洛沙坦对糖尿病大鼠肾脏炎症反应及足细胞损伤的影响

目的 探讨洛沙坦对糖尿病大鼠模型肾组织炎症反应及足细胞损伤的影响。方法 Wistar大鼠随机分为3组：对照组（NC）、糖尿病组（DM）、洛沙坦治疗组（DL）。链脲菌素（STZ）注射建立糖尿病动物模型，洛沙坦治疗组在大鼠建立糖尿病同时即开始以洛沙坦（20mg·kg·d^-1）灌胃治疗。分别于2周和12周杀鼠，观察体重、肾重、肾重／体重指数、尿蛋白量（24h）、Scr、Ccr以及肾组织病理改变；免疫组化染色观察肾小球细胞间黏附分子（ICAM-1）、白细胞共同抗原（CD45）、nephrin、血管内皮生长因子（VEGF）表达的改变；免疫印迹观察肾组织nephrin、VEGF表达的改变。结果 （1）DL组大鼠肾重／体重指数、尿蛋白量（24h）、Ccr则均低于DM组，差异均有统计学意义（P均〈0．05），其病理改变程度也比DM组轻。（2）免疫组化及免疫印迹显示，DM组和DL组肾小球ICAM-1、CD45、VEGF表达均高于对照组，而DL组ICAM-1、CD45、VEGF表达均低于DM组；DM组和DL组大鼠肾小球nephrin表达低于对照组；DL组肾小球nephrin表达高于DM组，差异均有统计学意义（P均〈0．01）。结论 洛沙坦可能通过抑制肾组织白细胞浸润、炎症反应及减轻足细胞损伤，达到肾脏保护作用。

Effects of losartan on renal inflammation reaction and podocyte injury in the kidney of diabetic rat

Objective To investigate the effects of losartan on renal inflammation reaction and podocyte injury in the kidney of diabetic rat. Methods Wistar rats were randomly divided into normal control group (NC), diabetes group（DM）, and losartan treated group(DL)（20 mg·kg-1·d-1 by gavages）. Diabetes was induced by intraperitoneal injection of streptozotocin （STZ）. After administration of losartan for 2 weeks and 12 weeks, 24-hour urinary protein excretion (24 hUPE), Scr and Ccr were measured, and renal morphology was observed. The expression levels of ICAM-1, CD45, nephrin and VEGF were examined by immunohistochemistry and Western blot. Results Compared with DM, kidney weight （KW）, KW/body weight（KW/BW）, 24 hUPE and Ccr in DL were significantly decreased（P < 0.05，or P < 0.01）. The expression levels of ICAM-1, CD45 and VEGF in DM and DL group were higher than those in NC group. Losartan inhibited the increased levels of ICAM-1,CD45 and VEGF as well as decreased levels of nephrin in DL. The levels of ICAM-1, CD45, VEGF, nephrin and blood glucose were correlated with the excretion of urine protein. There was a positive correlation between ICAM-1 and VEGF (r = 0.756, P < 0.01), as well as CD45 and VEGF (r =0.774, P < 0.01). There was a negative correlation between ICAM-1 and nephrin (r =-0.589, P < 0.05), as well as CD45 and nephrin (r = -0.664, P < 0.01). Conclusion Renoprotection of losartan on diabetic rats may be mediated through, at least partly, suppressing the increase of renal inflammatory stress and attenuating podocyte injury.