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生姜给药对顺铂诱导的大鼠心脏毒性的影响:光镜和电镜研究。

The influence of ginger administration on cisplatin-induced cardiotoxicity in rat: Light and electron microscopic study.

机构信息

Department of Medical Histology & Cell Biology, Faculty of Medicine, Mansoura University, Egypt.

Department of Medical Histology & Cell Biology, Faculty of Medicine, Mansoura University, Egypt.

出版信息

Acta Histochem. 2019 Jul;121(5):553-562. doi: 10.1016/j.acthis.2019.04.013. Epub 2019 May 6.

DOI:10.1016/j.acthis.2019.04.013
PMID:31068261
Abstract

Cisplatin is a powerful chemotherapeutic agent. Cardiotoxicity is one of its major adverse effects. Ginger is a commonly used element in herbal medicine due to its anti-oxidant potentials. This study was planned to assess the histological changes induced by cisplatin in the cardiac muscle and to clarify the possible protective influence of ginger intake. Forty rats were divided into four groups. Control; given normal saline. Ginger; received oral ginger (500 mg/kg/day) for 12 days. Cisplatin; given cisplatin (2 mg/kg/day) daily by intraperitoneal injection for 1 week. Cisplatin + Ginger; received ginger (500 mg/kg/day) for 5 days prior to and concomitant with intraperitoneal injection of cisplatin (2 mg/kg/day) for 1 week. Serum levels of lactate dehydrogenase (LDH) and creatine kinase (CK) were estimated. Cardiac specimens were subjected to light, electron microscopic and immunohistochemical study using anti-P53 and anti-TNF-α antibodies. Morphometric and statistical studies were done. In Cisplatin group, cardiac muscle fibers appeared disorganized, disrupted or degenerated with pyknotic nuclei and showed a significant rise in the number of anti-P53 positive nuclei. Significant increments in the percent area of collagenous fibers and TNF-α immune-expression were observed. Ultrastructurally, the cardiomyocytes displayed disorganized or interrupted myofibrils, swollen disrupted mitochondria, and widening of intercalated discs. Serum levels of CK and LDH were significantly elevated. Cisplatin + Ginger group showed marked improvement in the cardiac histology and ultrastructure, downregulation of P53 and TNF-α immune-expressions and reduction in CK and LDH serum levels. In conclusion, ginger exhibits a protective effect against cisplatin cardiotoxicity mostly through its anti-apoptotic, anti-oxidant and anti-inflammatory properties.

摘要

顺铂是一种强有力的化疗药物。心脏毒性是其主要的不良反应之一。生姜由于其抗氧化潜力,是草药中常用的元素。本研究旨在评估顺铂对心肌引起的组织学变化,并阐明生姜摄入的可能保护作用。将 40 只大鼠分为四组。对照组;给予生理盐水。生姜组;连续 12 天口服生姜(500mg/kg/天)。顺铂组;每天腹腔注射顺铂(2mg/kg/天),共 1 周。顺铂+生姜组;在腹腔注射顺铂(2mg/kg/天)的前 5 天和同时给予生姜(500mg/kg/天),共 1 周。测定血清乳酸脱氢酶(LDH)和肌酸激酶(CK)水平。心脏标本进行光镜、电镜和免疫组织化学研究,使用抗 P53 和抗 TNF-α 抗体。进行形态计量学和统计学研究。在顺铂组中,心肌纤维出现排列紊乱、断裂或变性,核固缩,抗 P53 阳性核的数量明显增加。胶原纤维和 TNF-α免疫表达的百分比面积显著增加。超微结构显示,心肌细胞的肌原纤维排列紊乱或中断,线粒体肿胀、断裂,闰盘增宽。血清 CK 和 LDH 水平显著升高。顺铂+生姜组心脏组织学和超微结构明显改善,P53 和 TNF-α 免疫表达下调,CK 和 LDH 血清水平降低。总之,生姜通过其抗凋亡、抗氧化和抗炎特性表现出对顺铂心脏毒性的保护作用。

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