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比索洛尔通过抑制大鼠氧化应激和NF-κB信号通路对镉诱导的心肌毒性的保护作用

Protective Effects of Bisoprolol Against Cadmium-induced Myocardial Toxicity Through Inhibition of Oxidative Stress and NF-κΒ Signalling in Rats.

作者信息

Liu Jinhua, Xie Ying, Han Zhujun, Wang Hailong, Xu Wenhu

机构信息

Department of Cardiology, Central Hospital of Wuhan, Wuhan, Hubei, 430000, China.

Department of Infectious Diseases, Yanbian University Hospital, Yanji, Jilin, 133000, China.

出版信息

J Vet Res. 2021 Oct 20;65(4):505-511. doi: 10.2478/jvetres-2021-0054. eCollection 2021 Dec.

DOI:10.2478/jvetres-2021-0054
PMID:35112006
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8775740/
Abstract

INTRODUCTION

The aim of the study was to investigate the mitigative effects of bisoprolol (BIS) in cadmium-induced myocardial toxicity on oxidative stress and its inhibitive effect on nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) signalling in rats.

MATERIAL AND METHODS

Male albino Wistar rats were assigned to control, Cd, BIS 2 (2 mg/kg b.w.) and BIS 8 (8 mg/kg b.w.) groups with nine rats in each. Over four weeks, the control group was administered 1% gum acacia, all other groups received 3mg/kg b.w. CdCl dissolved in distilled water, and the BIS groups were additionally given bisoprolol in gum acacia. Blood samples were collected for biochemical estimations. Blood pressure and serum biomarker (lactate dehydrogenase, aspirate transaminase, alanine transferase and creatine kinase-MB, enzyme (superoxide dismutase, lipid hydroxy peroxidase, catalase and malondialdehyde), and tumour necrosis factor alpha (TNF-α) concentrations were measured. Western blot analysis was conducted for NF-κB and glutathione S-transferase (GST). After sacrificing the rats, cardiac tissue samples were examined histopathologically.

RESULTS

Our findings pointed to a significant decrease (P < 0.05) in the studied serum biomarkers and levels of the relevant enzymes in the BIS 8 group compared to the Cd group. A significant decrease (P < 0.05) in NF-kB p65 expression and TNF-α levels was noted in the BIS 8 group relative to the BIS 2 and Cd groups, indicating a reduction at a higher dose. In microscopy, histopathological changes in the cardiac muscles of the BIS 8 group were evident compared to those of the Cd group.

CONCLUSION

BIS seemed to have protective effects against cardiac injury induced by cadmium and could be considered a novel therapeutic drug and prognostic biomarker in the pathology of the many cardiovascular diseases caused by heavy metal intake.

摘要

引言

本研究旨在探讨比索洛尔(BIS)对镉诱导的大鼠心肌毒性的氧化应激减轻作用及其对活化B细胞的核因子κB轻链增强子(NF-κB)信号通路的抑制作用。

材料与方法

将雄性白化Wistar大鼠分为对照组、镉组、BIS 2(2毫克/千克体重)组和BIS 8(8毫克/千克体重)组,每组9只。在四周时间内,对照组给予1%阿拉伯胶,其他所有组给予溶解于蒸馏水中的3毫克/千克体重氯化镉,BIS组额外给予阿拉伯胶中的比索洛尔。采集血样进行生化检测。测量血压和血清生物标志物(乳酸脱氢酶、天冬氨酸转氨酶、丙氨酸转氨酶和肌酸激酶-MB)、酶(超氧化物歧化酶、脂质羟基过氧化物酶、过氧化氢酶和丙二醛)以及肿瘤坏死因子α(TNF-α)浓度。对NF-κB和谷胱甘肽S-转移酶(GST)进行蛋白质免疫印迹分析。处死大鼠后,对心脏组织样本进行组织病理学检查。

结果

我们的研究结果表明,与镉组相比,BIS 8组的研究血清生物标志物和相关酶水平显著降低(P < 0.05)。相对于BIS 2组和镉组,BIS 8组的NF-κB p65表达和TNF-α水平显著降低(P < 0.05),表明在较高剂量下有所降低。在显微镜下,与镉组相比,BIS 8组心肌的组织病理学变化明显。

结论

比索洛尔似乎对镉诱导的心脏损伤具有保护作用,可被视为重金属摄入导致的多种心血管疾病病理学中的一种新型治疗药物和预后生物标志物。

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