灵芝酸A对D-氨基半乳糖/脂多糖诱导小鼠肝损伤的保护作用

卫昊; 张新玥

灵芝酸A对D-氨基半乳糖/脂多糖诱导小鼠肝损伤的保护作用

卫昊,
张新玥

陕西中医药大学药学院，陕西咸阳 712046

计量
- 文章访问数: 818
- HTML全文浏览量: 49
- PDF下载量: 477
- 被引次数: 0
出版历程
- 刊出日期: 2019-07-10

Protective Effect of Ganoderic Acid A on Hepatic Injury Induced by D-GalN/LPS in Mice

摘要

摘要: 目的研究灵芝酸A对D-氨基半乳糖(D-GaIN)/脂多糖(LPS)诱导小鼠肝损伤的保护作用及其相关机制。方法 60只C57BL/6小鼠随机分为4组：正常组、模型组、灵芝酸A低剂量组（20 mg/kg）、灵芝酸A高剂量组（40 mg/kg）。除正常组和模型组给予等体积蒸馏水外，其余各组每天灌胃给予相应剂量药物，共7 d。末次给药4 h后，腹腔注射D-GalN(700 mg/kg)与LPS(1 mg/kg)，正常组腹腔注射等体积溶媒。24 h后取血、肝脏。ELISA法检测血清谷草转氨酶（AST）、谷丙转氨酶（ALT）活性以及白介素（IL-6、IL-1β）和肿瘤坏死因子-α（TNF-α）含量，各组小鼠肝脏做HE染色，并采用蛋白免疫印迹法（Western blot）检测肝脏组织中NLRP3/NF-κB蛋白表达。结果灵芝酸A（20、40 mg/kg）能显著降低D-GaIN/LPS诱导的肝损伤小鼠血清ALT、AST活性及IL-6、IL-1β和TNF-α含量；能显著改善小鼠肝组织的病理学改变；显著降低肝脏NLRP3/NF-κB蛋白表达。结论灵芝酸A对D-GaIN/LPS诱导的小鼠肝损伤具有保护作用，这种效应可能与调控NLRP3/NF-κB信号通路有关。
- 灵芝酸A /
- 肝损伤 /
- NLRP3/NF-κB通路
Abstract: OBJECTIVE To observe the effect of ganoderic acid A (GA) on D-GalN/LPS induced liver injury in mice. METHODS 60 male C57BL/6 mice were randomly divided into 4 groups: normal control group， D-GalN/LPS group， D-GalN/LPS+ GA (20 mg/kg) group， D-GalN/LPS+GA (40 mg/kg) group. Mice in the normal control group and D-GalN/LPS group were given distilled water while other groups were given drugs for 7 d by gavage. After the last dose of 4 h， D-GalN (700 mg/kg) and LPS (1 mg/kg) were given by intraperitoneal injection， and the mice in normal control group were given same volume of vegetable oil solution. 24 h after established model， the blood and liver were collected. Aspartate aminotransaminase（AST），alanine aminotransaminase（ALT），interleukin-6 (IL-6)， interleukin-1β (IL-1β) and tumor necrosis factor (TNF-α) were measured by corresponding kits. Hematoxylin (HE) staining was used to observe the changes of hepatic histopathology.Western blotting was used to demonstrate the expression levels of related protein. RESULTS GA significantly reduced levels of AST，ALT，IL-6， IL-1β and TNF-α in serum. In addition， GA regulated proteins levels of NLRP3/NF-κB pathway in liver. CONCLUSION GA shows the therapeutical effect on D-GalN/LPS induced liver injury in mice which may be related to the regulation of NLRP3/NF-κB pathway.
- ganoderic acid A /
- liver injury /
- NLRP3/NF-κB pathway

HTML全文

参考文献(14)

[1]	HOOFNAGLE JH， CARITHERS RL JR， SHAPIRO C， et al. Fulminant hepatic failure: Summary of a workshop[J]. Hepatology， 1995， 21(1):240-252.
[2]	NAKAMA T， HIRONO S， MORIUCHI A， et al. Etoposide prevents apoptosis in mouse liver with D-galactosamine/lipopolysaccharide-induced fulminant hepatic failure resulting in reduction of lethality[J]. Hepatology， 2001， 33(6): 1441-1450.
[3]	KUHLA A， EIPEL C， SIEBERT N， et al. Hepatocellular apoptosis is mediated by TNFalpha-dependent Fas/FasLigand cytotoxicity in a murine model of acute liver failure[J]. Apoptosis， 2008， 13(12):1427-1438.
[4]	EIPEL C， KIDESS E， ABSHAGEN K， et al. Antileukoproteinase protects against hepatic inflammation， but not apoptosis in the response of D-galactosamine-sensitized mice to lipopolysaccharide[J]. Brit J Pharmacol， 2007， 151：406-413.
[5]	SHAKIL AO， KRAMER D， MAZARIEGOS GV， et al. Acute liver failure: Clinical features， outcome analysis， and applicability of prognostic criteria[J]. Liver Transplant， 2000， 6(2): 163-169.
[6]	LEE WM. Acute hepatic failure[J]. N Engl J Med， 1993， 329: 1862-1872.
[7]	MIGNON A， ROUQUET N， FABRE M， et al.LPS challenge in D-galactosamine-sensitized mice accounts for caspase-dependent fulminant hepatitis， not for septic shock[J]. Am J Respir Crit Care Med， 1999， 159: 1308-1315.
[8]	KAUFMAN RJ. Stress signaling from the lumen of the endoplasmic reticulum: Coordination of gene transcriptional and translational controls[J]. Genes Dev， 1999， 13(10): 1211-1233.
[9]	RON D， WALTER P. Signal integration in the endoplasmic reticulum unfolded protein response[J]. Nat Rev Mol Cell Biol， 2007， 8(7):519-529.
[10]	XU C， BAILLY MB， REED JC. Endoplasmic reticulum stress: Cell life and death decisions[J]. J Clin Invest， 2005， 115(10): 2656-2664.
[11]	RAO RV， ELLERBY HM， BREDESEN DE. Coupling endoplasmic reticulum stress to the cell death program[J]. Cell Death Differ， 2004， 11: 372-380.
[12]	NING ZW， LUO XY， WANG GZ， et al. MicroRNA-21 mediates Angiotensin Ⅱ-induced liver fibrosis by activating NLRP3 inflammasome/IL-1β axis via targeting Smad7 and Spry1[J]. Antioxid Redox Signal， 2016， 27(1):1-20.
[13]	WU X， ZHANG F， XIONG X， et al. Tetramethylpyrazine reduces inflammation in liver fibrosis and inhibits inflammatory cytokine expression in hepatic stellate cells by modulating NLRP3 inflammasome pathway[J]. IUBMB Life， 2015， 67(4):312-321.
[14]	SONG HM， LI X， LIU YY， et al. Carnosic acid protects mice from high-fat diet-induced NAFLD by regulating MARCKS[J]. Int J Mol Med， 2018， 42(1):193-207.