Effects of hydrogen sulfide on myocardial fibrosis and PI3K/AKT1-regulated autophagy in diabetic rats.
Effects of hydrogen sulfide on myocardial fibrosis and PI3K/AKT1-regulated autophagy in diabetic rats.
复制标题
硫化氢对糖尿病大鼠心肌纤维化和 PI3K/AKT1 调节自噬的影响。
DOI：
10.3892/mmr.2015.4689
复制
发表时间：
2016-02
影响因子：
3.4
通讯作者：
Yang, Jun
中科院分区：
文献类型：
--
作者：
Wu, Zhixiong;Li, Fang;Zeng, Ou;Yang, Jun
心肌纤维化是糖尿病心肌损害的主要病理特征。以往的研究表明，硫化氢（H2S）在治疗各种心血管疾病方面具有有益的作用。然而，很少有研究调查H2S对糖尿病心肌纤维化的影响。本研究旨在探讨H2S对糖尿病诱导的心肌纤维化进展的影响。腹腔注射链脲佐菌素诱导大鼠糖尿病模型。硫氢化钠（NaHS）被用作H2S的外源供体。8周后，通过Western印迹分析测定胱硫醚-γ-裂解酶的表达水平，并通过苏木精-伊红染色和Masson染色评估心肌的形态学变化。羟脯氨酸含量和纤维化指标分别用碱性水解法和蛋白质印迹法测定。透射电镜下观察自噬体。自噬相关蛋白及其上游信号分子的表达水平也通过蛋白质印迹法进行了评估。本研究结果表明，糖尿病可导致心肌纤维化，心肌自噬增强，磷脂酰肌醇-4，5-二磷酸3-激酶/RAC-α丝氨酸/苏氨酸蛋白激酶（PI 3 K/AKT 1）信号通路受到抑制。与此相反，用NaHS治疗后，心肌纤维化得到改善，心肌自噬减少，PI 3 K/AKT 1通路抑制被逆转。本研究的结果表明，H2S对糖尿病诱导的心肌纤维化的保护作用可能与通过上调PI 3 K/AKT 1信号通路减弱自噬有关。
Myocardial fibrosis is the predominant pathological characteristic of diabetic myocardial damage. Previous studies have indicated that hydrogen sulfide (H2S) has beneficial effects in the treatment of various cardiovascular diseases. However, there is little research investigating the effect of H2S on myocardial fibrosis in diabetes. The present study aimed to investigate the effects of H2S on the progression of myocardial fibrosis induced by diabetes. Diabetes was induced in rats by intraperitoneal injection of streptozotocin. Sodium hydrosulfide (NaHS) was used as an exogenous donor of H2S. After 8 weeks, expression levels of cystathionine-γ-lyase were determined by western blot analysis and morphological changes in the myocardium were assessed by hematoxylin and eosin staining and Masson staining. The hydroxyproline content and fibrosis markers were determined by a basic hydrolysis method and western blot analysis, respectively. Autophagosomes were observed under transmission electron microscopy. Expression levels of autophagy-associated proteins and their upstream signaling molecules were also evaluated by western blotting. The results of the current study indicated that diabetes induced marked myocardial fibrosis, enhanced myocardial autophagy and suppressed the phosphatidylinositol-4,5-bisphosphate 3-kinase/RAC-α serine/threonine-protein kinase (PI3K/AKT1) signaling pathway. By contrast, following treatment with NaHS, myocardial fibrosis was ameliorated, myocardial autophagy was decreased and the PI3K/AKT1 pathway suppression was reversed. The results of the present study demonstrated that the protective effect of H2S against diabetes-induced myocardial fibrosis may be associated with the attenuation of autophagy via the upregulation of the PI3K/AKT1 signaling pathway.
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影响因子：
37.8
作者：
Calvert JW;Elston M;Nicholson CK;Gundewar S;Jha S;Elrod JW;Ramachandran A;Lefer DJ
通讯作者：
Lefer DJ
影响因子：
--
作者：
Zhu, Hongxin;Rothermel, Beverly A.;Hill, Joseph A.
通讯作者：
Hill, Joseph A.
影响因子：
3.4
作者：
Xiaoping Zhou;Xiang Lu;Wei-ting Xu;Jianchang Chen
通讯作者：
Xiaoping Zhou;Xiang Lu;Wei-ting Xu;Jianchang Chen
影响因子：
5
作者：
Dixon, IMC;Ju, HS;Jasmin, G
通讯作者：
Jasmin, G
影响因子：
3.6
作者：
Maroesjka Spiekman;Ewa Przybyt;J. Plantinga;S. Gibbs;B. van der Lei;M. Harmsen
通讯作者：
Maroesjka Spiekman;Ewa Przybyt;J. Plantinga;S. Gibbs;B. van der Lei;M. Harmsen