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首页> 美国卫生研究院文献>other >Amelioration of Renal Inflammation Endoplasmic Reticulum Stress and Apoptosis Underlies the Protective Effect of Low Dosage of Atorvastatin in Gentamicin-Induced Nephrotoxicity
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Amelioration of Renal Inflammation Endoplasmic Reticulum Stress and Apoptosis Underlies the Protective Effect of Low Dosage of Atorvastatin in Gentamicin-Induced Nephrotoxicity

机译：改善肾脏炎症内质网应激和细胞凋亡是阿托伐他汀低剂量对庆大霉素诱发的肾毒性的保护作用。

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Gentamicin is a commonly used aminoglycoside antibiotic. However, its therapeutic use is limited by its nephrotoxicity. The mechanisms of gentamicin-induced nephrotoxicity are principally from renal inflammation and oxidative stress. Since atorvastatin, 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, exerts lipid-lowering effects, antioxidant, anti-inflammatory as well as anti-apoptotic effects, this study aimed to investigate the protective effects of atorvastatin against gentamicin-induced nephrotoxicity. Male Sprague Dawley rats were used and nephrotoxicity was induced by intraperitoneal injection of gentamicin, 100 mg/kg/day, for 15 days. Atorvastatin, 10 mg/kg/day, was administered by orally gavage 30 min before gentamicin injection on day 1 to 15 (pretreatment) or on day 10 to15 (delayed treatment). For only atorvastatin treatment group, it was given on day 1 to 15. At the end of the experiment, kidney weight, blood urea nitrogen and serum creatinine as well as renal inflammation (NF-κB, TNFαR1, IL-6 and iNOS), renal fibrosis (TGFβ1), ER stress (calpain, GRP78, CHOP, and caspase 12) and apoptotic markers (cleaved caspase-3, Bax, and Bcl-2) as well as TUNEL assay were determined. Gentamicin-induced nephrotoxicity was confirmed by marked elevations in serum urea and creatinine, kidney hypertrophy, renal inflammation, fibrosis, ER stress and apoptosis and attenuation of creatinine clearance. Atorvastatin pre and delayed treatment significantly improved renal function and decreased renal NF-κB, TNFαR1, IL-6, iNOS and TGFβ1 expressions. They also attenuated calpain, GRP78, CHOP, caspase 12, Bax, and increased Bcl-2 expressions in gentamicin-treated rat. These results indicate that atorvastatin treatment could attenuate gentamicin-induced nephrotoxicity in rats, substantiated by the reduction of inflammation, ER stress and apoptosis. The effect of atorvastatin in protecting from renal damage induced by gentamicin seems to be more effective when it beginning given along with gentamicin or pretreatment.
机译：庆大霉素是常用的氨基糖苷类抗生素。但是，其治疗用途受到其肾毒性的限制。庆大霉素诱导的肾毒性的机制主要来自肾脏炎症和氧化应激。由于3-羟基-3-甲基戊二酰辅酶A还原酶抑制剂阿托伐他汀具有降脂，抗氧化，抗炎和抗凋亡作用，因此本研究旨在研究阿托伐他汀对庆大霉素诱导的肾毒性的保护作用。使用雄性Sprague Dawley大鼠，并通过腹膜内注射庆大霉素100mg / kg /天，持续15天来诱导肾毒性。在庆大霉素注射前第1至15天（预处理）或第10至15天（延迟治疗）前30分钟通过口服管饲法给予阿托伐他汀10 mg / kg /天。仅对阿托伐他汀治疗组在第1至15天给药。在实验结束时，应注意肾脏重量，血尿素氮和血清肌酐以及肾脏炎症（NF-κB，TNFαR1，IL-6和iNOS），确定肾纤维化（TGFβ1），ER应激（钙蛋白酶，GRP78，CHOP和caspase 12）和凋亡标记（裂解的caspase-3，Bax和Bcl-2）以及TUNEL测定。庆大霉素诱导的肾毒性通过血清尿素和肌酐的明显升高，肾脏肥大，肾脏炎症，纤维化，内质网应激和细胞凋亡以及肌酐清除率降低而得到证实。阿托伐他汀治疗前和延迟治疗可显着改善肾脏功能，并降低肾脏NF-κB，TNFαR1，IL-6，iNOS和TGFβ1的表达。他们还减弱了庆大霉素治疗大鼠的钙蛋白酶，GRP78，CHOP，胱天蛋白酶12，Bax和Bcl-2的表达。这些结果表明，阿托伐他汀治疗可减轻庆大霉素诱导的大鼠肾毒性，并通过减轻炎症，内质网应激和细胞凋亡得到证实。当开始与庆大霉素一起使用或进行预处理时，阿托伐他汀在预防庆大霉素引起的肾损害中的作用似乎更为有效。

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