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蛇毒心脏毒素经口给药改善阿霉素诱导的大鼠慢性肾脏病。

Ameliorating Adriamycin-Induced Chronic Kidney Disease in Rats by Orally Administrated Cardiotoxin from Naja naja atra Venom.

机构信息

The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, China.

Department of Pharmacology and Laboratory of Aging and Nervous Diseases, Soochow University School of Medicine, Suzhou 215123, Jiangsu, China.

出版信息

Evid Based Complement Alternat Med. 2014;2014:621756. doi: 10.1155/2014/621756. Epub 2014 Apr 30.

Abstract

Previous studies reported the oral administration of Naja naja atra venom (NNAV) reduced adriamycin-induced chronic kidney damage. This study investigated the effects of intragastric administrated cardiotoxin from Naja naja atra venom on chronic kidney disease in rats. Wistar rats were injected with adriamycin (ADR; 6 mg/kg body weight) via the tail vein to induce chronic kidney disease. The cardiotoxin was administrated daily by intragastric injection at doses of 45, 90, and 180  μ g/kg body weight until the end of the protocol. The rats were placed in metabolic cages for 24 hours to collect urine, for determination of proteinuria, once a week. After 6 weeks, the rats were sacrificed to determine serum profiles relevant to chronic kidney disease, including albumin, total cholesterol, phosphorus, blood urea nitrogen, and serum creatinine. Kidney histology was examined with hematoxylin and eosin, periodic acid-Schiff, and Masson's trichrome staining. The levels of kidney podocin were analyzed by Western blot analysis and immunofluorescence. We found that cardiotoxin reduced proteinuria and can improve biological parameters in the adriamycin-induced kidney disease model. Cardiotoxin also reduced adriamycin-induced kidney pathology, suggesting that cardiotoxin is an active component of NNAV for ameliorating adriamycin-induced kidney damage and may have a potential therapeutic value on chronic kidney disease.

摘要

先前的研究报道称,蝮蛇蛇毒(Naja naja atra venom,NNAV)的口服给药可减轻阿霉素诱导的慢性肾损伤。本研究旨在探讨蝮蛇心脏毒素经胃内给药对大鼠慢性肾脏病的影响。Wistar 大鼠通过尾静脉注射阿霉素(ADR;6mg/kg 体重)诱导慢性肾病。心脏毒素以 45、90 和 180 μ g/kg 体重的剂量通过胃内注射每日给药,直至方案结束。大鼠被置于代谢笼中 24 小时,以每周一次的频率收集尿液,用于测定蛋白尿。6 周后,处死大鼠以确定与慢性肾脏病相关的血清谱,包括白蛋白、总胆固醇、磷、血尿素氮和血清肌酐。通过苏木精和伊红、过碘酸希夫和 Masson 三色染色检查肾脏组织学。通过 Western blot 分析和免疫荧光分析来分析肾脏足细胞素的水平。我们发现心脏毒素可减少蛋白尿,并能改善阿霉素肾病模型中的生物学参数。心脏毒素还可减轻阿霉素引起的肾脏病理学改变,提示心脏毒素是 NNAV 中改善阿霉素诱导的肾脏损伤的活性成分,可能对慢性肾脏病具有潜在的治疗价值。

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