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目的:探讨缓慢注入肾上腺髓质素(AM)对高血压引起的肾衰竭大鼠的肾脏保护作用及其机制。方法:Dahl盐敏感(DS)大鼠18只和盐抵抗(DR组)大鼠9只从6周龄开始喂以高盐饮食形成肾衰竭模型。11周龄时将DS大鼠分为2组:DS-AM组(9只)注入重组人AM,DS组(9只)注入0.9%氯化钠溶液,均7周。结果:7周后,DS组及DS-AM组大鼠表现为肾功能减退、形态异常、激素水平升高。但与DS组比较,DS-AM组大鼠的肾功能以及组织学表现可显著改善,并抑制血浆肾素浓度及醛固酮水平的增加(P<0.01),而平均动脉压没有改变,DR组、DS组、DS-AM组大鼠的肾小球损伤分数分别为13.13、95.65、47.82,两两比较均差异有统计学意义(P<0.01或P<0.05)。结论:增加内源性AM对慢性高血压性肾衰竭起代偿作用,长期注入AM在该高血压模型中可部分通过抑制循环及肾素-血管紧张素系统而发挥肾脏保护作用。
Objective: To investigate the renal protective effect of chronic injection of adrenomedullin (AM) on renal failure rats induced by hypertension and its mechanism. Methods: Eighteen Dahl salt-sensitive rats and nine rats of salt-resistant (DR) rats were fed a high-salt diet from the age of 6 weeks to form a model of renal failure. At 11 weeks of age, DS rats were divided into two groups: DS-AM group (n = 9) injected with recombinant human AM, and DS group (n = 9) injected 0.9% sodium chloride solution for 7 weeks. Results: After 7 weeks, rats in DS group and DS-AM group showed renal dysfunction, abnormal morphology and increased hormone levels. However, compared with DS group, the renal function and histological appearance of rats in DS-AM group were significantly improved and the plasma renin concentration and aldosterone level were increased (P <0.01), while the mean arterial pressure was not changed. In DR group, The scores of glomerular injury in DS group and DS-AM group were 13.13, 95.65 and 47.82, respectively, with significant difference (P <0.01 or P <0.05). CONCLUSIONS: Increased endogenous AM plays a compensatory role in chronic hypertensive renal failure. Long-term AM injection exerts renal protective effects in part by inhibiting circulatory and renin-angiotensin system in this hypertensive model.