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目的:探讨肾元颗粒对糖尿病小鼠肾脏中miR-199b-5p/Klotho/FGFR-1/EGR-1通路及钙磷代谢的影响。方法:链脲佐菌素(Streptozotocin,STZ)诱导小鼠糖尿病模型,模型成功后随机分为肾元颗粒组[4.55 g/(kg·d)]10只和模型对照组10只,另设空白对照组10只。给予相应药物灌胃8周,给药前后检测血糖以及血清中肌酐(SCr)、尿素氮(BUN)、钙(Ca)和磷(P),采用RT-q PCR检测肾脏组织中miR-199b-5p、Klotho、FGFR-1和EGR-1核糖核酸表达情况,采用western-blot(WB)法检测Klotho、FGFR-1和EGR-1蛋白表达情况,检测小鼠右下肢平均骨密度。结果:用药后与空白对照组相比,模型对照组P、SCr升高(P<0.05),Ca、骨密度明显降低(P<0.05),同时miR-199b-5p和EGR-1表达上调(P<0.05),Klotho和FGFR-1表达下调(P<0.05)。用药后与模型对照组比较,肾元颗粒组P、SCr降低(P<0.05),Ca升高(P<0.05),miR-199b-5p、EGR-1表达下调(P<0.05),Klotho、FGFR-1表达上调(P<0.05)。结论:肾元颗粒缓解糖尿病肾损害和改善钙磷代谢异常的作用机制,或与miR-199b-5p/Klotho/FGFR-1/EGR-1通路有关。
OBJECTIVE: To investigate the effect of Shenyuan granule on miR-199b-5p / Klotho / FGFR-1 / EGR-1 pathway and calcium and phosphorus metabolism in the kidney of diabetic mice. Methods: Diabetic mice were induced by streptozotocin (STZ). The rats were randomly divided into 10 groups (n = 10), which were treated with Shenyuan granule group [4.55 g / (kg · d) Control group of 10. The rats were given gavage for 8 weeks. Blood glucose, serum creatinine (SCr), blood urea nitrogen (BUN), calcium (Ca) and phosphorus (P) were measured before and after treatment. The expression of miR-199b- 5p, Klotho, FGFR-1 and EGR-1. The expression of Klotho, FGFR-1 and EGR-1 protein were detected by Western-blot (WB) Results: Compared with the blank control group, the levels of P and SCr in the model control group were significantly increased (P <0.05), the BM and BMD were significantly decreased (P <0.05), and the expression of miR-199b-5p and EGR- P <0.05). The expressions of Klotho and FGFR-1 were down-regulated (P <0.05). Compared with the model control group, the levels of P and SCr in Shenyuan granule group were significantly decreased (P <0.05), Ca was increased (P <0.05), the expression of miR-199b-5p and EGR- FGFR-1 expression was up-regulated (P <0.05). Conclusion: Shen Yuan Granule can relieve diabetic nephropathy and improve the mechanism of abnormal metabolism of calcium and phosphorus, or with miR-199b-5p / Klotho / FGFR-1 / EGR-1 pathway.