硫化氢对阿霉素心肌损伤模型中心肌缝隙连接和连接蛋白的影响

Effect of hydrogen sulfide on cardiac gap junction remodeling and connexin expression in doxorubicin-induced cardiotoxicity in mice

目的在小鼠阿霉素心肌损伤模型中,探讨硫化氢对心肌连接蛋白(connexins,Cx)表达及缝隙连接超微结构的影响。方法 10周龄、雄性C57BL/6J小鼠一次性腹腔注射大剂量阿霉素15mg·kg-1或生理盐水,注射后2h即开始每天予以硫化氢供体药物NaHS(1mg·kg-1,i.p.)或生理盐水。14天后通过超声心动图评估小鼠的左心功能情况,随后处死小鼠并留取血浆和左心室组织,通过透射电镜观察心肌缝隙连接的超微结构,采用RT-PCR和Western Blot技术检测心肌Cx43和Cx45的表达水平,并观察了心肌的氧化应激和炎症水平以及血浆心肌酶谱的变化。结果在阿霉素心肌损伤模型中,心肌Cx43和Cx45的表达水平明显降低,心肌缝隙连接的数目减少且分布稀疏。予以NaHS干预后,心肌Cx43和Cx45的表达水平显著上调,心肌缝隙连接的重构明显改善,同时阿霉素所致的心肌氧化应激和炎症反应、心肌损伤和心功能障碍亦显著改善。结论硫化氢可能通过上调心肌连接蛋白的表达和抑制心肌缝隙连接的重构,在阿霉素心肌损伤中发挥一定的心脏保护作用。

Objective To investigate the effect of hydrogen sulfide on cardiac gap junction remodeling and connexin expression in doxorubicin-induced cardiotoxicity. Methods Ten-week old, male C57BL/6J mice were randomly given doxorubicin (15mg·kg-1, i.p.) or saline (i.p.). Two hours after doxorubicin or saline injection, either NaHS (1 mg·kg-1, i.p.) or saline (i.p.) were administered daily for consecutive 14 days. After fourteen days, the mice were sacrificed. Thereafter, expression levels of connexin 43 (Cx43) and c...