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目的观察肾衰Ⅱ号方对5/6(ablation/infarction,A/I)肾切除慢性肾功能衰竭(chronic renal failure,CRF)大鼠残余肾组织纤维化及血管紧张素Ⅱ(AngⅡ)和神经型一氧化氮合酶(nNOS)表达的影响,并初步探讨其作用机制。方法选取57只SD雄性大鼠按5/6(A/I)肾衰模型法制备大鼠模型。造模后随机分为模型组、肾衰Ⅱ号方组(中药组,肾衰Ⅱ号方浓煎液2mL灌胃)和西药组(氯沙坦钾合福辛普利钠混悬液,2mL灌胃),每组15只,另选取15只大鼠作为正常组,正常组和模型组予等量纯净水灌胃,各组均每天干预1次,连续干预60天。检测各组大鼠SCr、BUN、内生肌酐清除率(creatinine clearance rate,CCr),采用Western blot法测定大鼠残余肾皮质、髓质AngⅡ和nNOS蛋白表达,观察肾组织病理形态。结果与正常组比较,模型组SCr、BUN升高,CCr降低(P<0.01),提示造模成功。与本组干预前比较,中药组及西药组SCr、BUN水平下降,CCr水平升高(P<0.01)。与模型组比较,中药组及西药组SCr、BUN水平及髓质AngⅡ表达均降低(P<0.01,P<0.05),CCr水平及皮质、髓质nNOS表达明显升高(P<0.01,P<0.05)。肾组织病理显示,中药组病理变化明显减轻,优于模型组。结论肾衰Ⅱ号方可以改善5/6肾切除CRF大鼠的肾功能,减轻肾间质纤维化,其作用机制可能与调节肾内失衡的AngⅡ和nNOS信号转导途径有关。
Objective To observe the effect of Shenshuai Decoction Ⅱ on the remnant renal fibrosis and the changes of angiotensin Ⅱ (AngⅡ) and nerve in 5/6 (ablation / infarction, A / I) nephrectomy rats with chronic renal failure (CRF) Type nitric oxide synthase (nNOS) expression, and to explore its mechanism of action. Methods Fifty-seven male Sprague-Dawley rats were randomly divided into five groups according to 5/6 (A / I) renal failure model. After modeling, the rats were randomly divided into model group, Renxin DecoctionⅡgroup (Chinese medicine group, Ren Shen Decoction Ⅱ decoction 2mL intragastric administration) and western medicine group (losartan potassium combined with fosinopril sodium suspension, 2mL 15 rats in each group, 15 rats in the other group were selected as the normal group. The rats in the normal group and model group were treated with the same amount of pure water. The rats in each group were treated once daily for 60 days. The levels of SCr, BUN and creatinine clearance rate (CCr) in rats were measured. The expressions of Ang Ⅱ and nNOS in renal cortex and medulla were determined by Western blot. The pathological changes of kidney were observed. Results Compared with the normal group, SCr and BUN in the model group increased and CCr decreased (P <0.01), suggesting successful modeling. Compared with the pre-intervention group, the levels of SCr and BUN in Chinese medicine group and western medicine group decreased and CCr level increased (P <0.01). Compared with model group, the levels of SCr, BUN and medulla Ang Ⅱ in Chinese medicine group and western medicine group were significantly decreased (P <0.01, P <0.05), and CCr level and nNOS expression in cortex and medulla were significantly increased (P <0.01, P < 0.05). Kidney histopathology showed that the pathological changes of TCM group were significantly alleviated, which was better than the model group. Conclusion Ren Shen Decoction Ⅱ can improve renal function and reduce renal interstitial fibrosis in 5/6 nephrectomized CRF rats, and its mechanism may be related to Ang Ⅱ and nNOS signal transduction pathways that regulate intrarenal imbalance.