摘要
目的:研究不同剂量、不同使用时间的环孢霉素A对肾性高血压大鼠心肌的毒性作用。方法:将37只大鼠随机分为5组,高血压组(n=7):行“一肾一夹(1K1C)”手术;环孢霉素Ⅰ组(n=8):1K1C+环孢霉素A5mg/(kg·d)腹腔注射4周;环孢霉素Ⅱ组(n=8):1K1C+环孢霉素A5mg/(kg·d)腹腔注射6周;环孢霉素Ⅲ组(n=8):1K1C+环孢霉素A20mg/(kg·d)腹腔注射4周;假手术组(n=6)行假手术;观察各组大鼠的血压、体质量、心体质量比及环孢霉素A对心肌组织结构的影响。结果:高血压组大鼠血压、心体质量比犤(185±30)mmHg,(0.35±0.06)%犦明显高于假手术组犤(129±4)mmHg,(0.23±0.02)%犦(t=4.451,P<0.01;t=2.906,P<0.05);环孢霉素Ⅰ组大鼠明显低于手术组和高血压组(t=2.502,P<0.05),对心肌结构无明显损伤;而在环孢霉素Ⅱ组发现心肌明显水肿,线粒体水肿,体质量不升甚至下降等明显毒性作用。结论:环孢霉素A可抑制高血压心肌肥大,但较大剂量或较长时间应用则会产生严重心肌水肿,并且这种作用是剂量、时间依赖性的。
AIM: To study the toxic effect of cyclosporin A(CsA) at different doses and at different applied time on the cardiac tissue of rats with renal hypertension. METHODS:Thirty-seven rats were randomly divided into 5 groups: hypertension group[n=7,“one kidney one clip (1K1C)”operation was performed], CsA Ⅰgroup [n=8, 1K1C+intraperitoneal (ip) injection of CsA 5 mg/kg per day, for 4 weeks], CsA Ⅱgroup (n=8, 1K1C+ip injection of CsA 5 mg/kg per day for 6 weeks), CsA Ⅲgroup(n=8, 1K1C+CsA ip injection of 20 mg/kg per day for 4 weeks) and sham-operated group (n=6).The blood pressure, body mass, ratio of left ventricular mass to body mass, and the effects of CsA on the myocardial structure were observed in all the groups. RESULTS: Blood pressure and ratio of left ventricular mass to body mass of rats in the hypertension group[(185±30)mm Hg,(0.35±0.06)%]were obviously higher than those in the sham-operated group[(129±4) mm Hg, (0.23±0.02)%](t=4.451, P< 0.01; t=2.906, P < 0.05); while those were significantly lower in the CsA Ⅰgroup than in the sham-operated group and hypertension group(t=2.502, P< 0.05), and the myocardial structure was not obviously injured in the CsA Ⅰgroup, while obvious toxic effects were observed in the CsA Ⅱgroup, such as edema in myocardial tissue and mitochondria, no increase even reduce of body mass. CONCLUSION: CsA can inhibit hypertensive cardiac hypertrophy, but large dose or longer period of application will lead to severe myocardial edema, which is dose-dependent and time-dependent.
出处
《中国临床康复》
CSCD
北大核心
2005年第7期38-39,i002,共3页
Chinese Journal of Clinical Rehabilitation
基金
"十五"军队医药卫生科研基金重点课题资助项目(02Z0010)~~
