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.
Cox比例风险模型结果显示:在校正年龄、性别、HDL-C、TG、ALT、Hs-CRP、家庭收入、受教育程度后,CHS每增加1分,NAFLD的发病风险比为0.73(0.72~0.74)。CHS与NAFLD发病风险的剂量-反应关系,RCS结果表明(取25%、50%和75% 3个截点):CHS连续型变量与NAFLD呈非线性关系(P<0.05)。将CHS的不同分组代入模型,校正相同的混杂因素后,以Q1组为对照组,Q2组、Q3组、Q4组发生NAFLD的风险逐渐降低(P for trend<0.05),Q2组发病风险比为0.78(0.74~0.81),Q 3组发病风险比为0.57(0.54~0.59),Q4组发病风险比为0.38(0.36~0.41)。在男女性及年龄的分层分析中,也得到了类似的结果(P for trent<0.05)(表 2)。
表
2
心血管健康评分影响NAFLD发病的Cox风险比例模型
项目
例数
发病例数
发病率(/千人年)
HR(95%CI)
P值
总体
Q1组
10 057
4104
77.88
Q2组
17 732
5956
61.33
0.78(0.74~0.81)
<0.001
Q3组
10 321
2737
46.37
0.57(0.54~0.59)
<0.001
Q4组
12 401
2468
33.69
0.38(0.36~0.41)
<0.001
性别
<0.0011)
男
Q1组
9336
3655
73.94
Q2组
14 723
4492
54.84
0.77(0.73~0.80)
<0.001
Q3组
7492
1725
39.79
0.57(0.53~0.60)
<0.001
Q4组
6402
1097
28.92
0.52(0.39~0.45)
<0.001
女
Q1组
721
449
137.57
Q2组
3009
1464
96.32
0.79(0.71~0.88)
<0.001
Q3组
2829
1012
64.65
0.56(0.50~0.63)
<0.001
Q4组
5999
1371
38.81
0.37(0.33~0.42)
<0.001
年龄
<0.0011)
≤45岁
Q1组
3106
1164
67.79
Q2组
5584
1773
55.02
0.83(0.77~0.90)
<0.001
Q3组
3751
890
39.91
0.58(0.53~0.64)
<0.001
Q4组
6192
1016
27.14
0.37(0.34~0.41)
<0.001
>45岁
Q1组
6951
2940
82.75
Q2组
12 148
4183
64.46
0.76(0.72~0.79)
<0.001
Q3组
6570
1847
50.29
0.56(0.53~0.60)
<0.001
Q4组
6209
1452
40.54
0.42(0.39~0.45)
<0.001
注:模型校正了年龄、性别、HDL-C、TG、ALT、Hs-CRP、家庭收入、受教育程度。1)P for interaction<0.001。
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