伏立诺他腹腔注射对严重烧伤早期大鼠心肌损伤和细胞凋亡的干预作用及其机制  

Interventional effects of intraperitoneal injection of vorinostat on myocardial injury and apoptosis in early stage of rats with lethal scald

作　　者：孟祥熙 温海玲[1] 郑金光 吴忠隐 胡森[4] 孙奎[1] MENG Xiangxi;WEN Hailing;ZHENG Jinguang;WU Zhongyin;HU Sen;SUN Kui(Department of Burn and Plastic Surgery,The Affiliated Hospital of Chengde Medical University,Chengde 067000,China;不详)

机构地区：[1]承德医学院附属医院烧伤整形科,河北承德067000 [2]解放军总医院第四医学中心烧伤整形医学部 [3]承德医学院附属医院血管外科 [4]解放军总医院医学创新研究部创伤修复与组织再生研究中心

出　　处：《山东医药》2022年第8期30-33,共4页Shandong Medical Journal

基　　金：国家自然科学基金项目(81471872);承德市科学技术研究与发展计划项目(201904A106)。

摘　　要：目的观察组蛋白去乙酰化酶抑制剂伏立诺他(SAHA)对严重烧伤早期大鼠心肌损伤及细胞凋亡的干预作用,并探讨其机制。方法雄性SD大鼠24只,随机分为假烫组、烫伤组、SAHA组,每组8只。烫伤组、SAHA组采用沸水水浴法建立50%TBSAⅢ°烫伤大鼠模型,烫伤组和SAHA组分别于伤后腹腔内注射0.25 mL生理盐水、7.5 mg/kg的SAHA;假烫组以37℃水浴代替沸水,后腹腔内注射0.25 mL生理盐水。伤后6 h取大鼠腹主动脉血,检测血浆肌酸激酶同工酶(CK-MB);处死动物,取心肌组织,TUNEL法测算心肌细胞凋亡率,Western blotting法检测心肌细胞中的Caspase-3、诱导型一氧化氮合成酶(iNOS)、组蛋白3第9位乙酰化的赖氨酸(Ac-H3K9)蛋白,ELISA法检测一氧化氮(NO)水平。结果烫伤组血浆CK-MB水平、心肌细胞凋亡率及心肌细胞中NO、Caspase-3、iNOS蛋白表达高于假烫组,Ac-H3K9蛋白表达低于假烫组(P均<0.05);SAHA组血浆CK-MB水平、心肌细胞凋亡率及心肌细胞中NO、Caspase-3、iNOS蛋白表达低于烫伤组,Ac-H3K9蛋白表达高于烫伤组(P均<0.05)。结论SAHA能减轻致死性烫伤大鼠心肌损伤,减少心肌细胞凋亡,其机制可能与增加心肌细胞组蛋白乙酰化水平,下调Caspase-3、iNOS蛋白表达,减少NO生成有关。Objective To observe the effects of histone deacetylase inhibitor vorinostat(SAHA)on myocardial injury and apoptosis in early stage of rats with lethal scald and to investigate the mechanism.Methods Twenty-four male Sprague-Dawley(SD)rats were selected and randomly divided into the sham scald group,the scald group,and SAHA group,with 8 in each group.In the scald group and SAHA group,we established 50%total body surface area(TBSA)Ⅲ°scald injury rat models with boiled water.The rats in the scald group and SAHA group were intraperitoneally injected with 0.25 mL normal saline(NS)or 7.5 mg/kg SAHA;37℃water instead of boiled water was used for the rats in the sham scald group,followed by intraperitoneal injection of 0.25 mL NS.At 6 h after scald,blood in each group was drawn from the abdominal aorta to detect the level of creatine kinase isoenzymes(CK-MB);the rats were sacrificed and we collected the cardical tissues.We calculated the rate of myocardial apoptosis in each group with TUNEL method,the level of histone acetylation and the expression levels of Caspase-3 and inducible nitric oxide synthase(iNOS)were detected by Western blotting,and the level of NO in myocardial cells was detected by ELISA.Results The level of CK-MB,the rate of myocardial apoptosis,the level of NO,and the expression levels of Caspase-3 and iNOS in the scald group were significantly higher than those in the sham scald group,but the expression of Ac-H3K9 protein was significantly lower(all P<0.05).The level of CK-MB,the rate of myocardial apoptosis,the level of NO,the expression levels of Caspase-3 and iNOS were significantly lower than those in the scald group,and the expression of Ac-H3K9 protein was significantly higher than that of the scald group(all P<0.05).Conclusions SAHA can protect cardiac function in severely scalded rats,and decrease cardiomyocyte apoptosis,which may be related to the increased level of histone acetylation,up-regulated expression of Caspase-3 and NO,and inhibition of the production of iNOS.

关 键 词：烫伤 伏立诺他 组蛋白去乙酰化酶抑制剂 心肌细胞 细胞凋亡 

分 类 号：R644[医药卫生—外科学]