|
|
|
|
|
| Establishment of a rat model of acute liver injury induced by LPS/D-GaLN |
| Liu Jiang-kai, Liu Xiang-li, Li Cong-cong, Dong Yong-chun, Liu Shao-ying, Liu Xue-tao |
| Department of Gastroenterology, First Affiliated Hospital of Henan University of Traditional Chinese Medicine, Zhengzhou 450000, China |
|
|
|
|
Abstract Objective Establish an animal model of acute liver injury induced by lipopolysaccharide (LPS)/D- galactosidase (D-GaLN) in rats. Methods Thirty-two Sprague-Dawly (SD) rats were randomly divided into 4 groups, intraperitoneal injection of different doses of LPS and 300 mg/kg D-GaLN, the best model dose was screened by observing the survival time of rats. After determined the optimal dose, 40 SD rats were randomly divided into 8 h, 24 h, 48 h, 72 h and blank control groups. The model group received intraperitoneal injection of LPS/D-GaLN, while the control group received normal saline. 8 h, 24 h, 48 h and 72 h were used to detect serum ALT, AST, TNF-a and IL-6 in rats, pathological changes of liver tissues were also observed. Result LPS (30μg/kg)/D-GaLN (300 mg/kg) was determined as the best dosage by observing the survival time and liver histopathology of rats. The levels of serum ALT, AST and inflammatory factors TNF-α and IL-6 were significantly increased, peaked at 24 h, and then decreased gradually. Compared with the control group, there was significant difference (P<0.05). Liver pathology showed hepatocyte swelling and degeneration, flaky necrosis and fusion necrosis. Conclusion The animal model of acute endotoxin-induced liver injury by LPS/D-GaLN in rats has been successfully established, which is conducive to the observation of the therapeutic effect of hepatoprotective drugs and the further study of its mechanism.
|
|
|
|
|
|
| ［1］Pijls KE， Jonkers DM， Elamin EE， et al. Intestinal epithelial barrier function in liver cirrhosis: an extensive review of the literature［J］. Liver Int, 2013, 33(10):1457-1469．
［2］Kuhla A， Eipel c， Siebert N， et al． Hepatocellular apoptosis is mediated by TNF alpha-dependent Fas/Fasligand cytotoxicity in a murine model of acute liver failure［J］. Apoptosis, 2008, 13(12):1427．
［3］Shao B， Munford RS， Kitchens R， et al． Hepatic uptake and deacylation of the LPS in blood borne LPS-lipoprotein complexes ［J］.Innate Immun, 2012, 18(6):825-833．
［4］Zhang S, Yang N, Ni S, et al． Pretreatment of lipopolysaccharide(LPS) ameliorates D-GalN/LPS induced acute liver failure through TLR4 signaling pathway［J］. Int J Clin Exp Pathol, 2014, 7(10): 6626-6634．
［5］Dejager L, Libert C. Tumor necrosis factor alpha mediates the lethal hepatotoxic effects of poly(I: C) in-galactosamine-sensitized mice［J］. Cytokine, 2008, 42(1):55-61.
［6］Szabo G， Mandrekar P， Dolganiuc A． Innate immune respons and hepatic inflammation［J］． Semin Liver Dis, 2007, 27(4): 339-350．
［7］Wu Z， Han M， Chen T， et al． Acute liver failure: mechanisms of immune-mediated liver injury［J］. Liver Int, 2010, 30(6): 782-794.
［8］Zhao E， Ghulam I， Lin Y， et al． A Novel Oral Form of Pentamidine (OCZ103) Blocks TNF-α Mediated Mouse Liver Injury from GalN/LPS［C］． Boston Massachusetts:AASLD， 2014.
［9］Wu Z, Kong X, Zhang T, et al． Pseudoephedrine /ephedrine shows potent anti-inflammatory activity against TNF-α-mediated acute liver failure induced by lipopolysaccharide/ D-galactosamine［J］. Eur J Pharmacol, 2014, 724: 112-121.
［10］卢明芹,许烂漫,陈永平，等．内毒素耐受对D－GalN/LPS致大鼠肝损伤保护［J］．中国公共卫生, 2008, 24(12):1493-1494．
［11］Diehl AM． Cytokine regulation of liver injury and repair［J］． Immunol Rev, 2000， 174: 160-171．
［12］Soares JB， Pimentel-Nunes P， Roncon-A1buquerque R， et al． The role of 1ipopolysaccharide/ toll-like receptor 4 signaling in chronic liver diseases［J］. Hepatol Int, 2010, 4(4):659-672．
［13］Lu YC, Yeh WC, Ohashi PS. LPS/TLR4 signal transduction pathway［J］. Cytokine, 2008, 42(2):145-151.
［14］Ohuchida K， Mizumoto K， Lin C， et al． MicroRNA-10a is overexpressed in human pancreatic cancer and involved in its invasiveness partially via suppression of the HOXA1 gene［J］． Ann Surg Oncol, 2012, 19(7): 2394-2402.
［15］Ishizuka F， Shimazawa M, Inoue Y， et al. Toll-like receptor 4 mediates retinal ischemia/ reperfusion injury through nuclear factor kappaB and spleen tyrosine kinase activation［J］. Invest Ophthalmol Vis Sci, 2013, 54(8):5807-5816． |
|
|
|
Address: 1 North 2nd Street,
Zhongguancun, 
