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|本期目录/Table of Contents|

环孢霉素A对心肌细胞结构和胞内钙离子浓度的影响

《心脏杂志》[ISSN:1009-7236/CN:61-1268/R]

期数:
2010年第4期
页码:
482-485
栏目:
基础研究
出版日期:
2010-06-10

文章信息/Info

Title:
Effect of cyclosporine A on cellular structure and intracellular calcium concentration in neonatal rat cardiomyocytes
作者:
王桂香; 唐洁冰; 傅羽; 刘越; 尹新华
哈尔滨医科大学附属第一临床医学院心内科，黑龙江 哈尔滨 150001
Author(s):
WANG Gui-xiang;  TANG Jie-bing;  FU Yu;  LIU Yue;  YIN Xin-hua
Department of Cardiology, First Hospital, Harbin Medical University, Harbin 150001, Heilongjiang, China
关键词:
环孢霉素A; 心肌细胞; 细胞形态; 钙离子浓度; 大鼠
Keywords:
cyclosporine A;  cardiomyocytes;  morphous;  intracellular calcium concentration
分类号:
R979.5
DOI:
-
文献标识码:
A
摘要:
目的: 探讨不同浓度的环孢霉素A(cyclosporine，CsA)在不同时间点对心肌细胞形态及胞内钙离子浓度(［Ca2+］i)的影响。方法： 分别将 1×10-3 g/L、1×10-2 g/L、2×10-2 g/L的CsA与原代培养的Wistar乳鼠(1~3 d)心肌细胞（n=6）共孵育，于2 h、4 h、6 h、8 h和12 h后，采用相差显微镜观察各组心肌细胞的结构及收缩性；应用激光共聚焦显微镜观察心肌细胞内［Ca2+］i的变化。结果： 不同浓度的CsA作用2 h后，与对照组相比较，各组心肌细胞的形态及收缩性无明显变化。1×10-3 g/L和1×10-2 g/L CsA组心肌细胞内的［Ca2+］i与对照组比较无明显差异；但2×10-2 g/L CsA组心肌细胞内的［Ca2+］i较其他3组明显增加（P<0.01）。作用4 h后，随着CsA浓度的增加，CsA组细胞的收缩性逐渐减弱，胞浆内可见小颗粒逐渐增多；各CsA组心肌细胞内的［Ca2+］i与对照组比较显著增加(P<0.05)；与1×10-3 g/L CsA和对照组相比较，1×10-2 g/L和2×10-2 g/L CsA组增加明显(P<0.05)。作用6 h后，随着CsA浓度的增加，各浓度CsA组与对照组比较，可见细胞内小空泡逐渐增多，细胞的收缩性逐渐减弱。各组心肌细胞内的［Ca2+］i 随着CsA浓度的增加逐渐升高，各组组间具有显著差异（P<0.05）。作用8 h和12 h后，1×10-3 g/L CsA组的心肌细胞出现部分溶解，1×10-2 g/L和2×10-2 g/L CsA组心肌细胞的损伤严重，出现大面积死亡、溶解。结论： CsA可引起原代培养的心肌细胞损伤，收缩性减弱，且具有剂量和时间依赖性，可能与其引起的细胞内［Ca2+］i的增加有关。
Abstract:
AIM: To evaluate the effect of cyclosporine (CsA) on the cellularity and intracellular calcium concentration ［Ca2+］i in neonatal rat cardiomyocytes. METHODS: Neonatal rat cardiomyocytes were prepared from 1- to 3-day-old neonatal Wistar rats. After CsA (1×10-3 g/L, 1×10-2 g/L, 2×10-2 g/L) was gastrically instilled into cardiomyocytes culture media randomly for 2, 4, 6, 8 and 12 h, the cellular structure and contractility were observed under phase-contrast microscope. ［Ca2+］i was measured by a laser scanning confocal microscope with excitation at 488 nm and emission at 530 nm. RESULTS: Compared with control, no obvious difference was observed in the cellularity of cardiomyocytes after incubation at different concentrations of the CsA for 2 h. ［Ca2+］i of cardiomyocytes significantly increased after incubation with CsA 2×10-2 g/L for 2 h compared with that in the other three groups (P<0.01). When the cardiomyocytes were incubated with CsA for 4 h, contractility of the cardiomyocytes was attenuated gradually and more particles were seen. ［Ca2+］i of the cardiomyocytes treated with each concentration of CsA increased compared with control (P<0.05). ［Ca2+］i of the cardiomyocytes treated with CsA 1×10-2 g/L and 2×10-2 g/L increased more significantly compared with that of cardiomyocytes treated with CsA 1×10-3 g/L. With treatment of CsA for 6 h, ［Ca2+］i of cardiomyocytes increased markedly (P<0.05) and more small vacuoles were seen in the cardiomyocytes. With treatment of CsA for 8 and 12 h and the increasing concentration of the CsA, more cardiomyocytes died. CONCLUSION: CsA impairs cardiomyocytes and attenuates contractility of cardiomyocytes in a concentration- and time-dependent manner of CsA. Impairment of the cardiomyocytes may be related to the effect that increased ［Ca2+］i of cardiomyocytes.

参考文献/References

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备注/Memo

备注/Memo:
收稿日期：2010-02-21.基金项目：国家自然科学基金资助（30872387）；国家教育部博士基金资助（200802260006） 通讯作者：尹新华，主任医师，主要从事心血管疾病的治疗以及心血管损伤和再狭窄的研究Email:harbin0910@yahoo.com 作者简介：王桂香，博士生Email：xiangyua6649@eyou.com
更新日期/Last Update: 2010-05-20