胱硫醚-γ-裂解酶/硫化氢通路在小鼠病毒性心肌炎中的表达

Expression of cystathionine-γ-lyase/hydrogen sulfide pathway in CVB3-induced myocarditis in mice

目的近年研究发现硫化氢(H2S)在血管活性调节、炎症反应、细胞增殖凋亡、缺血再灌注、氧化应激等方面起重要作用,而在心肌炎发病机制中也存在这些基本的病理生理过程,因此本研究检测胱硫醚-γ-裂解酶(CSE)/H2S通路在小鼠病毒性心肌炎中的表达。方法 6周龄近交系雄性Balb/c小鼠随机分为对照组(n=25)和病毒性心肌炎组(n=30),分别给予PBS和10-5.69TCID50/mLCVB30.1mL注射,第4和10天各随机取10只小鼠处死并取血和心脏标本,检测血清H2S和心肌H2S生成活性,心肌常规苏木素-伊红染色,免疫组化检测CSE蛋白表达。结果在急性病毒性心肌炎小鼠模型中,血清H2S及心肌H2S生成活性较对照组升高(P<0.05),心肌CSE蛋白表达亦增加(P<0.05)。结论在急性小鼠CVB3心肌炎中CSE和其下游产物H2S水平上调,CSE/H2S通路表达上调可能通过多个环节参与疾病的发病。

Objective Previous studies have shown that hydrogen sulfide （H2S） plays key roles in a number of biological processes,including vasorelaxation,inflammation,apoptosis,ischemia/reperfusion and oxidative stress,which are involved in the pathogenesis of myocarditis.This study aimed to examine the expression of cystathionine-γ-lyase （CSE） /H2S pathway in mice with viral myocarditis.Methods Six-week-old inbred male mice were randomly assigned to control （n=25） and myocarditis group （n=30）.The myocarditis and the control groups were inoculated intraperitoneally with 0.1 mL 10-5.69TCID50 /mL CVB3 or vehicle （PBS） alone respectively.Ten mice were sacrificed 4 and 10 days after injection.Blood and heart specimens were harvested for measuring the content of serum H2S and the H2S production rates in cardiac tissues.Heart sections were stained with hematoxylin and eosin.Immunohistochemisty was used to detect the CSE protein expression in the heart.Results In the myocarditis group,the serum H2S content and H2S production rates in cardiac tissues were significantly higher than those in the control group 4 and 10 days after injection （P〈0.05）.The expression of CSE protein in the heart in the myocarditis group was also significantly higher than that in the control group （P〈0.05）.Conclusions CSE and its downstream production H2S increase in mice with acute viral myocarditis.The increased expression of CSE/H2S pathway might be involved in the pathogenesis of viral myocarditis.