辛伐他汀通过上调血红素氧合酶-1减少肾脏缺血再灌注损伤

目的:探讨辛伐他汀对肾缺血再灌注损伤(IRI)的影响及其作用机制。方法:30只雄性SD大鼠分成3组,治疗组术前连续3 d给予辛伐他汀10 mg·kg-1·d-1 ig,模型组和假手术组术前3 d生理盐水ig。治疗组与模型组大鼠左肾肾蒂夹闭45 min以诱导缺血再灌注损伤,并将右肾切除。假手术组仅行右肾切除术。术前和术后24 h取血;术后24 h处死大鼠,检测血清肌酐水平,了解肾脏功能及受损情况,观察肾组织病理改变,运用蛋白免疫印迹方法检测血红素氧合酶-1(HO-1)的表达水平,运用免疫组化方法对HO-1和ED-1阳性巨噬细胞进行定位。结果:治疗组和模型组相比,血清肌酐水平、肾损伤明显降低(P<0.05),肾组织中HO-1表达明显增加(P<0.05),表达HO-1的大部来自浸润的单核/巨噬细胞。结论:辛伐他汀能正向调节肾组织中HO-1的表达,从而发挥其抗炎作用,减轻肾组织损伤。

Simvastatin Reduce Renal Ischemia-reperfusion Injury byUp-Regulation of Heme Oxygenase-1

Objective: In the present study we addressed the ability and the mechanism of simvastatin to reduce ischemia-reperfusion injury (IRI) through up-regulation of heme oxygenase-1 (HO-1) expression. Method: Thirty male SD rats were divided into three groups. Rats in treatment group were given Simvastatin (10 mg ·kg^-1 ·d^-1)ig 3 days before operation;rats in the control group were given only saline pre-operatively. We induced IRI in these two groups by left renal pedicle clamping for 45 min and performed right kidney resection. Rats in the sham operation group only received right kidney resection. All the animals were sacrificed 24 h after IRI. Blood samples were drawn before the surgery and 24 h after IRI for renal function measurement. Renal morphology and expression of ED-1 and HO-1 were investigated by histological means,immunohistochemistry and Western blot,respectively. Result: Simvastatin pre-treatment reduced quantitative renal damage and attenuated renal dysfunction. Simvastatin treatment increased HO-1 expression on the protein level in the kidney. By immunohistochemistry we identified infiltrating macrophages as the major source for HO-1 expression at 24 h post-ischemia. Conclusion: Simvastatin treatment up-regulates HO-1 in circulating monocytes. The local delivery of HO-1 by infiltrating monocytes/macrophages exerts local anti-inflammatory effects after IRI and thus might reduce tissue destruction.