六味地黄汤合黄连解毒汤对糖尿病肾病大鼠的肾脏保护作用及相关机制
Protective Effect and Mechanism of Liuwei Dihuang Combined with Huanglian Jiedu Decoction on Diabetic Nephropathy Rats
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摘要: 目的 观察六味地黄汤合黄连解毒汤对糖尿病肾病大鼠血清肿瘤坏死因子(TNF-α)、白介素-17(IL-17)、血管内皮生长因子(VEGF)、C反应蛋白(CRP)表达的影响,探讨其对糖尿病肾病大鼠的肾脏保护作用及其机制。方法 SD雄性大鼠60只,随机选取10只作为正常对照组,余下的50只采用链脲佐菌素腹腔注射(35 mg/kg)+高热量饮食喂养方法制作糖尿病肾病大鼠模型,造模成功后随机分为模型组、六味地黄汤合黄连解毒汤组、罗格列酮组,分别灌胃给药12周,比较各组大鼠空腹血糖(FBG)、血甘油三酯(TG)、总胆固醇(TC)、空腹胰岛素(FINS)、血肌酐(Scr)、尿素氮(BUN)、尿蛋白/尿肌酐的水平,测定血清CRP、TNF-α、IL-17、VEGF含量,观察肾脏病理变化。结果 与糖尿病肾病模型组比较,六味地黄汤合黄连解毒汤组的FBG、TG、TC、Scr、BUN、尿蛋白水平均明显降低(P<0.05),血清TNF-α、IL-17、VEGF、CRP含量下降(P<0.05),肾组织病理损伤明显减轻(P<0.05)。结论 六味地黄汤合黄连解毒汤能够减少蛋白尿,改善肾功能,减轻肾脏病理损害,其作用机制可能与其降低糖尿病肾病大鼠血清炎性因子TNF-α、IL-17、VEGF、CRP表达有关。Abstract: OBJECTIVE To observe the effect of Liuwei Dihuang combined with Huanglian Jiedu Decoction on the expression of serum tumor necrosis factor-α (TNF-α), interleukin-17 (IL-17), vascular endothelial growth factor (VEGF) and C reactive protein (CRP) in diabetic nephropathy rats, and to investigate the protective effect on renal function and its mechanism. METHODS 10 SD rats were randomly picked to form normal control group and the left 50 rats were induced into diabetic nephropathy model by intraperitoneal injection of streptozotocin (35 mg/kg) and fed with high calorie forage, then randomly divided into 3 groups: model group, Liuwei Dihuang combined with Huanglian Jiedu Decoction group, and rosiglitazone group. The effects of Liuwei Dihuang combined with Huanglian Jiedu Decoction on serum levels of glucose, insulin, triglyceride, total cholesterol, creatinine, blood urea nitrogen (BUN), CRP and urinary protein were observed. The expression of the serum TNF-α, IL-17 and VEGF were examined and the kidneys were determined to observe the renal pathological changes. RESULTS Compared with the model group, levels of serum glucose, insulin, triglyceride, total cholesterol, creatinine, BUN, CRP and urinary protein in the Liuwei Dihuang combined with Huanglian Jiedu Decoction group significantly decreased; the serum TNF-α, IL-17 and VEGF levels also decreased, while the kidney organization pathology damage was reduced obviously. CONCLUSION The treatment for diabetic nephropathy rats with Liuwei Dihuang combined with Huanglian Jiedu Decoction could lead to the decrement of urinary protein, improvement of renal function and reduction of renal pathology damage, and the mechanism might related to its action in inhibition extra expression of TNF-α, IL-17, VEGF, CRP in diabetic nephropathy rats.