Protective effects of levo-tetrahydropalmatine on hepatic ischemia/reperfusion injury are mediated by inhibition of the ERK/NF-κB pathway

被引:39
作者
Yu, Qiang [1 ,2 ,3 ]
Wu, Liwei [2 ]
Liu, Tong [2 ]
Li, Sainan [2 ]
Feng, Jiao [2 ]
Mao, Yuqing [4 ]
Fan, Xiaoming [5 ]
Guo, Chuanyong [1 ,2 ]
Wu, Jianye [1 ]
机构
[1] Tongji Univ, Sch Med, Putuo Peoples Hosp, Dept Gastroenterol, Shanghai 200060, Peoples R China
[2] Tongji Univ, Sch Med, Shanghai Peoples Hosp 10, Dept Gastroenterol, Shanghai 200072, Peoples R China
[3] Nanjing Med Univ, Sch Clin Med, Shanghai Hosp 10, Shanghai 200072, Peoples R China
[4] Shanghai Jiao Tong Univ, Sch Med, Shanghai Gen Hosp, Dept Gerontol, Shanghai 200080, Peoples R China
[5] Fudan Univ, Jinshan Hosp, Dept Gastroenterol, Shanghai 201508, Peoples R China
基金
中国国家自然科学基金;
关键词
Levo-tetrahydropalmatine; Hepatic ischemia reperfusion; Apoptosis; Autophagy; ERK/NF-kappa B pathway; ISCHEMIA-REPERFUSION INJURY; LIVER ISCHEMIA; CELL-DEATH; APOPTOSIS; AUTOPHAGY; ACTIVATION; EXPRESSION; MICE;
D O I
10.1016/j.intimp.2019.02.024
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Background: Hepatic ischemia/reperfusion (IR) injury is a common medical phenomenon that occurs during a number of clinical conditions, such as liver transplantation, severe injuries, and shock. In our study, we determined the protective functions of levo-tetrahydropalmatine (L-THP) on hepatic IR injury in mice by inhibiting the ERK/NF-kappa B signaling pathway. Methoth BALB/c mice were randomly divided into six groups as follows: normal control (NC); sham; L-THP (40 mg/kg); IR; L-THP (20 mg/kg) + IR; and L-THP (40 mg/kg) + IR. Liver tissues and sera were collected at three time points after reperfusion (2, 8, and 24 h). The liver enzyme, inflammatory factor, and other protein levels in the serum and liver tissues were detected. Results: L-THP pretreatment alleviated hepatocyte injury caused by IR and reduced the production of proinflammatory cytokines, such as IL-6 and TNF-alpha. Furthermore, L-THP could inhibit the ERK/NF-kappa B signaling pathway to attenuate hepatocyte apoptosis and autophagy. And the protective effect of L-THP is positively correlated with its dose. Conclusion: L-THP protects the liver from IR injury by inhibiting the release of inflammatory factors and alleviating liver cell apoptosis and autophagy. The protective functions of L-THP may be partly based on the downregulation of the ERK/NF-kappa B pathway.
引用
收藏
页码:435 / 445
页数:11
相关论文
共 48 条
[1]   Mouse model of liver ischemia and reperfusion injury: method for studying reactive oxygen and nitrogen metabolites in vivo [J].
Abe, Yuta ;
Hines, Ian N. ;
Zibari, Gazi ;
Pavlick, Kevin ;
Gray, Laura ;
Kitagawa, Yuko ;
Grisham, Matthew B. .
FREE RADICAL BIOLOGY AND MEDICINE, 2009, 46 (01) :1-7
[2]  
[Anonymous], 2011, nature immunology, V12, P681
[3]   Protective effects of St. John's wort in the hepatic ischemia/reperfusion injury in rats [J].
Atalay, Suleyman ;
Soylu, Belkis ;
Aykac, Asli ;
Ogunc, Ayliz Velioglu ;
Cetinel, Sule ;
Ozkan, Naziye ;
Erzik, Can ;
Sehirli, Ahmet Ozer .
TURKISH JOURNAL OF SURGERY, 2018, 34 (03) :198-204
[4]   Remote renal injury following partial hepatic ischemia/reperfusion injury in rats [J].
Behrends, Matthias ;
Hirose, Ryutaro ;
Park, Yeon Ho ;
Tan, Vivian ;
Dang, Kim ;
Xu, Fengyung ;
Park, Se Hun ;
Niemann, Claus U. .
JOURNAL OF GASTROINTESTINAL SURGERY, 2008, 12 (03) :490-495
[5]   15-Deoxy-Δ12,14-prostaglandin J2 alleviates hepatic ischemia-reperfusion injury in mice via inducing antioxidant response and inhibiting apoptosis and autophagy [J].
Chen, Kan ;
Li, Jing-jing ;
Li, Sai-nan ;
Feng, Jiao ;
Liu, Tong ;
Wang, Fan ;
Dai, Wei-qi ;
Xia, Yu-jing ;
Lu, Jie ;
Zhou, Ying-qun ;
Guo, Chuan-yong .
ACTA PHARMACOLOGICA SINICA, 2017, 38 (05) :672-687
[6]   Recent development in studies of tetrahydroprotoberberines: Mechanism in antinociception and drug addiction [J].
Hongyuan Chu ;
Guozhang Jin ;
Eitan Friedman ;
Xuechu Zhen .
Cellular and Molecular Neurobiology, 2008, 28 (4) :491-499
[7]   Effects of Partial Liver Ischemia Followed by Global Liver Reperfusion on the Remote Tissue Expression of Nitric Oxide Synthase: Lungs and Kidneys [J].
Correia Miranda, L. E. ;
Capellini, V. K. ;
Reis, G. S. ;
Celotto, A. C. ;
Carlotti, C. G., Jr. ;
Evora, P. R. B. .
TRANSPLANTATION PROCEEDINGS, 2010, 42 (05) :1557-1562
[8]  
Curcio R., 2015, BIOMED RES INT, V2015
[9]   Molecular mechanisms of liver ischemia reperfusion injury: Insights from transgenic knockout models [J].
Datta, Gourab ;
Fuller, Barry J. ;
Davidson, Brian R. .
WORLD JOURNAL OF GASTROENTEROLOGY, 2013, 19 (11) :1683-1698
[10]   Salidroside mediates apoptosis and autophagy inhibition in concanavalin A-induced liver injury [J].
Feng, Jiao ;
Niu, Peiqin ;
Chen, Kan ;
Wu, Liwei ;
Liu, Tong ;
Xu, Shizan ;
Li, Jingjing ;
Li, Sainan ;
Wang, Wenwen ;
Lu, Xiya ;
Yu, Qiang ;
Liu, Ning ;
Xu, Ling ;
Wang, Fan ;
Dai, Weiqi ;
Xia, Yujing ;
Fan, Xiaoming ;
Guo, Chuanyong .
EXPERIMENTAL AND THERAPEUTIC MEDICINE, 2018, 15 (06) :4599-4614