内源性硫化氢对阿霉素心肌病大鼠心肌结构的影响  

The effect of endogenous hydrogen sulfide on myocardial structure of rats with adriamycin-induced dilated cardiomyopathy

作　　者：苏钰雯[1] 杜军保[1] 韩薇[1] 汤秀英[2] 唐朝枢[3] 

机构地区：[1]北京大学第一医院儿科,北京100034 [2]北京大学第一医院电镜室,北京100034 [3]北京大学第一医院心血管病研究所,北京100034

出　　处：《临床儿科杂志》2007年第10期828-831,共4页Journal of Clinical Pediatrics

基　　金：国家杰出青年科学基金资助项目(No.30425010);国家重点基础研究发展规划资助项目(No.2006CB503807);国家自然科学基金资助项目(No.30630031)

摘　　要：目的通过给予内源性硫化氢(hydrogen sulfide,H2S)生成酶抑制剂DL-propargylglycine(PPG)抑制内源性H2S生成对阿霉素(adriamycin,ADR)心肌病大鼠心肌结构的影响,探讨内源性H2S在阿霉素心肌病发病中的作用。方法雄性Wistar大鼠33只,随机分为3组:①阿霉素组(ADR组,n=12),腹腔注射ADR,每次2.5mg/kg,1次/周,共用药10周;②ADR+PPG组(n=12),ADR用药方法同ADR组,同时经腹腔注射PPG,30mg/(kg·d),连续用药10周;③对照组(n=9),用相同容量的生理盐水代替ADR,给药方法同ADR组,共10周。于第10周处死大鼠,取心肌组织制作病理切片,分别于光镜及透射电镜下观察其显微以及超微结构,并采用硫敏感电极法测定其血清及心肌组织中H2S含量,比较其中的差异。结果病理结果显示正常对照组心肌纤维结构清晰;ADR组心肌细胞变性、线粒体和肌浆网水肿、细胞内空泡增多,呈心肌病样改变;而ADR+PPG组心肌组织病理改变较ADR组大鼠更为显著。H2S含量测定显示ADR组大鼠血清及心肌组织H2S含量均明显低于对照组(P<0.001);而ADR+PPG组血清及心肌组织H2S含量降低更为明显,其中血清H2S含量与ADR组相比差异有统计学意义(P<0.001)。结论内源性H2S对大鼠心肌组织可能具有保护作用,内源性H2S生成减少可能是大鼠阿霉素心肌病形成过程中的重要原因之一。Objectives To investigate the role of endogenous hydrogen sulfide （H2S） in the pathogenensis of adriamycin （ADR）-induced dilated cardiomyopathy by the administration of DL-propargylglycine （PPG）, a specific inhibitor of cystathionine-γ-lyase, to deprive the endogenous production of H2S in rats. Methods Totally 33 weight- matched adult male Wistar rats were randomly divided into 3 groups. （1） In the ADR group in = 12）, 2.5 mg/kg of ADR was injected intraperitoneally once a week for 10 weeks （total dose of 25 mg/kg） . （2） In the ADR ＋ PPG group in = 12）, ADR was administered as above but with a PPG solution injected at a dosage of 30 μmol/（kg·d） . （3） In the control group （n = 9）, an equivalent volume of saline was administered weekly. The animals were sacrificed on the 10 th week and histological examination was performed. H2S concentrations of serum and myocardial tissues were detected by modified sulfide electrode method. Results Pathological examination by light and transmission electron microscopy demonstrated clear histological structure of myocardial tissues in the control group. Typical features of cardiomyopathy were found in the ADR group, including cardiac muscle cell degeneration, mitochondrial and sarcoplasmic reticular edema and numerous intracellular vacuoles. All the pathological changes of myocardial tissues developed more dramatically in the ADR ＋ PPG group than that in the ADR group. At the same time, both H2S concentrations of serum and myocardial tissues in the ADR group were significantly decreased compared with those in the control group （P 〈 0.001 ） . Both H2S concentrations of serum and myocardial tissues in the ADR ＋ PPG group were much lower than those in the ADR group. In particular, the serum level of H2S significantly decreased （P 〈 0.001 ） . Conclusions Endogenous H2S might protect myocardium from injury. Down-regulation of the expression of endogenous H2S might play an important role in the development of adriamycin-induced

关 键 词：硫化氢 阿霉素心肌病 心肌组织超微结构 

分 类 号：R725.4[医药卫生—儿科]