摘要
目的探讨神经氨酸酶1(NEU1)对脂多糖(LPS)诱导的大鼠心肌损伤的作用及分子机制。方法选取2023年6-7月于武汉市第三医院动物房饲养24只6~7周雄性Sprague-Dawley大鼠,大鼠购自湖北省疾控中心实验中心,首先采取NUE1抑制剂OSE(20 mg/kg)或等量生理盐水连续灌胃预处理3 d后,腹腔注射LPS(10 mg/kg)或等量生理盐水,12 h后行心脏离体灌流检查。取血清,ELISA检测心肌损伤标志物cTnT、CK-MB;取心脏,Western检测心肌组织中Bcl-2、Bax蛋白表达水平。结果超声心动图结果显示,LPS组大鼠心脏射血分数及缩短分数明显降低,而LPS+OSE组大鼠的心脏功能得到改善。血清酶学结果显示,LPS组大鼠心肌损伤标志物较对照组明显升高,而NEU1抑制剂OSE组则显著降低心肌损伤标志物的水平。心脏电生理结果显示,LPS腹腔注射后,大鼠心脏的动作电位(APD)及有效不应期(ERP)显著缩短;与LPS组相比,LPS+OSE组大鼠的平均ERP及APD50、APD90水平显著增加。Western结果示LPS腹腔注射后,大鼠心肌组织中Bax的蛋白水平表达明显升高,Bcl-2蛋白则表达较少;与LPS组相比,LPS+OSE组大鼠心肌组织中的Bcl-2表达增加,Bax蛋白水平降低。结论NEU1抑制剂预处理可通过减轻炎症和细胞凋亡,改善LPS诱导造成的心肌损伤,从而保护心脏功能。
Objective To investigate the mechanism of neuraminidase 1(NEU1)on lipopolysaccharide(LPS)-induced myocardial injury in rats.Methods From June to July 2023,24 male Sprague-Dawley rats aged 6-7 weeks were raised in the animal room of Wuhan Third Hospital.The rats were purchased from the experimental center of Hubei Provincial Center for Disease Control and Prevention.Firstly,taking NUE1 inhibitor OSE(20 mg/kg)or equivalent amount of saline by continuous oral pretreatment for 3 d,after that,LPS(10 mg/kg)or an equivalent amount of saline was injected intraperitoneally,and the heart was examined by ex vivo perfusion after 12 h.Serum was taken and ELISA was performed to detect the markers of myocardial injury,cTnT and CK-MB.The heart was taken,and the expression levels of Bcl-2 and Bax proteins in myocardial tissues were detected by western.Results Echocardiographic results showed that the cardiac ejection fraction and shortening fraction were significantly reduced in the LPS group,while the cardiac function was improved in the LPS+OSE group.ELISA results showed that myocardial injury markers were significantly elevated in the LPS group compared with the control group,whereas the levels of myocardial injury markers were significantly reduced in the LPS+OSE group.Cardiac electrophysiological results showed that after intraperitoneal injection of LPS,the action potential(APD)and effective response period(ERP)of the rat heart were significantly shortened,and the average ERP and the levels of APD50 and APD90 of the rat heart in the LPS+OSE group were significantly increased compared with those of the LPS group.The Western results showed that after intraperitoneal injection of LPS,the expression of the protein level of Bax was significantly increased,while the expression of Bcl-2 protein was lower in the rat heart.elevated,while Bcl-2 protein was less expressed;compared with the LPS group,Bcl-2 expression in the myocardial tissue of rats in the LPS+OSE group was increased,and Bax protein level was decreased.Conclusion NEU1 inhibitor pretreatment can improve LPS-induced myocardial injury by attenuating inflammation and apoptosis,thus protecting cardiac function.
作者
王秀昆
陈小丽
杨波
WANG Xiu-kun;CHEN Xiao-li;YANG Bo(Department of Cardiology,Renmin Hospital of Wuhan University,Cardiovascular Research Institute,Wuhan University,Hubei Key Laboratory of Cardiology,Wuhan 430060,China)
出处
《中国心血管病研究》
CAS
2024年第3期284-288,共5页
Chinese Journal of Cardiovascular Research
基金
国家自然科学基金(82170316、82200520)。
关键词
神经氨酸酶1
脂多糖
凋亡
Neuraminidase 1
Lipopolysaccharide
Apoptosis