[1] 李杨[1] 王水明[1] 彭瑞云[1] 王德文[1] 

机构地区：[1]军事医学科学院放射与辐射医学研究所实验病理学研究室,北京100850 [2]中国医学科学院北京协和医学院阜外心血管病医院

出　　处：《中国公共卫生》2014年第6期740-742,共3页Chinese Journal of Public Health

基　　金：国家"709"科技专项(2006FK130006)

摘　　要：目的在观察10%缺氧复合缺水缺食对心脏结构和功能影响的基础上,探讨Ca2+信号转导相关因子在其中的作用。方法将80只Wistar大鼠随机分为对照组、缺氧组、缺食缺水组和缺氧缺食缺水组[置于常压低氧舱(10%氧浓度)并禁食水],于第1、3、5、7天,采用全自动血生化仪检测血清代谢酶改变,透射电镜观察心脏超微结构改变,采用免疫组化检测心肌钙调素和磷酸化环磷酸腺苷反应元件结合蛋白(CREB)表达变化。结果 10%缺氧缺水缺食后7 d,大鼠血清乳酸脱氢酶[(1628.40±460.8)U/L]和谷草转氨酶[(394.60±187.18)U/L]活性明显高于对照组[分别为(578.40±135.04)、(136.40±14.59)U/L];心肌细胞核型不整,染色质边集,核周间隙增宽,线粒体肿胀空化或代偿性增加、Z线紊乱甚至溶解,肌浆网轻度扩张;心肌肌膜肿胀,呈指状突起;间质细胞和血管内皮细胞退变或凋亡;心肌细胞胞浆钙调素(4.22±0.84)与心肌细胞核磷酸化CREB表达(3.57±0.55)明显高于对照组[分别为(0.73±0.41)、(0.90±0.41)]。结论 10%缺氧复合缺水缺食可引起大鼠心脏结构和功能损伤,其机制可能与Ca2+信号通路激活(钙调素和磷酸化CREB表达增加)有关。Objective To investigate the role of Ca2＋ cell signaling molecules in cardiac injury caused by 10% hy- poxia combined with water and dietary depletion in rats. Methods Eighty Wistar rats were randomly divided into a con- trol group,hypoxia group, food and water depletion group, and hypoxia combined with water and food depletion group. The rats with hypoxia were placed in a normbaric chamber with the air containing 10% oxygen. Biochemical methods were adopted to observe the changes of serum metabolic enzymes and transmission electron microscope was used to de- tect the change of cardiac ultrastructure and immunohistochemistry to detect the expessions of caimodlin（CaM） and cyclic adenosine monophosphate（cAMP） response element binding protein （ CREB ） at I st, 3rd, 5th and 7th day of the experi- ment in the rats. Results At 7th day of the experiment, the serum lactic dehydrogenase （LDH） （ 1628. 40 ± 460. 8 U/L） and aspartate aminotransferase（AST） （394. 60 ± 187.18 U/L）increased in the rats of hypoxia combined with water and food depletion compared to those of the control group（578.40± 135.04 and 136. 40 ± 14. 59 U/L） ;the myocardial cells presented irregular shape nucleus, marginated chromatin, increased perinuclear space, swelled mitochondria, increased empty or compensatory mitochondria, Z lines derangement even dissolvement, sarcoplasmic reticulum mild dilation and sarcolemma swelling with finger-like processes;in addition, degeration or apoptosis of interstitial cells and vascular endo- thelial cells were also observed. The expressions of CaM （ 4. 22 ± 0. 84 ） in the cytoplasm of myocardial cells were in- creased and those of phophorylated CREB （ 3.57 ± 0. 55 ） in the nucleus were incresed at 7th day in the rats of hypoxia combined with water and food depletion group compared to those of the control group（ CAM ：0.73 ± 0.41, CREB ：0. 90 ± 0. 41 ）. Conclusion Hypoxia（ 10% oxygen） combined with water and food depletion might result in damages of stru- tu

关 键 词：缺氧缺水缺食 大鼠 心肌 钙调素 环磷酸腺苷反应元件结合蛋白(CREB) 

分 类 号：R541[医药卫生—心血管疾病]