钙信号因子在缺氧缺水缺食致心脏损伤中作用

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，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。

Role of Ca2+ cell signaling molecules in cardiac injury induced by hypoxia combined with water and dietary depletion in rats

ObjectiveTo investigate the role of Ca²⁺ cell signaling molecules in cardiac injury caused by 10% hypoxia combined with water and dietary depletion in rats.MethodsEighty Wistar rats were randomly divided into a control 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 detect the change of cardiac ultrastructure and immunohistochemistry to detect the expessions of calmodlin(CaM)and cyclic adenosine monophosphate(cAMP) response element binding protein(CREB)at 1st,3rd,5th and 7th day of the experiment in the rats.ResultsAt 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 endothelial cells were also observed.The expressions of CaM(4.22±0.84)in the cytoplasm of myocardial cells were increased 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).ConclusionHypoxia(10% oxygen)combined with water and food depletion might result in damages of struture and function of cadiac cells and the activation of Ca²⁺ cell signaling transduction(increased expression of CaM and phosphorylated CREB may play an important role in the damages.