摘要
目的探讨异甘草酸镁对D-氨基半乳糖致急性肝衰竭(ALF)大鼠模型的保护作用及其机制。方法 90只SD大鼠随机分为正常组(A组,n=10)、模型组(B组,n=20)、异甘草酸镁低剂量组(C组,n=20)、中剂量组(D组,n=20)和高剂量组(E组,n=20)。A组腹腔内仅注射等量无菌生理盐水,其余4组均一次性腹腔注射10%D-氨基半乳糖。C、D、E 3组在造模30 min后均于尾静脉注射异甘草酸镁注射液(25、50和100 mg/kg)。建模24和48 h后分别取肝组织行HE染色观察肝组织结构的病理变化,收集血清检测各组大鼠肝功能指标[ALT、AST、TBil、白蛋白(Alb)]、促炎症因子[肿瘤坏死因子(TNF)α、白细胞介素(IL)1β、干扰素(IFN)γ]和抑炎症因子[IL-4、IL-10、转化生长因子(TGF)β]水平。计量资料多组间比较采用单因素方差分析,进一步两两比较采用SNK-q检验。结果 5组大鼠的血清ALT、AST、TBil和Alb水平比较差异均有统计学意义(F值分别为74.6、108.9、25.1、58.4,P值均<0.05);与A组比较,B组血清ALT、AST和TBil水平显著升高,Alb水平显著降低(P值均<0.05);与B组比较,C、D、E 3组ALT、AST、TBil水平显著降低,Alb水平上升,E组变化最明显,差异均有统计学意义(P值均<0.05)。5组大鼠的TNFα、IL-lβ、IFNγ、IL-4、IL-10、TGFβ水平比较差异均有统计学意义(F值分别为75.1、58.9、25.4、43.6、66.4、86.8,P值均<0.05);与A组比较,B组血清TNFα、IL-lβ、IFNγ、IL-4、IL-10、TGFβ水平显著升高,差异有统计学意义(P值均<0.05);与B组比较,C、D、E 3组血清TNFα、IL-1β、IFNγ水平显著降低,IL-4、IL-10、TGF-β水平显著升高,E组变化最明显,差异均有统计学意义(P值均<0.05)。结论异甘草酸镁可通过降低促炎因子、升高抗炎因子降低炎症反应,对ALF大鼠具有保护作用。
Objective To investigate the protective effect of magnesium isoglycyrrhizinate（ Mg IG） in rats with acute liver failure induced by D- galactosamine（ D- Gal N） and related mechanisms. Methods A total of 90 Sprague- Dawley rats were randomly divided into normal group（ group A,n = 10）,model group（ group B,n = 20）,low- dose Mg IG group（ group C,n = 20）,medium- dose Mg IG group（ group D,n = 20）,and high- dose Mg IG group（ group E,n = 20）. The rats in group A received intraperitoneal injection of the same volume of normal saline,and those in the other groups received single intraperitoneal injection of 10% D- Gal N. At 30 minutes after establishment of the model,the rats in groups C,D,and E received tail vein injection of Mg IG injection（ 25,50,and 100 mg / kg）. At 24 and 48 hours after establishment of the model,HE staining was performed to observe the pathological changes in the liver,and serum was collected to measure the levels of liver function parameters [alanine aminotransferase（ ALT）,aspartate aminotransferase（ AST）,total bilirubin（ TBil）,and albumin（ Alb） ],proinflammatory factors [tumor necrosis factor- α（ TNFα）,interleukin- 1β（ IL- 1β）,and interferon-γ（ IFNγ） ],and anti- inflammatory factors [interleukin 4（ IL- 4）,interleukin- 10（ IL- 10）,and transforming growth factor β（ TGFβ） ]in rats. The one- way analysis of variance was applied for comparison between multiple groups,and the Student- Newman-Keuls test was applied for comparison between any two groups. Results The serum levels of ALT,AST,TBil,and Alb showed significant differences across the five groups（ F = 74. 6,108. 9,25. 1,and 58. 4,all P 〈 0. 05）; compared with group A,group B had significant increases in the serum levels of ALT,AST,and TBil and a significant reduction in the serum level of Alb（ all P 〈 0. 05）; compared with group B,groups C,D,and E had significant reductions in the serum levels of ALT,AST,and TBil and a significant increase in the serum level of Alb,and these parameters showed the most significant changes in group E（ all P 〈 0. 05）. The serum levels of TNFα,IL- lβ,IFNγ,IL-4,IL- 10,and TGFβ showed significant differences across the five groups（ F = 75. 1,58. 9,25. 4,43. 6,66. 4,and 86. 8,all P 〈0. 05）; compared with group A,group B had significant increases in the serum levels of TNFα,IL- lβ,IFNγ,IL- 4,IL- 10,and TGFβ（ all P 〈 0. 05）; compared with group B,groups C,D,and E had significant reductions in the serum levels of TNFα,IL- lβ,and IFNγand significant increases in the serum levels of IL- 4,IL- 10,and TGFβ,and these parameters showed the most significant changes in group E（ all P 〈 0. 05）. Conclusion Mg IG can reduce inflammatory response through reducing proinflammatory factors and increasing anti- inflammatory factors,and thus exert protective effect on rats with ALF.
出处
《临床肝胆病杂志》
CAS
2016年第3期545-548,共4页
Journal of Clinical Hepatology
基金
中国肝炎防治基金会-天晴肝病研究基金课题(20120055)
江西省卫生厅中医药课题(1210452992)
