目的:探讨活性维生素D3对2型糖尿病大鼠肾脏的保护作用及机制。方法:将40只SD雄性大鼠分为对照组(n=8)、模型组(n=8)、维生素D3高(n=8)、低剂量(n=8)组和阿卡波糖阳性对照组(n=8),给药6周后处死大鼠,测定大鼠血清肌酐(Scr)和尿素氮(BUN)水平;测定肾组织肾脏超氧化物歧化酶(SOD)、过氧化氢酶(CAT)、总一氧化氮合酶(tNOS)、过氧化氢(H2O2)的水平;采用Western blot检测肾组织PI3K/Akt通路相关蛋白表达水平。结果:与正常组相比,模型组大鼠血清Scr和BUN含量明显升高(P＜0.05);与模型组相比,维生素D3各剂量组大鼠血清Scr和BUN含量显著降低(P＜0.05)。与正常组相比,模型组大鼠肾组织H2O2、tNOS含量明显升高,而SOD、CAT水平显著降低(P＜0.05);与模型组相比,维生素D3各剂量组能抑制肾组织H2O2、tNOS的产生,同时显著升高肾组织SOD、CAT含量(P＜0.05)。与正常组相比,模型组p-PI3K/PI3K,p-Akt/Akt比值显著升高;与模型组相比,维生素D3各剂量组大鼠p-PI3K/PI3K,p-Akt/Akt比值显著降低(P＜0.05)。结论:活性维生素D3对2型糖尿病大鼠肾脏损伤具有保护作用,其机制可能与活性维生素D3介导PI3K/Akt信号通路调节氧化应激有关。
Objective: To investigate the protective effect and possible mechanisms of 1, 25-dihydroxy vitamin D3 on kidney in rats with type 2 diabetes mellitus. Methods: Sprague-Dawley male rats(n=40)were used in this experiments. All rats were randomly divided into the control group(n=8),model group(n=8), low-dose vitamin D3 group(n=8),high-dose vitamin D3 group(n=8), acarbose treatment group(n=8). Intragastric administration were continuously performed on all rats for 6 weeks and then were killed. The serum creatinine (Scr) and urea nitrogen (BUN) levels of rats were measured. The levels of superoxide dismutase (SOD), catalase (CAT), total nitric oxide synthase (tNOS) and hydrogen peroxide (H2O2) of renal tissues were detected. The expression of PI3K/Akt pathway related proteins in renal tissues was detected using Western blot. Results: Compared with the normal group, the contents of serum Scr and BUN in model group were significantly increased (P＜0.05). The contents of serum Scr and BUN of rats in groups with different doses of vitamin D3 decreased significantly comparing with the model group (P＜0.05). The contents of H2O2 and tNOS in renal tissue in the model group increased significantly, while the levels of SOD and CAT decreased significantly comparing with the normal group (P＜0.05). Compared with the model group, all the vitamin D3 groups could inhibit the production of H2O2 and tNOS and significantly increase the content of SOD and CAT in renal tissue (P＜0.05). Compared with the normal group, thep-PI3K/PI3K and p-Akt/Akt ration in the model group increased significantly (P＜0.05), but decreased significantly in vitamin D3 groups (P＜0.05). Conclusion: 1, 25-dihydroxy vitamin D3 has protective effect on kidney injury in type 2 diabetes rats, and the mechanism may be related to the regulation of oxidative stress through mediating PI3K / Akt signaling pathway.
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