摘要
研究环孢素A（CyA）引起肾毒性和高血压毒性的可能机制。在培养的大鼠肾小球系膜细胞（MsC），血管平滑肌细胞（SMC）中，加入CyA作用的内皮细胞上清液及内皮素（ET），在光镜下动态观察上述两种细胞的收缩反应，以微尺测量细胞表面面积，并以Fura－2AM荧光负载法测细胞内游离钙（［Ca2+」i）。结果：GyA作用的内皮细胞上清液与ET一样，可使MsC、SMC的细胞内［Ca2+］i明显增加并产生持续的收缩反应。结论：CyA引起肾毒性和高血压毒性的主要机制可能与CyA对内皮细胞的细胞毒作用，导致的以ET为主的诸多血管活性肽的合成和分泌增加，它们作用在MsC、SMC的相应受体，导致肾血流及血压的改变有关。
PURPOSE To study the effect of conditioned media from CyA treated endothelial cell and endothelin(ET)on Ca2+ mobilization and contraction in cultured mesangial cell(MsC) and smooth muscel cell(SMC).METHODS Intracellular free Ca2+ ([Ca2+ ]i ) concentration were measured using Fura-2AM. Cell contraction was evaluated by a digital imaging analysis system.RESULTS Basal concentration of [Ca2+ ]i were not affected by media from endothelial cell; but the conditioned media from CyA 0. 1mg/L for 24 hours treated endothelial cell and ET 0. 1 × 10-6 mol/L significantlyaugmented concentration of [Ca2+ ]i(P<0. 01 ), and induced concomitant contraction of MsC and SMC.CONCLUSIONS These results suggest that cellular mechanisms of CyA- induced nephrotoxicity and hypertension appears at least in part to be an alteration in the pattern of ET release and to act through endothelialreceptor on MsC and SMC, which may contribute to the increase of mean arterial blood pressure and reducingultrafiltration coefficient in CyA nephrotoxicity and hypertension.
出处
《上海医科大学学报》
CSCD
1997年第5期363-366,共4页
Journal of Fudan University(Medical Science)
基金
国家自然科学基金
美国中华医学基金
关键词
环孢素A
高血压
肾毒性
平滑肌细胞
药物疗法
cyclosporin A
hypertension
nephrotoxicity
smooth muscle cell
glomerular mesangial cell
