缬沙坦对肾小球硬化大鼠肾组织单核细胞趋化蛋白-1表达的影响

目的观察缬沙坦对肾小球硬化大鼠肾组织单核细胞趋化蛋白-1(MCP-1)表达的影响,探讨血管紧张素转化酶Ⅱl-型受体拮抗剂(AT1RA)对肾脏的保护作用。方法雄性SD大鼠36只随机分为对照组、肾小球硬化组和缬沙坦治疗组,每组12只。切除肾小球硬化组和缬沙坦治疗组大鼠左肾,1周后按5 mg.kg-1的剂量于尾静脉注射阿霉素,对照组行假手术及尾静脉注射等量生理盐水,注射阿霉素后次日始缬沙坦治疗组予缬沙坦20 mg.kg-1的剂量每日晨灌胃1次,对照组和肾小球硬化组仅灌以2 mL自来水。灌胃12周后处死大鼠,切取右肾用于肾脏病理分析,免疫组织化学法测定肾组织MCP-1。结果(1)形态学改变:对照组大鼠肾小管结构正常;肾小球硬化组多数肾小球呈节段性硬化,许多肾小球及肾小管受累;缬沙坦治疗组肾脏病变轻于肾小球硬化组,且肾小球硬化指数明显低于肾小球硬化组(P<0.01);(2)MCP-1的表达:对照组肾小管中有少量MCP-1的表达,在肾小球内几乎不表达,在肾小球硬化组和缬沙坦治疗组肾小球及肾小管内表达皆强于正常对照组(P<0.01)。缬沙坦治疗组MCP-1表达较肾小球硬化组弱(P<0.01)。结论缬沙坦可能通过阻断肾小球硬化大鼠肾素-血管紧张素系统,降低MCP-1在肾脏中的表达,抑制或减轻了巨噬细胞浸润,进而延缓肾小球硬化的进展。

Influence of valsartan on the expression of monocyte chemoattractant protein-1 in nephridial tissue of glomerular sclerosis rats

Objective To observe the Influence of valsartan on the expression of monocyte chemoattractant protein-1(MCP-1) in nephridial tissue of glomerular sclerosis rats,and to study the protection of angiotensin-converting enzyme Ⅱtype-1 receptor antagonist(AT1RA) on kidney.Methods Thirty-six male Sprague-Dawley rats were randomly divided into three groups: control group,glomerular sclerosis(GS) group and valsartan group,twelve rats in each group.The left kidney of rats in GS group and valsartan group were uninephrectomized and injected with adriamycin(5 mg·kg-1) through tail vein one week later,next day,the rats in valsartan group were treated with valsartan(20mg·kg-1·d-1) by intragastric administration everyday for twelve weeks.The rats in control group were dealt with sham operation,and were given normal sodium.All rats were killed twelve weeks later,the right kidneies were used for observing pathological change,and the expression of MCP-1 in nephridial tissue were detected by immunohistochemical method.Results(1)Change of morphology:the structure of renal tubule was normal in control group,most glomcruluses were segmented sclerosis in GS group,the renal lesions in valsartan group was minorer than this in GS group.Glomerulosclerosis index in GS group and valsartan group was higher than this in control group(P<0.01),and the glomerulosclerosis index in valsartan group was lower than this in GS group(P<0.01).(2)Expression of MCP-1:the expression of MCP-1 in glomerulus and renal tubule of GS group and valsartan group was higher than this in control group(P<0.01),the expression of MCP-1 in valsartan group was weaker than this in GS group(P<0.01).Conclusion Valsartan may delay the progression of GS by interrupting the renin-angiotensin system of glomerular sclerosis rats,degrading the expression of MCP-1 in kidney,and inhibiting macrophage infiltrating.