硫化氢对柯萨奇病毒B3心肌炎小鼠血红素加氧酶-1/一氧化碳通路的影响  

The impact of hydrogen sulfide on the heme oxygenase-1/carbon monoxide system in Coxsackie virus B3-induced myocarditis in mice

作　　者：张松跃[1] 吴婷婷[1] 任跃[1] 夏天和[1] 吴蓉洲[1] 

机构地区：[1]温州医科大学附属第二医院育英儿童医院儿童心脏中心温州医科大学心脏发育与转化医学研究所,325027

出　　处：《中华心血管病杂志》2017年第9期765-769,共5页Chinese Journal of Cardiology

基　　金：浙江省科技厅公益性技术应用研究计划项目（2014C33164）

摘　　要：目的 探讨硫化氢（H2S）对柯萨奇病毒B3（CVB3）心肌炎小鼠血红素加氧酶-1（HO-1）/一氧化碳通路的影响.方法 清洁级近交系雄性Balb/c小鼠70只,分为正常组（n=10）、心肌炎组（n=20）、炔丙基甘氨酸组（PAG组,n=20）和硫氢化钠组（NaHS组,n=20）.心肌炎组、PAG组和NaHS组分别在第0天每只小鼠腹腔注射0.1 ml10-5 69TCID50m·ml-1的CVB3建立心肌炎模型,从第0天起PAG组予以炔丙基甘氨酸（PAG）40 mg·kg-1·d-1腹腔注射,NaHS组予以硫氢化钠（NaHS） 50 μmol·kg-1·d-1腹腔注射,心肌炎组予以等量磷酸盐缓冲液（PBS）腹腔注射.对照组从第0天起每只小鼠每日腹腔注射不含病毒的等量灭菌PBS液.观察至接种后第10天各组取10只小鼠,记录小鼠体重,采血后处死留取心脏标本并记录其质量.采用心脏质量/体重比值衡量心肌水肿程度,以反应心肌炎症程度.苏木素伊红染色观察小鼠心肌病理改变并计算炎症积分.检测各组小鼠血清碳氧血红蛋白（COHb）表达水平.逆转录聚合酶链反应检测心肌细胞中HO-1 mRNA的表达水平.结果 （1）各组小鼠心肌病理学特征：正常组小鼠心肌细胞结构正常,心肌纤维排列整齐,胞浆丰富均匀,横纹清晰,间质无水肿.心肌炎组、PAG组和NaHS组小鼠心肌内均可见心肌细胞坏死崩解,周围伴有大量炎症细胞浸润,以单核细胞和淋巴细胞为主,PAG组心肌细胞坏死及炎症浸润更为明显,坏死灶内可见蓝色钙化颗粒,胞核和细胞轮廓消失,NaHS组炎症较轻,心肌炎症细胞浸润范围较心肌炎组和PAG组小.（2）各组小鼠心脏质量/体重比值和心肌炎症积分：心肌炎组、PAG组和NaHS组小鼠心脏质量/体重比值均明显高于正常组（P均＜0.05）,其中PAG组又明显高于心肌炎组（P＜0.05）,而NaHS组则明显低于心肌炎组（P=0.001）.心肌炎组、PAG组和NaHS组小鼠心肌炎症积分均明显高于正常组（P均＜0.05）,但NaHS组�Objective To explore the impact of hydrogen sulfide （H2S） on the heme oxygenase-1/carbon monoxide pathway in Coxsackie virus B3 （CVB3）-induced murine myocarditis （VMC） model.Method A total of 70 inbred male Balb/c mouse （4-6 weeks old） were randomized into the following four groups：Normal,VMC,PAG and NaHiS （n =10 for Normal,n =20 for VMC,PAG and NaHiS groups）.Mice in Normal group were non-infected mice treated with intraperitoneal injection of sterile phosphate-buffered saline daily for 10 days.Mice in VMC group received intraperitoneal CVB3 injection （0.1 ml l0-569TCID5om · ml-1 · d-1 and PBS for 10 days）,and mice in PAG group received additional intraperitoneal DL-proparglygylcine injection （40 mg · kg-1 · d-1 for 10 days）,mice in NaHS group received additional intraperitoneal NaHS injection （50 μmol · kg-1 · d-1 for 10 days）.All mice were sacrificed on day 10th,and body weight and heart weight,the ratio of heart weight to body weight were compared among groups.Pathological changes of heart tissues were observed microscopically by HE and the histopathologic scores were valued.The content of COHb was tested after the gathering of blood specimens while reverse transcription-polymerase chain reaction was used to detect myocardial HO-1 mRNA expression.Results （1） Pathological findings in myocardium：hearts sections in Normal group were normal and no inflammatory cells and necrosis were found.A notable cellular infiltration,interstitial edema,vascular hyperemia and necrosis were observed in heart section of VMC,PAG and NaHS group.Extensive inflammations and larger area of myocardial cells necrosis were evidenced in PAG group and above changes were significantly reduced in NaHS group.（2） Comparison of the ratio of heart weight to body weight and histological scores of myocardium：the ratio was significantly higher in the VMC,PAG,NaHS groups than in Normal group （P ＜0.05）,which was higher in PAG group and lower in NaHS group as compared with VMC group （both P

关 键 词：心肌炎 硫化氢 碳氧血红蛋白 血红素加氧酶-1 一氧化碳 

分 类 号：R542.21[医药卫生—心血管疾病]