交感能受体阻断剂和去肾神经对5/6肾切除大鼠的肾脏保护作用

The Renoprotective Actions of Sympathetic Blocking Agent and Renal Denervation in the Rat Renal Ablation Model

目的探讨交感能受体阻断剂与去肾神经对慢性进行性肾小球硬化(5/6肾切除大鼠慢性肾衰竭动物模型)的肾脏保护作用。方法雌性Wistar大鼠40只,体质量为(200±10)g,随机分成4组,每组10只。阴性对照组行假手术(麻醉后行肾周包膜剥除术),术后2周开始灌服饮用水;阳性对照组行5/6肾切除术,术后2周灌服饮用水;交感阻断剂组行5/6肾切除术,术后2周灌服交感能受体阻断剂(阿尔玛尔20 mg.kg-.1d-1);去肾神经组行5/6肾切除术后2周行残肾去肾神经术(2周后开始灌服饮用水)。干预时间为8周。所有大鼠术后第2、4、6、8、10周用鼠尾测压仪测量大鼠血压并将大鼠置于代谢笼,留取24 h尿液,之后以考马斯亮蓝法行尿蛋白定量检测;术后10周即实验结束时采血测定血红蛋白及生化指标;同时留取肾脏标本行肾脏病理、免疫印迹测定Ⅲ型胶原(Col-Ⅲ)、Ⅳ型胶原(Col-Ⅳ)及血管紧张素Ⅱ1型受体(AT1-R),应用实时荧光定量PCR检测Col-Ⅲ、Col-Ⅳ及AT1-R的mRNA的表达。结果与阴性对照组相比,阳性对照组大鼠的血压[(173.49±16.48)mmHg vs(118.67±13.34)mmHg)]和尿蛋白定量[(35.35±4.58)mg/24 h vs(6.19±2.70)mg/24 h)]均明显升高(P<0.05),肾脏病理改变明显加重(P<0.05),Col-Ⅲ、Col-Ⅳ和AT1-R及其mRNA的表达均明显增多(P<0.05);与阳性对照组相比,交感阻断剂组和去肾神经组大鼠的血压改善[(107.99±12.35)mmHg,(115.67±15.53)mmHg vs(173.49±16.48)mmHg)],尿蛋白定量减少[(14.23±0.69)mg/24 h,(16.49±3.77)mg/24 h vs(35.35±4.58)mg/24 h)](P<0.05),病理改变减轻,Col-Ⅲ、Col-Ⅳ、AT1-R及其mRNA的表达有不同程度的改善,其中尤以AT1-R的蛋白定量及其mRNA的表达明显减少(P<0.05);但两个干预组不论是血压、尿蛋白定量、血红蛋白水平、生化指标、病理改变还是Col-Ⅲ、Col-Ⅳ、AT1-R水平以及其mRNA表达均无统计学差异(P>0.05)。结论交感能受体阻断剂和去肾神经均能够明显减轻和延缓5/6肾切除大鼠的肾小球纤维化、硬化,起到良好的肾脏保护作用。

Objective To disscuss the renoprotective actions of the sympathetic blocking agent and renal denervation in the rat renal ablation model.Methods 40 wistar rats were randomly devided into 4 groups.The first group served as negative control by sham operating.The second one as positive control by 5/6 subtotal nephrectomy（SNX）.The third one was underwent SNX,The fourth group underwent SNX and resection of dorsal roots,i.e.rhizotomy.The negative control,the positive control group and the fourth group were administrated tap water,the third group was given sympathetic blocking agent for 8 weeks.Results At the end of the study,the blood pressure of the rats was 118.67±13.34 mmHg in the negative control group,173.49±16.48 mmHg in the positive control group,115.67±15.53 mmHg in the third group and 107.99±12.35 mmHg in the fourth group,respectively.Albuminuria was 6.19±2.70,35.35±4.58,16.49±3.77,14.23±0.69 mg/24 h,respectively.The glomerulosclerosis of the third and fourth group were better than that of the others.The lowest indices for collagen Ⅲ,collagen Ⅳ and AT1-R were found in the third and fourth group（P〈0.05）.Conclusion The sympathetic blocking agent and renal denervation can protect the remanent kidney injury.