Tubeimoside I improves endothelial function in sepsis via activation of SIRT3

作者全名："Yang, Xiyang; Li, Xingbing; Luo, Minghao; Li, Chang; Huang, Longxiang; Li, Xiang; Huang, Bi; Shen, Jian; Luo, Suxin; Yan, Jianghong"

作者地址："[Yang, Xiyang; Li, Xingbing; Luo, Minghao; Li, Chang; Huang, Longxiang; Li, Xiang; Huang, Bi; Shen, Jian; Luo, Suxin] Chongqing Med Univ, Affiliated Hosp 1, Dept Cardiol, Chongqing, Peoples R China; [Yang, Xiyang; Li, Xingbing; Luo, Minghao; Li, Chang; Huang, Longxiang; Shen, Jian; Luo, Suxin; Yan, Jianghong] Chongqing Med Univ, Inst Life Sci, Chongqing, Peoples R China"

通信作者："Luo, SX (corresponding author), Chongqing Med Univ, Affiliated Hosp 1, Dept Cardiol, Chongqing, Peoples R China.; Luo, SX; Yan, JH (corresponding author), Chongqing Med Univ, Inst Life Sci, Chongqing, Peoples R China."

来源：LABORATORY INVESTIGATION

ESI学科分类：CLINICAL MEDICINE

WOS号：WOS:000625535600001

JCR分区：Q1

影响因子：5

年份：2021

卷号：101

期号：7

开始页：897

结束页：907

文献类型：Article

关键词：　

摘要："Sepsis is life-threatening organ dysfunction caused by a deregulated host response to infection. Endothelial dysfunction is the initial factor leading to organ dysfunction and it is associated with increased mortality. There is no effective drug to treat sepsis-induced endothelial dysfunction. In this study, we detected a favorable effect of tubeimoside I (TBM) in ameliorating sepsis-induced endothelial dysfunction. To unveil the mechanism how TBM protects against sepsis-induced endothelial dysfunction, we examined TBM's effects on oxidative stress and apoptosis both in vivo and in vitro. TBM treatment alleviated oxidative stress by decreasing NOX2 and Ac-SOD2/SOD2 and decreased apoptosis by inhibiting cleaved caspse3 and Bax/Bcl-2. Notably, sepsis induced a significant decrease of SIRT3 expression in vascular endothelium, while TBM treatment reversed SIRT3 expression. To clarify whether TBM provides protection via SIRT3, we knockdown SIRT3 using siRNA before TBM treatment. Then, the cytoprotective effects of TBM were largely abolished by siSIRT3. This suggests that SIRT3 plays an essential role in TBM's endothelial protective effects and TBM might be a potential drug candidate to treat sepsis-induced endothelial dysfunction. The authors show that intraperitoneal injection of tubeimoside I (TBM) alleviates the endothelial dysfunction caused by sepsis. Their results suggest that TBM functions by reducing oxidative stress and apoptosis via SIRT3, an NAD-dependent deacetylase. TBM is therefore a promising new therapeutic agent against sepsis-induced endothelial dysfunction."

基金机构："National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [31400999, 81400355, 81770479]; Scientific and Technological Research Program of Chongqing Municipal Education Commission [KJQN201800417]; Basic Science and Frontier Technology Research Project of Chongqing Science and Technology Commission [cstc2020jcyj-msxmX1091, cstc2017jcyjAX0330]"

基金资助正文："This work was supported by the National Natural Science Foundation of China (31400999, 81400355, and 81770479), the Scientific and Technological Research Program of Chongqing Municipal Education Commission (KJQN201800417), and Basic Science and Frontier Technology Research Project of Chongqing Science and Technology Commission (cstc2020jcyj-msxmX1091 and cstc2017jcyjAX0330)."