Zhiling Li1, Ming Gao1, Bingchang Yang1, Huali Zhang2, Kangkai Wang2, Zuoliang Liu1, Xianzhong Xiao3, Mingshi Yang4. 1. Translational Medicine Center of Sepsis, The Third Xiangya Hospital, Central South University, Changsha, 410013, People's Republic of China; Department of Critical Care Medicine, The Third Xiangya Hospital, Central South University, Changsha, 410013, People's Republic of China; Laboratory of Shock, Department of Pathophysiology, Xiangya School of Medicine, Central South University, Changsha, 410078, People's Republic of China. 2. Translational Medicine Center of Sepsis, The Third Xiangya Hospital, Central South University, Changsha, 410013, People's Republic of China; Laboratory of Shock, Department of Pathophysiology, Xiangya School of Medicine, Central South University, Changsha, 410078, People's Republic of China. 3. Translational Medicine Center of Sepsis, The Third Xiangya Hospital, Central South University, Changsha, 410013, People's Republic of China; Department of Critical Care Medicine, The Third Xiangya Hospital, Central South University, Changsha, 410013, People's Republic of China; Laboratory of Shock, Department of Pathophysiology, Xiangya School of Medicine, Central South University, Changsha, 410078, People's Republic of China. Electronic address: xianzhongxiao152@163.com. 4. Translational Medicine Center of Sepsis, The Third Xiangya Hospital, Central South University, Changsha, 410013, People's Republic of China; Department of Critical Care Medicine, The Third Xiangya Hospital, Central South University, Changsha, 410013, People's Republic of China; Laboratory of Shock, Department of Pathophysiology, Xiangya School of Medicine, Central South University, Changsha, 410078, People's Republic of China. Electronic address: mingshiyang524@163.com.
Abstract
BACKGROUND: Sepsis is commonly associated with excessive stimulation of host immune system and result in multi-organ failure dysfunction. Naringin has been reported to exhibit a variety of biological effects. The present study aimed to investigate the protective effect of naringin on sepsis-induced injury of intestinal barrier function in vivo and in vitro. METHODS: Mice were randomly divided into 4 groups named sham (n = 20), CLP + vehicle (n = 20), CLP + NG (30 mg/kg) (n = 20) and CLP + NG (60 mg/kg) (n = 20) groups. Sepsis was induced by cecal ligation and puncture (CLP). H&E staining and transmission electron microscopy (TEM) were performed to observe intestinal mucosal morphology. ELISA was used to determine the intestinal permeability and inflammatory response in vivo and in vitro. Western blot and RhoA activity assay were performed to determine the levels of tight junction proteins and the activation of indicated signaling pathways. MTT assay was used to determine cell viability. RESULTS: Naringin improved survival rate of CLP mice and alleviated sepsis-induced intestinal mucosal injury. Furthermore, naringin improved impaired intestinal permeability and inhibited the release of TNF-α and IL-6, while increased IL-10 level in CLP mice and lipopolysaccharide (LPS)-stimulated MODE-K cells in a dose-dependent manner. Naringin increased the expression of tight junction proteins ZO-1 and claudin-1 via RhoA/ROCK/NF-κB/MLCK/MLC signaling pathway in vivo and in vitro. CONCLUSION: Naringin improved sepsis-induced intestinal injury via RhoA/ROCK/NF-κB/MLCK/MLC signaling pathway in vivo and in vitro.
BACKGROUND: Sepsis is commonly associated with excessive stimulation of host immune system and result in multi-organ failure dysfunction. Naringin has been reported to exhibit a variety of biological effects. The present study aimed to investigate the protective effect of naringin on sepsis-induced injury of intestinal barrier function in vivo and in vitro. METHODS:Mice were randomly divided into 4 groups named sham (n = 20), CLP + vehicle (n = 20), CLP + NG (30 mg/kg) (n = 20) and CLP + NG (60 mg/kg) (n = 20) groups. Sepsis was induced by cecal ligation and puncture (CLP). H&E staining and transmission electron microscopy (TEM) were performed to observe intestinal mucosal morphology. ELISA was used to determine the intestinal permeability and inflammatory response in vivo and in vitro. Western blot and RhoA activity assay were performed to determine the levels of tight junction proteins and the activation of indicated signaling pathways. MTT assay was used to determine cell viability. RESULTS:Naringin improved survival rate of CLPmice and alleviated sepsis-induced intestinal mucosal injury. Furthermore, naringin improved impaired intestinal permeability and inhibited the release of TNF-α and IL-6, while increased IL-10 level in CLPmice and lipopolysaccharide (LPS)-stimulated MODE-K cells in a dose-dependent manner. Naringin increased the expression of tight junction proteins ZO-1 and claudin-1 via RhoA/ROCK/NF-κB/MLCK/MLC signaling pathway in vivo and in vitro. CONCLUSION:Naringin improved sepsis-induced intestinal injury via RhoA/ROCK/NF-κB/MLCK/MLC signaling pathway in vivo and in vitro.
Authors: Vanessa A Areco; Romina Kohan; Germán Talamoni; Nori G Tolosa de Talamoni; María E Peralta López Journal: World J Gastroenterol Date: 2020-06-28 Impact factor: 5.742