Fasudil Ameliorates Rhabdomyolysis-Induced Acute Kidney Injury via Inhibition of Apoptosis
Fasudil Ameliorates Rhabdomyolysis-Induced Acute Kidney Injury via Inhibition of Apoptosis
复制标题
DOI：
10.3109/0886022x.2011.601830
复制
发表时间：
2011-08
期刊：
影响因子：
3
通讯作者：
Yuan-da Wang;Li Zhang;G. Cai;Xue‐guang Zhang;Yang Lv;Q. Hong;S. Shi;Z. Yin;Xiangdi Liu;Xiang-Mei Chen
中科院分区：
文献类型：
--
作者：
Yuan-da Wang;Li Zhang;G. Cai;Xue‐guang Zhang;Yang Lv;Q. Hong;S. Shi;Z. Yin;Xiangdi Liu;Xiang-Mei Chen
在战争或自然灾害期间，横纹肌溶解导致的急性肾损伤（AKI）可以达到流行病的程度。法舒地尔可减轻缺血/再灌注引起的AKI。我们研究了早期应用法舒地尔治疗横纹肌溶解性AKI的疗效，并探讨了其可能的机制。将雄性Wistar大鼠随机分为对照组（生理盐水，7 mL/kg，灌胃）、Gly组（50%甘油，7 mL/kg，灌胃）和法舒地尔组（50%甘油，7 mL/kg，灌胃；法舒地尔，20 mg/kg体重，灌胃，从给药前72 h开始，每24 h灌胃3次）。注射甘油24 h后，用血清肌酐、血尿素氮（BUN）和组织病理学变化来评价肾脏功能。检测细胞凋亡和rho相关蛋白激酶成员（ROCK1）、磷酸酶和紧张素同源物（PTEN）、P-Akt、caspase-8、-9和-3的表达。与对照组相比，Gly组血清肌酐和BUN水平显著升高。法舒地尔治疗后两种水平均下降。法舒地尔组肾小管损伤评分明显低于Gly组，细胞凋亡明显少于Gly组。Gly组ROCK1、PTEN、caspase-8、-9、-3表达水平显著上调，法舒地尔组表达水平降低。Gly组P-Akt水平明显降低，法舒地尔组P-Akt水平明显上调。早期应用法舒地尔可通过抑制Rho激酶从而激活PI-3K/Akt通路减少横纹肌溶解相关肾损伤，从而通过内源性和外源性凋亡途径减少细胞凋亡。
During times of war or natural disasters, rhabdomyolysis leading to acute kidney injury (AKI) can assume epidemic proportions. Fasudil attenuates ischemia/reperfusion-induced AKI. We investigated the therapeutic effect of an early application of fasudil on AKI induced by rhabdomyolysis and explored the potential mechanisms. Male Wistar rats were randomly divided into a control group (saline, 7 mL/kg, i.m.), a Gly group (50% glycerol, 7 mL/kg, i.m.), and a fasudil group (50% glycerol, 7 mL/kg, i.m.; fasudil, 20 mg/kg bodyweight, i.p., three times every 24 h beginning 72 h before glycerol administration). Serum creatinine, blood urea nitrogen (BUN), and histopathological changes were used to demonstrate kidney function 24 h after the glycerol injection. Cell apoptosis and the expression of rho-associated protein kinase member (ROCK1), phosphatase and tensin homolog (PTEN), P-Akt, and caspase-8, -9, and -3 were measured. Serum creatinine and BUN levels increased significantly in Gly group compared with control group. Both levels decreased after fasudil treatment. The renal tubular damage score was significantly lower and cell apoptosis was significantly less in fasudil group compared with Gly group. The expression levels of ROCK1, PTEN, and caspase-8, -9, and -3 were upregulated significantly in Gly group, and their expression was reduced in the fasudil group. The P-Akt level was decreased in Gly group and upregulated significantly in fasudil group. Early application of fasudil reduced rhabdomyolysis-associated renal injury by inhibiting Rho kinase and thereby activating the PI-3K/Akt pathway, which decreased cell apoptosis via both the intrinsic and extrinsic apoptotic pathways.