巨噬细胞移动抑制因子与慢性乙型肝炎、乙型肝炎肝硬化的关系

目的 了解慢性乙型肝炎(乙肝)及乙肝肝硬化患者血清细胞因子巨噬细胞移动抑制因子(MIF)表达水平,探讨血清MIF水平与Ⅲ型前胶原肽(PⅢP)、组织金属蛋白酶抑制剂-1(TIMP-1)的相关性.方法 选择44例慢性乙肝患者(肝炎组)、44例乙肝肝硬化患者(肝硬化组)和30名健康者(对照组),取静脉血并应用ELISA方法检测其血清中细胞因子MIF浓度,分析实验组血清MIF水平与PⅢP、TIMP-1相关性.两组间均数比较采用t检验,MIF水平与ALT、AST、TBil、PTA、PⅢP及TIMP-1关系采用直线相关分析.结果 慢性乙肝组及肝硬化组血清MIF、PⅢP及TIMP-1的浓度比健康对照组升高.差异均有统计学意义(t=12.87、5.28、10.98,t=11.22、14.84、11.17)均P<0.05),但该3种细胞因子在慢性乙肝及肝硬化患者之间差异无统计学意义(t=-1.05、1.52、-2.07;均P>0.05);MIF水平与ALT、AST、TBil及PTA均无相关性;HBeAg阳性和高病毒载量(>1×105拷贝/mL)慢性乙肝患者体内MIF水平高于HBeAg阴性和低病毒载量(≤1×105拷贝/mL)患者.MIF水平与PⅢP水平在慢性乙肝组和肝硬化组中均存在正相关(r=0.603,P<0.05;r=0.415,P<0.05);MIF水平与TIMP-1水平在慢性乙肝组中存在正相关(r=0.458,P<0.05),而在肝硬化组无相关性(r=0.210,P>0.05),PⅢ P与TIMP-1在慢性乙肝组及肝硬化组均存在相关性(r=0.649,P<0.05)r=0.424,P<0.05).结论 慢性乙肝及肝硬化患者体内MIF水平明显升高,MIF的早期生成可能与病毒复制有关,与肝功能无关;MIF参与了肝炎,肝纤维化及肝硬化形成过程,可反应肝硬化程度.

The relationship between macrophage migration inhibitory factor and chronic hepatitis B and hepatitis B virus-related cirrhosis

Objective To investigate the level of serum macrophage migration inhibitory factor (MIF) and its correlation with serum precollagen Ⅲ peptide (PⅢP) and tissue inhibitor of metalloproteinase (TIMP)-1 in patients with chronic hepatitis B (CHB) and hepatitis B virus (HBV)-related cirrhosis. Methods Forty-four CHB patients (hepatitis B group), 44 patients with HBV-related cirrhosis (cirrhosis group) and 30 healthy controls (control group) were enrolled in this study. The venous blood was collected and MIF level was detected by enzyme-linked immunosorbent assay (ELISA). Correlations between MIF and PⅢP, TIMP-1 were analyzed in observed groups. Comparison between groups was done using t test. The correlations between MIF level and alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBil), plasma thromboplastin antecedent (PTA), PⅢP and TIMP-1 were analyzed by rectilinear correlation. Results The levels of serum MIF, PⅢP and TIMP-1 in CHB group and cirrhosis group were all significantly higher than those in control group (t=12.87,5.28, 10.98,t=11.22,14.84,11.17;all P<0.05), while there were no significant differences between CHB group and cirrhosis group (t= -1.05,1.52,--2.07;all P>0.05). There was no correlation between MIF level and ALT, AST, TBil and PTA. MIF level in CHB patients with hepatitis B e antigen (HBeAg) positive and high viral load were both higher than that in patients with HBeAg negative and low viral load. MIF level was both positively correlated with PⅢP level in CHB group and cirrhosis group (r=0. 603, P<0.05 and r=0. 415, P<0. 05, respectively). MIF level was also positively correlated with TIMP-1 level in CHB group (r=0. 458, P<0.05), while not correlated in cirrhosis group (r=0. 210, P>0.05). Levels of PⅢP and T1MP-1 were both correlated in CHB group and cirrhosis group (r=0. 849, P< 0.05 and r=0. 424, P<0.05, respectively). Conclusions The levels of serum MIF are significantly increased both in patients with CHB and cirrhosis. The early production of MIF might be related with viral replication, but not with liver function. MIF participates in formations of hepatitis, liver fibrosis and cirrhosis, which could reflect the degree of liver cirrhosis.