摘要
目的 探讨洛沙坦对糖尿病大鼠肾脏肥大的影响及其与肾小球周期素激酶抑制剂P2 7水平的关系。 方法 腹腔注射链脲佐菌素建立糖尿病 (DM )模型并分别给予生理盐水、洛沙坦1mg·kg-1·d-1或 2mg·kg-1·d-1灌胃 8周。Western杂交方法测定肾小球裂解液P2 7蛋白水平 ,ELISA方法测定肾小球裂解液细胞外基质 (ECM )蛋白 (Ⅳ型胶原及纤维连接蛋白 )和尿白蛋白 ,采用图象分析系统测定肾小球面积。 结果 DM 8周大鼠肾重 /体重比例增高 ,肾小球面积增大 ,肾小球ECM蛋白水平增加 ,2 4h尿白蛋白排泄增多 ,同时肾小球P2 7水平增高。洛沙坦降低DM大鼠肾重 /体重比例、肾小球面积及肾小球ECM蛋白水平 ,减少 2 4h尿白蛋白排泄 ,降低肾小球P2 7水平。洛沙坦的上述作用随剂量的增加而增强。洛沙坦不改变DM大鼠血糖水平。 结论 洛沙坦可减轻DM大鼠肾小球肥大程度 ,此作用可能与洛沙坦降低DM大鼠肾小球P2
Objective To investigate the relationship between the cyclin kinase inhibitor P27 and the protecting effect of Losartan on the diabetic glomerulus. Methods STZ induced diabetic rats were given Losartan (1 mg·kg -1 ·d -1 or 2 mg·kg -1 ·d -1 )for 8 weeks.The P27 protein of glomerular lysate was detected with western blot analysis. The extracellular matrix (ECM) protein (type Ⅳ collagen and fibronectin) of glomerular lysate and 24 h urine albumin were examined with ELISA. Image analysis system was used to detect area of glomerulus. Results Glomerular area and ratio of kidney weight to body weight elevated in diabetic rats. Meanwhile, the 24 h urine albumin excretion, glomerular ECM and glomerular P27 protein increased in diabetic rats. Losartan decreased glomerular area, the ratio of kidney weight to body weight, 24 h urine albumin excretion as well as glomerular P27 level in diabetic rats. The above effect of Losartan increased as the dose of Losartan increased. The blood glucose remained constant in diabetic rats and Losartan treated diabetic rats. Conclusion Losartan can ameliorate diabetic glomerular hypertrophy through decrement of glomerular P27 level.
出处
《中国糖尿病杂志》
CAS
CSCD
2003年第5期341-343,共3页
Chinese Journal of Diabetes
