Statin pleiotropy against renal injury.
Statin pleiotropy against renal injury.
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DOI：
10.1111/j.1559-4572.2008.00052.x
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发表时间：
2009-01-01
期刊：
影响因子：
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通讯作者：
Elisaf, Moses S
中科院分区：
文献类型：
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作者：
Kostapanos, Michael S;Liberopoulos, Evangelos N;Elisaf, Moses S
他汀类药物可能表现出显着的肾脏保护作用超出其降脂能力。在此，作者回顾了来自人类和动物肾脏疾病模型的数据，以及他汀类药物对体外培养肾细胞的肾脏保护作用的研究。他汀类药物在慢性或急性肾功能损害的实验状态下可能对肾损伤产生非脂质依赖性益处。这些包括糖尿病和高血压肾小球硬化、自身免疫性肾小球肾炎、缺血/再灌注诱导的肾损伤和单侧输尿管梗阻性肾病。此外，他汀类药物通过减少甲羟戊酸产物的合成，抑制Rho和Ras鸟苷三磷酸酶的活化，这可能影响涉及肾脏炎症、纤维化、增殖和细胞死亡反应的各种信号传导途径。因此，他汀类药物在肾组织中发挥抗炎作用，防止肾瘢痕形成，并减少系膜或其他肾细胞型增殖，同时促进系膜细胞凋亡。他汀类药物治疗后，肾脏抗氧化作用以及随之而来的肾血管内皮功能调节也可能导致对肾损伤的多效性保护。
Statins may exhibit significant renoprotective effects beyond their lipid-lowering capacity. Herein, the authors review data from human and animal models of renal disease as well as from studies in cultured renal cells with regard to extralipid renoprotective properties of statins. Statins may exert lipid-independent benefits against renal injury in experimental states of chronic or acute renal function impairment. These include diabetic and hypertensive glomerulosclerosis, autoimmune glomerulonephritis, ischemia/reperfusion-induced renal damage, and unilateral ureteral obstructive nephropathy. Also, statins, by reducing the synthesis of mevalonate products, inhibit the activation of Rho and Ras guanosine triphosphatases that may influence various signaling pathways involving renal inflammatory, fibrogenic, proliferative, and cell-death responses. Therefore, statins exert anti-inflammatory actions in renal tissue, prevent renal scarring, and diminish mesangial or other kidney cell-type proliferation while promoting mesangial cell apoptosis. Renal antioxidant effects with consequent endothelial function regulation of renal vasculature following statin treatment may also account for pleiotropic protection against renal injury.