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目的探讨血管紧张素Ⅱ受体阻断剂洛沙坦对系膜增殖型肾炎家兔系膜细胞增殖、系膜基质增多的的药效和作用特点。方法将雄性日本大耳白兔30只随机分成正常对照组、病理模型对照组和洛沙坦治疗组。建立家兔系膜增殖型肾炎模型。双缩脲法测定洛沙坦对系膜增殖型肾炎家兔24h尿蛋白排泄量;放免法测定血浆中内皮素及降钙基因相关肽的水平;自动图像分析仪测定各组肾小球的定量指数,系膜基质指数;用免疫组化法观察肾组织增殖性细胞核抗原(PCNA)表达。结果与病理模型对照组相比,洛沙坦治疗组家兔24h尿蛋白排泄量明显下降(P<0.05),系膜面积显著减少(P<0.05),内皮素(ET-1)降低、降钙素基因相关肽(CGRP)升高(P<0.05),PCNA阳性细胞数减少(P<0.05)。结论洛沙坦具有调节内皮素与降钙素基因相关肽病理性改变,减少系膜基质的增多,及系膜细胞的增殖,从而对肾炎家兔有明显的保护作用。
Objective To investigate the efficacy and role of losartan, an angiotensin Ⅱ receptor blocker, on mesangial cell proliferation and mesangial matrix in rabbits with mesangial proliferative glomerulonephritis. Methods Thirty male Japanese white rabbits were randomly divided into normal control group, pathological model control group and losartan treatment group. Rabbit mesangial proliferative nephritis model was established. Determination of urinary albumin excretion of losartan on mesangial proliferative nephritis rabbit by biuret method; Determination of endothelin and calcitonin gene-related peptide in plasma by radioimmunoassay; Quantitative analysis of glomeruli in each group by automatic image analyzer Index and mesangial matrix index. The expression of proliferating cell nuclear antigen (PCNA) in renal tissue was observed by immunohistochemistry. Results Compared with the control group, the urinary protein excretion of 24h in losartan group was significantly decreased (P <0.05), the mesangial area was significantly decreased (P <0.05), the ET-1 level was decreased Calcitonin gene related peptide (CGRP) increased (P <0.05), PCNA positive cells decreased (P <0.05). Conclusion Losartan can regulate the pathological changes of endothelin and calcitonin gene-related peptide, reduce the increase of mesangial matrix, and the proliferation of mesangial cells, which have a significant protective effect on nephritis rabbits.