链脲佐菌素诱导的高血糖对大鼠肾、肝及眼睛的影响

Effect of hyperglycemia induced by strepzotozocin on the liver, kidneys and eyes in rats

目的通过不同剂量链脲作菌素(STZ)诱导1型糖尿病大鼠模型,探讨不同高血糖对脏器影响。方法实验分为STZ 40 mg/kg组,50 mg/kg组,60 mg/kg组,25 mg/kg连续3次、每次间隔1 d(25 mg/kg*3)组,空白对照组。给药后0、1、3、7、11、24、48、72 h检测血糖,之后每3 d测量1次,期间观察大鼠一般情况,并于第9周进行血生化以及胰腺、肾、肝及眼睛病理检查。结果 72 h内血糖检测:STZ造模时血糖先轻微升高后降低之后再大幅度升高。50 mg/kg和60 mg/kg组出现给药后第3天死亡现象,存活鼠成模率分别为70%、80%、100%、100%。期间血糖和体质量呈负相关,血糖顺序为:40 mg/kg<50 mg/kg<25 mg/kg*3<60 mg/kg。40 mg/kg组于第10周出现白内障,其他实验组均于第8周出现白内障。第9周血生化检测发现40 mg/kg组insulin、C-Peptide、urea、UA、Cr、ALT、AST、TP、ALB正常,其它实验组均有波动。胰腺、肾、肝病理支持上述改变。结论 25 mg/kg*3诱导高血糖最佳,其成模率高且高血糖稳定;高血糖的并发症的评估要将空腹和随机血糖相结合;不同的高血糖对肾、肝及眼睛影响不同,其中眼睛对高糖反应比较敏感,肾次之,肝影响最小。

Objective To investigate the effect of hyperglycemia induced by different doses of strepzotozocin （STZ） on the liver, kidneys and eyes in rats. Methods Fifty SD rats were divided equally into 5 groups to receive intraperitoneal injections with a single dose of STZ （40, 50, or 60 mg/kg）, 3 doses of 25 mg/kg STZ （given at the interval of 24 h）, or no treatment （blank control）. The dynamic change of blood glucose was observed within 72 h after the first injection. Blood glucose was then monitored every 3 days and the general conditions of the rats were recorded. In the 9th week, fasting blood samples were collected for biochemical analysis and the pancreas, kidney, liver, and eye were examined for pathologies. Results Within 72 h after STZ injection, blood glucose first slightly increased and then decreased and again increased to maintain a high level. Death occurred in rats receiving injections with 50 and 60 mg/kg STZ on the third day. In the surviving rats in the 4 STZ-injected groups, the success rate of modeling was 70%, 89%, 100%, and 100%, respectively. Blood glucose showed an inverse correlation with the body weight of the rats. Cataract was observed in the 10th week in rats injected with 40 mg/kg STZ and in the 8th week in the other groups. In the 9th week the rats receiving 40 mg/kg STZ showed normal insulin, C-peptide, urea, UA, Cr, ALT, AST, TP, and ALB levels, but the rats in the other groups all showed variations in these biochemical indices, which corresponded to the pathological findings in the pancreas, kidneys, and liver. Conclusions Three STZ doses of 25 mg/kg is optimal and efficient for inducing diabetes in rats with stable hyperglycemia. Both fasting and random blood glucose tests contribute to the evaluation of the complications of diabetes. The eyes are the most sensitive to hyperglycemia, followed by the kidneys and then by the liver.