骨化三醇对SD大鼠经链脲佐菌素诱导糖尿病发生过程的影响

The effects of 1,25-dihydroxyvitamin D3 on streptozotocin-induced diabetes in rats

目的探讨骨化三醇[1,25(OH)2D3]对链脲佐菌素(streptozocin,STZ)所致SD大鼠糖尿病发生过程的影响,为人类1型糖尿病的预防提供实验依据。方法将28只雄性SD大鼠随机分为3组。20只大鼠采用STZ造成糖尿病模型,其中1,25(OH)2D3组(n=10)造模前4周接受1,25(OH)2D31μg/(kg·d)溶于0.05 ml花生油灌胃,STZ对照组(n=10)造模前4周采用花生油灌胃,0.05ml/d。STZ对照组和1,25(OH)2D3组均于实验第5周开始第1天腹腔注射福氏完全佐剂(CFA),0.5 ml/只,第2天按30 mg/kg STZ枸椽酸溶液腹腔注射,以STZ对照组全部成模为准,停止造模;成模后2周处死。其余8只为正常对照组,采用花生油灌胃,0.05ml/d,灌胃4周,不注射STZ。观察1,25(OH)2D3对STZ所致SD大鼠糖尿病发病情况及对胰岛素、血糖的影响。结果 STZ对照组10只大鼠全部造模成功,1,25(OH)2D3组10只大鼠中6只成模,造模成功率差异有统计学意义(P<0.05)。1,25(OH)2D3组血糖曲线下面积(AUC)为(21.301±4.699)mmol·h/L,明显低于STZ对照组[(31.183±4.567)mmol·h/L],差异有统计学意义(P<0.05)。1,25(OH)2D3组胰岛素AUC为(1.105±0.356)μg·h/L,明显高于STZ对照组[(0.472±0.162)μg·h/L],差异有统计学意义(P<0.05)。血清1,25(OH)2D3水平与胰岛素AUC呈正相关,而与血糖AUC呈负相关,有统计学意义(r=0.517,P=0.04;r=-0.562,P=0.02)。结论 1,25(OH)2D3对STZ所致SD大鼠糖尿病的发生有一定的预防作用。

Objective To study the prophylactic effects of 1,25-dihydroxyvitamin D3 on the diabetes induced by streptozotocin（STZ） in Sprague-Dawley rats and to provide the basis for prevention of human type 1 diabetes. Methods Twenty eight male Sprague Dawley rats were divided into three groups： 10 rats orally administered with 1,25-dihydroxyvitamin D3 [1 μg/（kg·d）,dissolved in 0.05 ml peanut oil] for 4 weeks then intraperitoneally injected by 30 mg/kg STZ,10 rats orally administered with 0.05 ml peanut oil for 4 weeks then intraperitoneally injected by 30 mg/kg STZ,8 rats only orally administered with 0.05 ml peanut oil for 4 weeks. All rats were executed in 2 weeks after the diabetes model in STZ group was established. The incidence of diabetes was observed,and the plasma glucose and insulin were measured to observe AUC. Results In STZ group the incidence of diabetes was10/10,in 1,25-dihydroxyvitamin D3 group the incidence of diabetes was 6/10. There was significant difference of diabetes incidence between two groups（P〈0.05）. The glucose AUC [（21.301±4.699） mmol·h/L] in 1,25-dihydroxyvitamin D3 group was significantly lower than that [（31.183±4.567） mmol·h/L] in STZ group（P〈0.05）. The insulin AUC [（1.105±0.356） μg·h/L] in 1,25-dihydroxyvitamin D3 group was significantly higher than that [（0.472±0.162） μg·h/L] in STZ group（P〈0.05）. The serum level of 1,25-dihydroxyvitamin D3 was correlated positively with insulin AUC,but was correlated negatively with glucose AUC（r =0.517,P =0.04;r =-0.562,P =0.02）. Conclusion 1,25-dihydroxyvitamin D3 may have the preventive effect on diabetes induced by streptozotocin in Sprague-Dawley rats to some extent.