摘要
目的探讨不同剂量环孢霉素A(cyclosporine A,CsA)对大鼠心脏功能的影响以及钙调神经磷酸酶(calcineurin,CaN)活性、mRNA表达与心功能的关系。方法 70只健康纯系Wistar大鼠,体质量(200±25)g, 随机分为A、B、C、D组及正常对照组,每组14只。A、B、C、D组分别给予CsA 5．0、12．5、25．0、50．0 mg·kg-1·-1灌胃,对照组用4 ml生理盐水灌胃。持续给药2、4周后每组各取7只进行心脏超声检测心脏功能、病理形态学、 CaN活性及RT-PCR方法检测(CaNAB mRNA的表达。结果与正常组比较,用药各组随剂量增加心脏功能降低,左室射血分数(LVEF)下降(P<0．01),左室短轴缩短率(FS)下降(P<0．01),A、B、C组左心室(LV)增大,B、 C组左心房(LA)也增大(P<0．05)。随着药物剂量增加,病理改变为心肌变性损伤加重。用药各组2周时(CaN 活性随药物剂量增加而下降(F=27．19,P<0．05),而4周时B、C组CaN活性均较2周时升高(P<0．05); CaNAB mRNA表达随着用药剂量和用药时间增加而下降(P<0．01)。结论大剂量CsA对心肌细胞损伤发生的早而且严重,心脏功能下降明显。
Objective To evaluate the effect of cyclosporine A（CsA） on the normal rat myocardium heart function and calcineurin （CAN） activity and CaNAβ mRNA expression. Methods Seventy wistar rats were divided into A,B,C,D and control groups according to the doses of CsA. 2 and 4 weeks after CsA 5.0,12.5,25.0,50.0 mg·kg^-1·d^-1 was gastrically instilled into A,B,C and D groups for 2 and 4 weeks, the pathological changes were observed. Colorimetric assay was applied for determining CaN enzyme activity. The information of rat left ventricle （LV） and left atrium （LA） value obtained from echocardiography was recorded and CaNAβ mRNA products by RT-PCR were detected. Results CsA suppressed heart function by observing both echocardiographic changes and histopathological myocardial degeneration ,left ventricle ejection fraction （LVEF,P 〈 0.01 ） and fraction short（FS, P 〈 0.01） were detected, the enlargement of LV of A,B or C groups and LA of B,C groups （P 〈 0.05） were observed. There was a significant surpress for CaN activity during the 2-week treatment with CsA （F = 27.19,P 〈 0.05） ,but it was increased after 4 weeks （P 〈 0.05）. The expression of CaNAβ mRNA was decreased along with the increase of dose and time （P 〈 0.01 ）. Conclusions A large dose of CsA administration may cause early and severe injuries of myocytes as well as a decrese of cardiac function. Studies suggest that inter mitochondfial calcium overload caused by CsA may possibly be the key to its devastating effect.
出处
《中国地方病学杂志》
CAS
CSCD
北大核心
2006年第3期260-263,共4页
Chinese Jouranl of Endemiology
基金
黑龙江省自然科学基金资助项目(ZJY2004-03)哈尔滨医科大学博士创新基金资助项目(2003)
