气体信号分子硫化氢通过调控p38MAPK-microRNA通路抑制糖尿病性心肌病的心肌损伤

我们已证实内源性气体信号分子硫化氢（H2S）具细胞保护作用（包括心肌保护），其作用机制与抗氧化、抗炎症及抑制p38丝裂原激活蛋白激酶（MAPK）通路等有关。最近的研究证实，p38MAPK在糖尿病性心肌病（DCM）的发病机制中起重要的作用。因此，我们推测H2S能通过抑制p38MAPK对抗DCM引起的心肌细胞损伤。为此，本研究探讨：（1）microRNAs(miR-133a和miR-21)和内源性H2S是否参与DCM的发病机制？（2）外源性H2S（NaHS，是H2S的供体）对DCM心肌细胞凋亡、炎症、线粒体损伤、氧化应激的抑制作用及microRNAs表达的影响；（3）H2S能否通过调控microRNAs及p38MAPK通路抑制DCM的心肌损伤（包括细胞凋亡和炎症等），试图从microRNA水平和分子水平阐明DCM心肌损伤的新机制及H2S对DCM的抑制作用与机制，为防治DCM拓展新思路。

We have demonstrated that endogenous gas signaling molecule hydrogen sulfide(H2S) has cytoprotective effects, including cardioprotection, the mechanisms responsible for this are associated with antioxidation, anti-inflammation and inhibition of p38MAPK pathway, etc. Recently, it was revealed that p38MAPK pathway plays an important role in the pathogenesis of DCM. Thus, we hypothesize that H2S might prevent from cardiomyocyte injury in DCM by inhibiting p38MAPK pathway.The aim of the presents study is to explore （1）whether mcroRNAs(miR-133a and miR-21)and endogenous H2S are involved in the pathogenesis of DCM? (2)inhibitory effects of exogenous H2S (NaHS, a donor of H2S) on cardiomyocyte apoptosis, inflammation, mitochondrial damage and oxidative stress, as well as influence of NaHS on microRNAs expression;(3)whether H2S inhibits myocardiac injuries, including cell apoptosis and inflammation, etc. in DCM by modulating microRNAs and p38MAPK pathway. Based on these experiments, we try to explain the new mechanisms for myocardiac injury of DCM and the inhibitory effects of H2S on DCM and the relative mechanisms from microRNA level and molecular level. The present study would provide a new insight into prevention and treatment for DCM.