机构地区:[1]空军军医大学唐都医院心血管内科,西安710038
出 处:《山西医科大学学报》2021年第5期580-587,共8页Journal of Shanxi Medical University
基 金:空军军医大学唐都医院创新发展基金前沿探索项目(2019QYTS011)。
摘 要:目的探究和厚朴酚(honokiol,HKL)处理对重度烧伤大鼠早期心肌损伤的作用及其机制。方法40只SD大鼠随机分为假烧伤组(sham)、假烧伤+和厚朴酚处理组(sham+HKL)、烧伤组(burn)、烧伤+和厚朴酚处理组(burn+HKL),每组10只。采用背部烫伤法造成大鼠30%体表面积Ⅲ度烧伤来构建动物模型。待烧伤处理24 h后,用小动物超声仪检测大鼠心脏舒缩功能(LVEF、LVFS和E/A值);HE染色法观察心肌组织形态结构改变;用血生化分析仪检测大鼠血清中LDH和CK-MB水平;ELISA法检测大鼠血清中炎症因子IL-1β、IL-6、TNF-α及黏附分子ICAM-1、VCAM-1的含量;特定试剂盒检测大鼠血清心肌组织中SOD活性和MDA的含量;DHE染色法观察心肌组织内活性氧(ROS)产量;TUNEL染色法检测心肌细胞凋亡程度;Western blot法检测Nrf2和cleaved Caspase-3的蛋白表达水平。结果与sham组相比,burn组大鼠心脏舒缩功能显著降低,表现为LVEF、LVFS和E/A值明显下降(P<0.05),且大鼠血清LDH及CK-MB水平明显上升(P<0.05);血清炎症因子IL-1β、IL-6、TNF-α及黏附分子ICAM-1、VCAM-1的含量显著升高(P<0.05);心肌组织ROS产量及MDA含量明显增加,SOD活性显著减低(P<0.05);心肌细胞凋亡率明显增加,凋亡蛋白cleaved Caspase-3表达显著上调(P<0.05)。与burn组相比,burn+HKL组大鼠心脏舒缩功能显著改善(P<0.05),心肌损伤标志物LDH及CK-MB水平明显减低(P<0.05);血清炎症因子及黏附分子的含量显著降低(P<0.05);心肌组织氧化应激水平显著下降(P<0.05);心肌细胞凋亡被显著抑制(P<0.05)。结论HKL处理可明显减轻重度烧伤大鼠早期心肌损伤,其机制可能与抑制氧化应激和炎症反应有关。Objective To investigate the protective effects of honokiol(HKL)against early myocardial injury in severely burned rats and explore its underlying mechanism.Methods Forty SD rats were grouped as follows:sham group,sham+HKL group,burn group and burn+HKL group,with n=10 in each group.The rats were burned on the back to establish third degree burns comprising 30%of the total burned surface area(TBSA).Twelve hours after HKL treatment,the carotid function was recorded by the Vevo 770 ultrasound instrument(LVEF,LVFS and E/A ratio).Morphological and structural changes of myocardium were observed by HE staining.Serum LDH and CK-MB levels were measured by the blood biochemical analyzer.The contents of IL-1β,IL-6,TNF-α,ICAM-1 and VCAM-1 were detected by ELISA kits.The activity of SOD and the content of MDA in myocardial tissue were measured by special commercial kits.The production of reactive oxygen species(ROS)in myocardial tissue was observed by DHE staining.The apoptotic ratio of cardiomyocytes was detected by TUNEL staining.Protein expression levels of Nrf2 and cleaved Caspase-3 were detected by Western blot.Results Compared with sham group,the cardiac function(including E/A ratio,LVEF and LVFS)and pathological changes of myocardium were reduced in burn group(P<0.05).Compared with sham group,the serum levels of myocardial damage markers LDH and CK-MB,inflammatory cytokines IL-1,IL-6,TNF-αand adhesion molecules ICAM-1,VCAM-1 were all increased in burn group(P<0.05).Compared with sham group,ROS production and MDA content were significantly elevated,while SOD activity was decreased in cardiac tissue in burn group(P<0.05).Compared with sham group,the apoptotic ratio of cardiomyocytes and the expression of apoptotic protein cleaved Caspase-3 were promoted in burn group(P<0.05).Compared with burn group,the cardiac function and pathological changes of myocardium were significantly improved(P<0.05),the serum levels of myocardial damage markers,inflammatory cytokines and adhesion molecules were significantly decreased(P<0.0
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