安博维对环孢素A慢性肾毒性大鼠肾间质骨桥蛋白表达及巨噬细胞浸润的影响  

Influnence of irbesartan on expression of opn and interstitial ED1+ macrophages infiltration in rats with chronic cyclosporine A nephrotoxicity

作　　者：白亚君[1] 景宇[1] 陶冶[1] 吴欣[1] 李聃丹[1] 刘其峰[1] 

机构地区：[1]四川大学华西医院肾脏内科,成都610041

出　　处：《国际泌尿系统杂志》2006年第6期721-724,共4页International Journal of Urology and Nephrology

摘　　要：目的①观察安博维(厄贝沙坦)干预治疗后环孢素A(CsA)所致慢性肾毒性大鼠肾脏病理变化。②观察安博维对CsA慢性肾毒性大鼠模型肾骨桥蛋白(OPN)表达及间质ED1阳性巨噬细胞浸润的影响,以探讨安博维防护CsA慢性肾毒性的可能机制。方法给进低盐饮食SD大鼠灌胃20mg·(kg·d)-1剂量的CsA制作大鼠CsA肾毒模型,同时以10mg·(kg·d)-1剂量的安博维胃饲以预防肾毒性。于用药后第1、2、4周末时分别处死各组大鼠,免疫组织化学法测定OPN、ED1的表达,用HE染色观察肾脏病理变化。结果安博维能明显改善CsA肾中毒大鼠的一般情况,减少肾小管上皮细胞空泡变性和萎缩,减少间质炎细胞浸润及间质纤维化。免疫组化结果显示模型组肾小管-间质OPN与ED1表达较对照组增加(p<0.05);在试验各时间点,安博维组大鼠肾小管-间质ED-1阳性巨噬细胞数量及OPN表达较模型组显著减少(p<0.05);OPN仍高于对照组((p<0.05),ED-1阳性巨噬细胞数量在第1、2周末与对照组无差异(p>0.05),但在第4周末高于对照组(p<0.05)。结论安博维能减轻CsA慢性肾毒性的肾脏病理损伤,这一防治作用可能与其减少ED-1阳性巨噬细胞浸润及下调OPN表达有关。Objectives To evaluate the effect of irbesartan on chronic cyclosporine A （ CsA ） nephrotoxicity and explore the mechanisms of protective effect of it. Methods Rats were on low salt diet and CsA was administered by gastric gavage at a dose of 20mg/kg once daily for 28 days to establish the cyclosporine A nephrotoxicity models, meanwhile irbesartan was given to these rats in experimental group in a dose of 10mg·（kg·d）^-1 by gastric garage. The renal morphology were observed at 1 st, 2nd and 4th week after administration of irbesartan. Results CsA induced the corruption of normal condition especially the weight lost were markedly delayed after administration of irbesartan. On histopathology irbesartan attenuated tubular cells vacuolations as well as interstitial damage including interstitial ED1 ＋ macrophages infiltration and focal interstitial fibrosis. Meanwhile, irbesartan down - regulated the protein of OPN in kidney. Conclusions Irbesartan could attenuate the structural changes of kidney in chronic CsA nephrotoxicity rats. Decreased CsA - related ED1 ＋ macrophages infiltration and up - regulated OPN expression in the kidney might be related to the mechanisms of protective effect of irbesartan to CsA induced chronic nephrotoxicity.

关 键 词：肾疾病 环孢菌素 蛋白质类 巨噬细胞 

分 类 号：R692[医药卫生—泌尿科学]