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Cobrotoxin from Naja naja atra Venom Ameliorates Adriamycin Nephropathy in Rats

机译:眼镜蛇毒中的Cobrotoxin改善了大鼠阿霉素肾病

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摘要

Chronic kidney disease (CKD) becomes a global health problem with high morbidity and mortality. Adriamycin- (ADR-) induced rodent chronic nephropathy is a classic experimental model of human minimal lesion nephrotic syndrome. The present study investigated the effect of cobrotoxin (CTX) on ADR-induced nephropathy. Rats were given 6 mg/kg ADR once through the tail vein to replicate ADR nephropathy model. CTX was administered to rats daily by placing a fast dissolving CTX membrane strip under the tongue starting from 5 days prior to ADR administration until the end of experiment. The results showed that CTX ameliorated the symptoms of ADR nephropathy syndrome with reduced body weight loss, proteinuria, hypoalbuminemia, dyslipidemia, serum electrolyte imbalance, oxidative stress, renal function abnormities, and kidney pathological lesions. Anti-inflammatory cytokine IL-10 expression was elevated after CTX administration in ADR nephropathy model. CTX inhibited the phosphorylation of IκB-α and NF-κB p65 nuclear translocation. Meanwhile, CTX upregulated the protein level of podocyte-specific nephrin and downregulated the level of fibrosis-related TGF-β. These findings suggest that CTX may be a potential drug for chronic kidney diseases.
机译:慢性肾脏病(CKD)成为全球性的健康问题,发病率和死亡率很高。阿霉素-(ADR-)诱导的啮齿动物慢性肾病是人类微小病变肾病综合征的经典实验模型。本研究调查了Cobrotoxin(CTX)对ADR诱发的肾病的影响。通过尾静脉给大鼠一次6μmg/ kg ADR,以复制ADR肾病模型。从ADR给药前5天到实验结束,每天通过在舌下放置快速溶解的CTX膜条将CTX给药于大鼠。结果表明,CTX改善了ADR肾病综合征的症状,体重减轻,蛋白尿,低白蛋白血症,血脂异常,血清电解质失衡,氧化应激,肾功能异常和肾脏病理病变减轻。在ADR肾病模型中给予CTX后,抗炎细胞因子IL-10表达升高。 CTX抑制IκB-α和NF-κBp65核易位的磷酸化。同时,CTX上调了足细胞特异性肾素的蛋白水平,下调了与纤维化相关的TGF-β的水平。这些发现表明,CTX可能是治疗慢性肾脏疾病的潜在药物。

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