健脾益肾、祛瘀化浊法对糖尿病肾病大鼠肾脏保护作用的研究

Study on the Protective Effect of Spleen-invigorating and Kidney-nourishing and Blood Stasis-eliminating and Turbid Substance-removing Method on Kidney in Diabetic Nephropathy Rats

目的探讨健脾益肾、祛瘀化浊法对糖尿病肾病(DN)大鼠肾脏的保护作用及机制。方法链脲佐菌素(STZ)诱导糖尿病肾病大鼠模型,随机分为降糖精低剂量组、降糖精中剂量组、降糖精高剂量组,ACEI组(阳性对照治疗组)各16只,另以16只正常大鼠作为正常组。降糖精颗粒低、中、高剂量组分别灌胃给予降糖精颗粒9 g(生药量)/kg,18 g(生药量)/kg和36 g(生药量)/kg,1次/天; ACEI组给予贝那普利(1 mg/kg·d-1)灌胃,糖尿病肾病模型组及正常组给予0. 9%Na Cl溶液灌胃。共观察8周,检测各组8周末24h尿微量白蛋白定量、肾重/体重、肾功能(Scr、BUN),免疫组织学检测。结果与正常对照组比较,模型组大鼠血糖明显升高(P <0. 05),体质量明显下降(P <0. 05),肾质量、肾质量/体质量明显增加(P <0. 05);与模型组比较,降糖精各剂量组及ACEI组大鼠空腹血糖明显降低(P <0. 05),体质量明显高增加(P <0. 05),肾质量、肾质量/体质量明显降低(P <0. 05)。降糖精各剂量组及ACEI组之间差异不明显(P> 0. 05)。与正常对照组比较,模型组大鼠UAER、BUN和Scr水平均明显增高,差异有统计学意义(P <0. 05);与模型组比较,降糖精各剂量组及ACEI组大鼠UAER、BUN和Scr水平均显著下降,差异有统计学意义(P <0. 05)。降糖精各剂量组及ACEI组之间差异不明显(P> 0. 05)。由Western blot结果看出,模型组大鼠肾组织CTGF和VEGF含量高于正常组;降糖精各剂量组及ACEI组大鼠肾组织CTGF和VEGF含量均低于模型组;降糖精剂量升高,CTGF和VEGF表达降低。结论健脾益肾、祛瘀化浊法能明显改善大鼠肾脏功能,其机制可能与抑制CTGF、VEGF的表达有关。

Objective： To study the protective effect and mechanism of spleen-invigorating and kidney-nourishing and blood stasis-eliminating and turbid substance-removing method on kidney in diabetic nephropathy （DN） rats. Methods： Rat models of diabetic nephropathy induced by streptozotocin （STZ） were randomly divided into low, medium and high dose groups of Jiangtangjing granules, and ACEI group （positive control group）, 16 rats per group. Another 16 normal rats were used as the normal group. The low, medium and high doses of Jiangtangjing granule groups were administered intragastrically with granules 9 g （raw dose）/kg, 18 g （raw dose）/kg and 36g （raw dose）/kg, once a day. The ACEI group was administered with benazepril （1 mg/kg·d -1 ）, and the diabetic nephropathy model group and the normal group were administered with 0.9% NaCl solution. The observation lasted 8 weeks. The 24-hour urine microalbumin quantitation, kidney weight/body weight, renal function （Scr, BUN） of each group were detected by immunohistochemistry at the end of the 8th week. Results： Compared with that of the normal control group, the blood glucose of the model group significantly increased （ P 〈0.05）, the body weight significantly decreased （ P 〈0.05）, and the kidney mass and kidney mass/body mass significantly increased （ P 〈0.05）. Compared with that of the model group, the fasting blood glucose of various dose groups and the ACEI group decreased significantly （ P 〈0.05）, the body weight increased significantly （ P 〈0.05）, and the kidney mass and kidney mass/body mass decreased significantly （ P 〈0.05）. There was no significant difference between the various dose groups of Jiangtangjing and the ACEI group （ P 〉0.05）. Compared with that of the normal control group, the levels of UAER, BUN and Scr of the model group significantly increased, and the difference was statistically significant （ P 〈0.05）. Compared with that of the model group, the level of UAER, BUN and Scr of the various dose groups and the ACEI group decreased significantly, and the difference was statistically significant （ P 〈0.05）. There was no significant difference between the various dose groups and the ACEI group （ P 〉0.05）. The results of Western blot showed that the levels of CTGF and VEGF in the renal tissue of the model group were higher than those in the normal group. The contents of CTGF and VEGF in the renal tissue of the Jiangtangjing groups and the ACEI group were lower than those in the model group. With the increase of Jiangtangjing doses, the expression of CTGF and VEGF deceased. Conclusion： The spleen-invigorating and kidney-nourishing and blood stasis-eliminating and turbid substance-removing method can improve the kidney function of rats, and its mechanism may be related to the inhibition of CTGF and VEGF expression.