摘要
背景丙戊酸钠(sodium valproate,VPA)在严重烫伤早期心脏功能保护研究中取得很大进展,缺氧诱导因子-1α(hypoxia-inducible factor-1α,HIF-1α)与心肌损伤密切相关,VPA与HIF-1α在严重烫伤心肌损伤中的作用机制仍有待探索。目的研究VPA是否通过影响HIF-1α表达而减轻严重烫伤大鼠早期心肌损伤。方法88只雄性SD大鼠随机分为假烫+0.9%氯化钠注射液组(NN组,n=24)、烫伤+0.9%氯化钠注射液组(SN组,n=32)、烫伤+VPA组(SV组,n=32);采用沸水法致50%总体表面积Ⅲ度烫伤,伤后即刻,NN组、SN组腹腔内注射0.25 mL 0.9%氯化钠注射液,SV组腹腔内给予VPA治疗(300 mg/kg,溶于0.25 mL 0.9%氯化钠注射液)。分别于伤后3 h和6 h处死各组8只大鼠,取腹主动脉血,测定肌酸激酶同工酶(creatine kinase isoenzyme,CK-MB)水平;取心肌组织,观察心肌组织病理变化及凋亡心肌细胞,测定心肌组织内肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)水平,检测心肌组织内HIF-1α、BNIP3、裂解半胱氨酸天冬氨酸蛋白酶-3(Cleaved caspase-3)蛋白表达水平;各组剩余大鼠观察12 h生存情况。结果生存分析显示,伤后12 h,SV组平均生存时间(550.00±17.32)min,生存率50%,优于SN组[平均生存时间(400.00±29.76)min,生存率0](P<0.05)。与NN组比较,SN组伤后3 h和6 h的CK-MB、心肌细胞凋亡率、TNF-α、Cleaved caspase-3、HIF-1α和BNIP3蛋白表达均增加(P均<0.05);与SN组比较,SV组伤后CK-MB、心肌细胞凋亡率、TNF-α降低,Cleaved caspase-3、HIF-1α及BNIP3蛋白表达水平降低(P均<0.05);SV组病理损伤较SN组有所改善。结论VPA能提高严重烫伤大鼠伤后早期生存率,减轻心肌损伤,可能与下调大鼠心肌组织内HIF-1α的表达有关。
Background Sodium valproate(VPA)has made great progress in the study of cardiac function protection in the early stage of severe scald injury,hypoxia-inducible factor-1α(HIF-1α)is closely related to myocardial injury,and the mechanism of action of VPA and HIF-1αin myocardial injury in severe scald injury remains to be explored.Objective To investigate whether VPA attenuates early myocardial injury in severely scalded rats by affecting HIF-1αexpression.Methods Eighty-eight male SD rats were randomly divided into normal+0.9%NaCl group(NN group,n=24),scald+0.9%NaCl group(SN group,n=32),and scald+VPA group(SV group,n=32);III°scald with 50%of total surface area were caused by boiling water method,and NN and SN group were intraperitoneally injected with 0.25 mL of NaCl,and the SV group was intraperitoneally given VPA(300 mg/kg,dissolved in 0.25 mL of 0.9%NaCl)immediately after the injury.Eight rats in each group were executed at 3h and 6h after injury,and creatine kinase isoenzyme(CK-MB)levels were measured by taking blood from the abdominal aorta;myocardial tissues were taken for observation of myocardial tissue pathology and apoptotic cardiomyocytes,the levels of tumor necrosis factor-alpha(TNF-α),the expression levels of HIF-1α,BCL2/adenovirus E1B interacting protein 3(BNIP3),and cleaved caspase-3;the 12-hour survival rate was observed in the remaining rats in each group.Results Survival analysis showed that at 12 h after injury,SV group had a mean survival time of(550.00±17.32)min and a survival rate of 50%,which were superior to that of SN group(mean survival time of[400.00±29.76]min and a survival rate of 0%,P<0.05).Compared with NN group,CK-MB,cardiomyocyte apoptosis rate,TNF-α,cleaved caspase-3,HIF-1α,and BNIP3 protein expression levels increased in SN group at 3h and 6h post-injury(all P<0.05);compared with SN group,CK-MB,cardiomyocyte apoptosis rate,TNF-αwere decreased,and cleaved caspase-3,HIF-1α,and BNIP3 protein expression levels were decreased in SV group(all P<0.05);pathologic injuries were improved in SV group compared to SN group.Conclusion VPA improves early post-injury survival and attenuates myocardial injury in severely scalded rats,which may be related to the down-regulation of HIF-1αexpression in rat myocardial tissue.
作者
孟祥熙
刘翔宇
吴育寿
温海玲
胡森
郑金光
MENG Xiangxi;LIU Xiangyu;WU Yushou;WEN Hailing;HU Sen;ZHENG Jinguang(Department of Burn and Plastic Surgery,Affiliated Hospital of Chengde Medical University,Chengde 067000,Hebei Pronince,China;Department of Burn and Plastic Surgery,the Fourth Medical Center of PLA General Hospital,Beijing 100048,China;Chinese PLA Medical School,Beijing 100853,China;Medical Innovation Research Department of PLA General Hospital,Beijing 100853,China)
出处
《解放军医学院学报》
2025年第2期186-190,204,共6页
Academic Journal of Chinese PLA Medical School
基金
承德市科学技术研究与发展计划项目(201904A106)。
关键词
烫伤
丙戊酸钠
心肌损伤
凋亡
缺氧诱导因子-1Α
scald
sodium valproate
myocardial injury
apoptosis
hypoxia-inducible factor-1α
