氯沙坦对阿霉素肾病大鼠肾脏保护作用的研究

目的 探讨氯沙坦对阿霉素肾病肾脏的保护作用及机制.方法 48只Wistar大鼠随机分为对照组、肾衰组、氯沙坦组,每组16只.肾衰组及氯沙坦组大鼠腹腔注射阿霉素4 mg/kg,每周1次,持续5 w,制作阿霉素肾病大鼠模型;对照组应用同样的方法注射生理盐水.模型复制成功后,氯沙坦组大鼠给予氯沙坦1.2 mg/只灌胃,1 次/d;肾衰组给予同等量生理盐水灌胃,1次/d,均连续给药2 w.生化法检测24 h血尿素氮(BUN)、血肌酐(Cr),化学比色法检测肾皮质中丙二醛(MDA)、超氧化物歧化酶(SOD),RT-PCR方法检测肾组织AT1、AT2、ACE及AGT mRNA表达.结果 与对照组比较,肾衰组血清BUN、Cr均显著升高,肾皮质中MDA升高,SOD降低(P＜0.05);氯沙坦组与肾衰组比较,血清BUN、Cr均显著降低,肾皮质中MDA降低,SOD升高(P＜0.05).与对照组比较,肾衰组肾脏AT1表达上调,AT2降低,AGT和ACE水平增高(P＜0.05);氯沙坦组转为AT1下调,AT2表达接近对照组水平,AGT水平降低,ACE水平降低但仍高于对照组水平(P＜0.05).结论 氯沙坦具有延缓阿霉素肾病大鼠肾功能不全进展,减少氧化应激损伤的保护作用.

Protective effects of Losartan on adriamycin nephrosis rats

Objective To investigate the protecting effect of Losartan on the kidney of the rats with uninephrectomized adriamycin-induced nephrosis and study its possible mechanisms. Methods Experimental nephritic syndrome model was induced with repeated peritoneal injections of adriamycin. Rats were randomly divided into control, model(ADR), losartan (ADR+ARB)groups,respectively. The animal models were injected adriamycin(5 mg/kg) through the abdominal cavityfor 5 w, the control group were injected physiological saline as the same method. The indexes of oxidative stress reaction of the renal cortex, malondialdehyde (MDA), superoxide dismutase (SOD) were measured by chemical chromatometry. The kidney AT1 ,AT2,ACE and AGT mRNA expressions were assayed by RT-PCR. Results Compared with those of control group, the levels of blood urine nitrogen (BUN) and serum creatinine (Cr), MDA were increased, the level of SOD was decreased in ADR group. Compared with those of ADR group, the levels of BUN, Cr and MDA were decreased. The level of SOD was increased in ADR+ARB group. The AT1,ACE and AGT mRNA expressions in ADR group were higher than those of control group. The AT2 mRNA expression was lower than that of control group. The AT1 mRNA expression in ADR+ARB group was lower than that of ADR group, while the AT2 mRNA expression in ADR+ARB group was similar to that in control group. The AGT and ACE mRNA expressions in ADR+ARB group were lower than those of ADR group,while ACE mRNA expression was higher than that of Control group. Conclusions Losarton has protective effects against renal injuries induced by ADR .