气体信号分子硫化氢对吸烟诱导左室重构的保护作用及相关机制研究

We previously established a passive smoking rat model which was intragastricly administrated with NaHS, a donor of hydrogen sulfide (H2S). Our findings demonstrated that H2S could significantly reduce myocardial oxidative damage and cellular apoptosis, improve myocardial fibrosis and left ventricular systolic function, which consequently attenuated left ventricular remodeling in rats. Based on the above results, we need to further explore the potential mechanisms by which H2S protects against smoking-induced left ventricular remodeling. In the present study, we will investigate the protective effects of H2S against left ventricular remodeling in smoking rats by means of echocardiography, hemodynamic detection and histologic pathology. Then we will detect oxidative stress, apoptosis and related signaling pathways (Nrf2/ARE and PI3K/Akt) to reveal the protective mechanisms of H2S against smoking-induced left ventricular remodeling. Moreover, we will also explore the role of Nrf2/ARE and PI3K/Akt signaling pathways in H2S-induced attenuation of myocardial oxidative damage and cellular apoptosis using myocardial cell lines H9c2 transfected with Nrf2-siRNA and PI3K-siRNA and exposed to cigarette smoke extract and NaHS.

本课题组先前利用H2S供体NaHS对被动吸烟大鼠进行干预，发现H2S能够减轻心肌氧化损伤与细胞凋亡，显著改善心肌纤维化与左室收缩功能，从而减轻大鼠左室重构。在上述研究基础上，我们需要进一步探讨H2S对吸烟诱导左室重构的保护机制。为此，本项目将分别进行体内研究与体外研究：1、建立被动吸烟大鼠模型，给予NaHS进行干预，运用超声心动图、血流动力学、组织病理学等方法进一步证实H2S对吸烟诱导左室重构的保护作用；然后通过检测氧化应激、细胞凋亡及相关信号通路Nrf2/ARE、PI3K/Akt，初步阐明H2S对吸烟诱导左室重构的保护机制；2、培养H9c2心肌细胞，分别转染Nrf2-siRNA、PI3K-siRNA以沉默Nrf2、PI3K基因，然后利用香烟提取物、NaHS对H9c2细胞进行干预，进一步揭示Nrf2/ARE、PI3K/Akt信号通路在H2S减轻心肌细胞氧化损伤与凋亡中的作用。

本课题组先前利用H2S供体NaHS对被动吸烟大鼠进行干预，发现H2S能够减轻心肌氧化损伤与细胞凋亡，显著改善心肌纤维化与左室收缩功能，从而减轻大鼠左室重构。在上述研究基础上，我们进一步探讨H2S对吸烟诱导左室重构的保护机制。为此，本项目分别进行体内研究与体外研究：1、建立被动吸烟大鼠模型，给予NaHS进行干预，运用超声心动图、血流动力学、组织病理学等方法进一步证实H2S对吸烟诱导左室重构的保护作用；然后通过检测氧化应激、细胞凋亡及相关信号通路Nrf2/ARE、PI3K/Akt，初步阐明H2S对吸烟诱导左室重构的保护机制；2、培养H9c2心肌细胞，分别转染Nrf2-siRNA、PI3K-siRNA以沉默Nrf2、PI3K基因，然后利用香烟提取物、NaHS对H9c2细胞进行干预，进一步揭示Nrf2/ARE、PI3K/Akt信号通路在H2S减轻心肌细胞氧化损伤与凋亡中的作用。本研究为今后H2S在心室重构防治中的应用提供了重要的实验依据。