环孢霉素A诱导心肌损伤与钙敏感受体表达关系的研究.docVIP

  环孢霉素 A 诱导心肌损伤与钙敏感受体 表达关系的研究# 迟锦玉，朱烨静，韩磊，赵德超，尹新华** 5 10 15 20 25 30 35 40 （哈尔滨医科大学附属第一医院，哈尔滨 150000） 摘要：目的：探讨环孢霉素 A（CyclosporinA, CsA）诱导的心肌损伤与钙敏感受体（Calcium sensing receptor, CaSR）表达的关系。方法：原代培养的乳鼠心肌细胞，加入不同时间（4、 8、12、24、48h）、不同剂量（5、10、20、40、80μg/ml）的 CsA，应用相差显微镜观察 心肌细胞形态变化，采用 RT-PCR、Western blot 技术，分别探测各组中 CaSR mRNA 以及蛋 白的表达情况。结果：与对照组相比，随着 CsA 作用时间延长、剂量增加，心肌细胞胞浆内 颗粒逐渐增多，收缩性逐渐减弱；RT-PCR 及 Western blot 结果显示，与对照组比较，给予 10μg/ml CsA 作用 4h 后心肌细胞 CaSR 表达开始增加，具有统计学意义（p﹤0.05），随着 时间延长、剂量增加，CaSR 表达呈抛物线形变化，即损伤初期 CaSR 一度随时间延长、剂量 增大表达增多，但是损伤后期，随着损伤不断加重，CaSR 表达较前减少。结论：CsA 呈时间、 剂量依赖性诱导心肌细胞损伤，这种损伤作用与 CaSR 表达变化密切相关，本研究可能为 CsA 诱导的心肌损伤的防治提供新靶点。 关键词：心血管内科学；环孢霉素 A；钙敏感受体；心肌细胞损伤 中图分类号：R992 The relation of cyclosporin A -induced cardiomyocyte injury and the calcium -sensing receptor CHI Jinyu, ZHU Yejing, HAN Lei, ZHAO Dechao, YIN Xinhua (The First Affiliated Clinical College, Harbin Medical University, Harbin 150000) Abstract: Objective: To explore whether CsA-induced myocardial injury is related to CaSR expression. Methods: The cultured neonatal rat cardiomyocytes were treated with CsA, at different time (4,8,12,24,48h) and dose (5,10,20,40,80μg/ml), the morphological changes were observed by phase-contrast microscopy, CaSR mRNA expression were determined by RT-PCR, and CaSR protein expression were determined by western blot. Results: The phase-contrast microscopy observation showed that compare to the control group, at different times and doses after CsA treatment, the cytoplasmic particles gradually increased, and the contraction weakened; CaSR mRNA and protein expression increased at 4h after 10μg/ml CsA treatment (p0.05)，however， with the increasing injuries, the expression of CaSR decreased. Conclusions: The results demonstrated that CsA induced cardiomyocyte injury in a time and dose-dependent manner. Moreover, CsA-induced cardiomyocyte injury could be related to CaSR expression. Our findings might provide a new insight into the mechanisms involved in CsA-induced myocardial injury.