Baicalein pretreatment reduces liver ischemia/reperfusion injury via induction of autophagy in rats

被引:59
作者
Liu, Anding [1 ,2 ]
Huang, Liang [3 ]
Guo, Enshuang [4 ,5 ]
Li, Renlong [4 ,5 ]
Yang, Jiankun [1 ]
Li, Anyi [6 ]
Yang, Yan [1 ]
Liu, Shenpei [1 ]
Hu, Jifa [1 ]
Jiang, Xiaojing [5 ]
Dirsch, Olaf [2 ]
Dahmen, Uta [2 ]
Sun, Jian [7 ]
机构
[1] Huazhong Univ Sci & Technol, Tongji Hosp, Tongji Med Coll, Ctr Med Expt, 1095 Jiefang Ave, Wuhan 430030, Peoples R China
[2] Univ Jena, Dept Gen Visceral & Vasc Surg, Expt Transplantat Surg, 1 Drackendorfer Str, D-07747 Jena, Germany
[3] Huazhong Univ Sci & Technol, Tongji Hosp, Dept Blood Transfus, Tongji Med Coll, 1095 Jiefang Ave, Wuhan 430030, Peoples R China
[4] Southern Med Univ, Grad Sch, 1023 Shatai Nan Rd, Guangzhou 510515, Guangdong, Peoples R China
[5] Wuhan Gen Hosp Guangzhou Mil Command, Dept Infect Dis, 627 Wuluo Rd, Wuhan 430070, Peoples R China
[6] Huazhong Univ Sci & Technol, Tongji Hosp, Tongji Med Coll, Ctr Expt Anim, 1095 Jiefang Ave, Wuhan 430030, Peoples R China
[7] Sun Yat Sen Univ, Sun Yat Sen Mem Hosp, Dept Biliopancreat Surg, 107 Yanjiang Xi Rd, Guangzhou 510120, Guangdong, Peoples R China
来源
SCIENTIFIC REPORTS | 2016年 / 6卷
基金
高等学校博士学科点专项科研基金;
关键词
ISCHEMIA-REPERFUSION INJURY; HEME OXYGENASE-1; IMPAIRED AUTOPHAGY; CELL-DEATH; KAPPA-B; PROTECTS; INHIBITION; DAMAGE; APOPTOSIS; PATHWAY;
D O I
10.1038/srep25042
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
We previously demonstrated that baicalein could protect against liver ischemia/reperfusion (I/R) injury in mice. The exact mechanism of baicalein remains poorly understood. Autophagy plays an important role in protecting against I/R injury. This study was designed to determine whether baicalein could protect against liver I/R injury via induction of autophagy in rats. Baicalein was intraperitoneally injected 1 h before warm ischemia. Pretreatment with baicalein prior to I/R insult significantly blunted I/R-induced elevations of serum aminotransferase levels and significantly improved the histological status of livers. Electron microscopy and expression of the autophagic marker LC3B-II suggested induction of autophagy after baicalein treatment. Moreover, inhibition of the baicalein-induced autophagy using 3-methyladenine (3-MA) worsened liver injury. Furthermore, baicalein treatment increased heme oxygenase (HO)-1 expression, and pharmacological inhibition of HO-1 with tin protoporphyrin IX (SnPP) abolished the baicalein-mediated autophagy and the hepatocellular protection. In primary rat hepatocytes, baicalein-induced autophagy also protected hepatocytes from hypoxia/reoxygenation injury in vitro and the beneficial effect was abrogated by 3-MA or Atg7 siRNA, respectively. Suppression of HO-1 activity by SnPP or HO-1 siRNA prevented the baicalein-mediated autophagy and resulted in increased hepatocellular injury. Collectively, these results suggest that baicalein prevents hepatocellular injury via induction of HO-1-mediated autophagy.
引用
收藏
页数:12
相关论文
共 30 条
[1]   Heme Oxygenase-1-Mediated Autophagy Protects Against Hepatocyte Cell Death and Hepatic Injury from Infection/Sepsis in Mice [J].
Carchman, Evie H. ;
Rao, Jayashree ;
Loughran, Patricia A. ;
Rosengart, Matthew R. ;
Zuckerbraun, Brian S. .
HEPATOLOGY, 2011, 53 (06) :2053-2062
[2]   Baicalein is neuroprotective in rat MCAO model: Role of 12/15-lipoxygenase, mitogen-activated protein kinase and cytosolic phospholipase A2 [J].
Cui, Lili ;
Zhang, Xiangjian ;
Yang, Rui ;
Liu, Lingling ;
Wang, Lina ;
Li, Min ;
Du, Wei .
PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR, 2010, 96 (04) :469-475
[3]   Functions of autophagy in normal and diseased liver [J].
Czaja, Mark J. ;
Ding, Wen-Xing ;
Donohue, Terrence M., Jr. ;
Friedman, Scott L. ;
Kim, Jae-Sung ;
Komatsu, Masaaki ;
Lemasters, John J. ;
Lemoine, Antoinette ;
Lin, Jiandie D. ;
Ou, Jing-Hsiung James ;
Perlmutter, David H. ;
Randall, Glenn ;
Ray, Ratna B. ;
Tsung, Allan ;
Yin, Xiao-Ming .
AUTOPHAGY, 2013, 9 (08) :1131-1158
[4]   Preconditioning, Organ Preservation, and Postconditioning to Prevent Ischemia-Reperfusion Injury to the Liver [J].
de Rougemont, Olivier ;
Lehmann, Kuno ;
Clavien, Pierre-Alain .
LIVER TRANSPLANTATION, 2009, 15 (10) :1172-1182
[5]   Ischemic preconditioning induces autophagy and limits necrosis in human recipients of fatty liver grafts, decreasing the incidence of rejection episodes [J].
Degli Esposti D. ;
Sebagh M. ;
Pham P. ;
Reffas M. ;
Poüs C. ;
Brenner C. ;
Azoulay D. ;
Lemoine A. .
Cell Death & Disease, 2011, 2 (1) :e111-e111
[6]   Dual role of chloroquine in liver ischemia reperfusion injury: reduction of liver damage in early phase, but aggravation in late phase [J].
Fang, H. ;
Liu, A. ;
Dahmen, U. ;
Dirsch, O. .
CELL DEATH & DISEASE, 2013, 4 :e694-e694
[7]   Hepatic ischemia/reperfusion injury - a fresh look [J].
Fondevilla, C ;
Busuttil, RW ;
Kupiec-Weglinski, JW .
EXPERIMENTAL AND MOLECULAR PATHOLOGY, 2003, 74 (02) :86-93
[8]   Autophagy: cellular and molecular mechanisms [J].
Glick, Danielle ;
Barth, Sandra ;
Macleod, Kay F. .
JOURNAL OF PATHOLOGY, 2010, 221 (01) :3-12
[9]   Hepatoprotective effects of baicalein against CCl4-induced acute liver injury in mice [J].
Huang, Hai-Li ;
Wang, Ya-Jing ;
Zhang, Qing-Yu ;
Liu, Bin ;
Wang, Fang-Yuan ;
Li, Jing-Jing ;
Zhu, Run-Zhi .
WORLD JOURNAL OF GASTROENTEROLOGY, 2012, 18 (45) :6605-6613
[10]   Protective effects of baicalein on tert-butyl hydroperoxide-induced hepatic toxicity in rat hepatocytes [J].
Hwang, JM ;
Tseng, TH ;
Tsai, YY ;
Lee, HJ ;
Chou, FP ;
Wang, CJ ;
Chu, CY .
JOURNAL OF BIOMEDICAL SCIENCE, 2005, 12 (02) :389-397