他克莫司对糖尿病大鼠肾组织巨噬细胞浸润、增殖及活化的影响

目的探讨他克莫司对糖尿病大鼠肾脏保护作用的机制与肾脏内巨噬细胞浸润、增殖及活化的关系。方法应用链脲佐菌素建立大鼠糖尿病模型，随机分为对照组、模型组、他克莫司0．5及1．0mg-1·kg-1·d-1给药组（模型组＋他克莫司0．5、1．0），4周后观察大鼠相对。肾质量、尿白蛋白排泄率，应用免疫组化方法，检测肾组织巨噬细胞表面标志、增殖细胞核抗原及诱生性一氧化氮合酶的表达。结果模型组＋他克莫司0．5、1．0组大鼠尿白蛋白排泄率水平明显低于模型组。免疫组化显示模型组大鼠肾组织巨噬细胞表面标志阳性、巨噬细胞表面标志阳性增殖细胞核抗原阳性及巨噬细胞表面标志阳性诱生性一氧化氮合酶细胞数阳性明显高于对照组，模型组＋他克莫司0．5、1．0组巨噬细胞表面标志阳性细胞数与模型组比较无明显差异，巨噬细胞表面标志阳性增殖细胞核抗原阳性及巨噬细胞表面标志阳性诱生性一氧化氮合酶细胞数明显低于模型组。结论他克莫司肾脏保护作用的机制可能部分与抑制肾组织中巨噬细胞增殖及活化有关。

Effect of tacrolimus on macrophage accumulation,proliferation and activation in the kidney of early diabetic rats

Objective To investigate the effect of Tacrolimus on macrophage accumulation, proliferation and activation in the kidney of early diabetic rats. Methods Rat diabetic mellitus models were induced with streptozotoein. Tacrolimus（0. 5 or 1.0 mg/kg）was orally administered once a day for 4 weeks. Relative kidney weight and 24-h urinary albumin excretion rate（AER） were measured. ED-1, proliferating cell nuclear antigen （PCNA） and inducible nitric oxide synthase （iNOS） positive macro- phages were examined by using immunohistochemistry and double immunohistochemistry. Results El- evated AER was markedly attenuated by Taerolirnus treatment with 0.5 and 1.0 mg-1. kg-1. day -1. There were marked accumulation of ED-1 ＋ cells in diabetic kidney, which were not inhibited by treat- ment with Tacrolimus treatment with 0.5 and 1.0 mg-1. kg-1. day -1. ED-1＋ PCNA＋ cells and ED-1 ＋ iNOS＋ cells were significantly elevated in kidneys from diabetic group,while they were significantly inhibited by Tacrolimus treatment with 0.5 and 1.0 mg-1. kg-1. day -1. Conclusions Taerolimus could ameliorate early renal injury and its mechanism may be at least partly correlated with the suppression of increased macrophages activation.