摘要目的 探讨外源性硫化氢(H2S)供体硫氢化钠(NaHS)对慢性心力衰竭大鼠心脏结构及功能的影响.方法 雄性SD大鼠47只,随机数字表法分为分流组(11只)、假手术组(8只)、分流+ NaHS组(10只)、假手术+NaHS组(8只)和分流+酚妥拉明组(10只).经腹主动脉-下腔静脉穿刺术建立容量负荷增加致慢性心力衰竭大鼠动物模型.手术后8周观察各组大鼠血流动力学指标,右室心肌细胞显微及超微结构的变化,心肌细胞外基质胶原成分的变化,测定大鼠右室心肌羟脯氨酸含量.结果 分流后8周,分流组大鼠右室收缩压(RVSP)、右室舒张末压(RVEDP)均明显高于假手术组和分流+ NaHS组(单位:mm Hg,35.2±3.9比21.4±3.7、28.1±2.7,32±5比21±4、26±4,均P＜0.05,1 mm Hg =0.133 kPa);而右室内压最大上升和下降速率显著均低(单位:mm Hg/s,1528±113比2336±185、1835±132,1331±107比2213±212、1768±116,均P＜0.05).镜下可见,分流组心肌纤维排列紊乱,部分心肌纤维溶解、消失,并有炎性细胞浸润.电镜下分流组可见心肌纤维增粗,粗细不均;部分线粒体高度肿胀及空泡形成;肌质网轻度扩张.偏光显微镜下可见分流组与假手术组比较,胶原含量较多,以Ⅰ型胶原纤维明显.分流组予NaHS干预后,大鼠心肌纤维损伤较前好转,心肌纤维改变缓解;心肌胶原含量减少,以Ⅰ型胶原纤维含量减少为著.分流组右室心肌羟脯氨酸含量明显高于假手术组和分流+ NaHS组(单位:mg· g-1·pro,1.32±0.25比0.89 ±0.18、0.83 ±0.19,均P＜0.05).结论 气体分子H2S可以改善容量负荷增加致慢性心力衰竭大鼠心功能及心脏结构,其机制可能通过扩张血管及影响细胞外基质胶原代谢发挥作用.

abstractsObjective To explore the effects of sodium hydrosulfide ( NaHS),a hydrogen sulphide (H2S) donor,on cardiac functions and structures in rats with chronic heart failure induced by volume overload and examine its influence on cardiac remodelling.Methods A total of 47 SD rats ( 120 - 140 g) were randomly divided into 5 groups:shunt group ( n =11 ),sham group ( n =8),shunt + NaHS group ( n =10),sham + NaHS group ( n =8) and shunt + phentolamine group (n =10).The rat model of chronic heart failure was induced by abdominal aorta-inferior vena cava puncture.At Week 8 post-operation,hemodynamic parameters,microstructures and ultrastructures of myocardial tissues were analyzed.Extracellular collagen content in myocardial tissues was analyzed after Sirius red staining.Right ventricular hydroxyproline concentration was determined and compared.Results At Week 8 post-operation,compared with the sham operation and shunt + NaHS groups,the shunt group showed significantly increased right ventricular systolic pressure (RVSP) and right ventricular end diastolic pressure (RVEDP) ( mm Hg:35.2 ±3.9 vs 21.4 ±3.7 and 28.1 ±2.7,32 ±5 vs 21 ±4 and 26 ±4,all P ＜0.05,1 mm Hg =0.133 kPa).The RV peak rate of contraction and relaxation markedly decreased ( RV ± dp/dt max) ( mm Hg/s:1528 ± 113 vs 2336 ± 185 and 1835 ± 132,1331 ± 107 vs 2213 ± 212 and 1768 ± 116,all P ＜ 0.05).It was found microscopically that myocardial fibers in the shunt group were irregularly arranged,partially cytolyzed and infiltrated by inflammatory cells.Electron microscopy revealed that myocardial fibers thickened non-uniformly in the shunt group,some fiber mitochondria were highly swollen and contained vacuoles.And sarcoplasmic reticulum appeared slightly dilated.Polarized microscopy indicated that,collagen content (particularly type-Ⅰ collagen) increased in the shunt group compared with the sham operation group.Additionally,compared with the shunt group,the shunt and NaHS treatment groups showed an amelioration of myocardial damage,an alleviation of myocardial fiber changes and a decrease in myocardial collagen content (particularly type-Ⅰ collagen).Compared with the sham operation and shunt + NaHS groups,the shunt group displayed increased right ventricular hydroxyproline ( mg · g-1 · pro:1.32 ±0.25 vs 0.89 ±0.18 and 0.83 ±0.19,all P ＜ 0.05 ).Conclusion H2S may improve cardiac functions and ameliorate cardiac structures in rats with chronic heart failure probably through dilating the blood vessels and affecting the extracellular collagen metabolism.