Chung Tae-Wook, Kim Jeong-Ran, Suh Jeong-Il, Lee Young-Choon, Chang Young-Chae, Chung Tai Ho, Kim Cheorl-Ho
National Research Laboratory for Glycobiology, MOST and Departments of Biochemistry and Molecular Biology, College of Oriental Medicine, Dongguk University, Kyungju, Kyungbuk, Korea.
J Gastroenterol Hepatol. 2004 May;19(5):565-71. doi: 10.1111/j.1440-1746.2004.03344.x.
Matrix metalloproteases (MMP) and alpha-fetoproteins (AFP) are involved in hepatitis B virus (HBV)-induced chronic hepatitis. In the present study, we have determined the correlation between the MMP-9/MMP-9 ratio and AFP levels in the serum of patients during chronic viral B hepatitis.
Twenty-eight healthy individuals (18 men and 10 women) with a mean age of 36.3 years (range 23-58 years) and 50 patients (42 men, 8 women) with a mean age of 39.7 years (range 22-61 years) participated in the study. Forty-eight participants had HBV and the remaining two were either hepatitis G virus (HGV) or hepatitis C virus (HCV) carriers. Values of patients were compared with those obtained from 12 blood donor controls (5 men, 7 women), mean age 36 years (range 21-46 years). Patients' sera were subjected to examination of hepatitis B surface (HBs) and hepatitis B early (Hbe) antigen, SGOT, SGPT, AFP, MMP-2 and MMP-9. Serum levels of MMP-2 and MMP-9 activities were measured by a zymogram protease assay and densitometric measurement. The ratios of MMP-9 to MMP-2 were calculated by dividing the densitometric results.
Compared with the healthy controls, the mean serum concentrations of MMP-2 were slightly increased in the chronic HBV patients. In contrast, compared with the healthy controls, the mean serum concentrations of MMP-9 were significantly increased in the chronic HBV patients. When the ratios of the MMP-9/MMP-2 and amounts of the serum AFP were compared, a specific correlation between these two parameters was observed. Higher amounts of AFP were detected in the patients with a low ratio of MMP-9/MMP-2. Patients with hepatocellular carcinoma (HCC) and cirrhosis showed relatively low MMP-9/MMP-2 ratios in chronic hepatitis B. In addition, AFP levels of HCC and cirrhosis were higher than in chronic HBV patients.
These results indicate that the AFP level and ratio of MMP-9 and MMP-2 is highly correlated in chronic HBV-induced hepatitis. Because the serum MMP activities were significantly varied between each stage of AFP production in liver disease, an individual profile of these parameters might serve as an easy accessing serum marker to monitor the progression of liver disease.
基质金属蛋白酶(MMP)和甲胎蛋白(AFP)与乙型肝炎病毒(HBV)诱发的慢性肝炎有关。在本研究中,我们确定了慢性乙型病毒性肝炎患者血清中MMP-9/MMP-2比值与AFP水平之间的相关性。
28名健康个体(18名男性和10名女性)参与了研究,平均年龄为36.3岁(范围23 - 58岁);50名患者(42名男性,8名女性)也参与了研究,平均年龄为39.7岁(范围22 - 61岁)。48名参与者感染了HBV,其余两名是庚型肝炎病毒(HGV)或丙型肝炎病毒(HCV)携带者。将患者的值与12名献血者对照(5名男性,7名女性)的值进行比较,献血者平均年龄36岁(范围21 - 46岁)。对患者血清进行乙型肝炎表面(HBs)和乙型肝炎早期(Hbe)抗原、谷草转氨酶(SGOT)、谷丙转氨酶(SGPT)、AFP、MMP-2和MMP-9检测。通过酶谱蛋白酶分析和光密度测量来测定血清中MMP-2和MMP-9活性水平。MMP-9与MMP-2的比值通过光密度结果相除计算得出。
与健康对照组相比,慢性HBV患者血清中MMP-2的平均浓度略有升高。相比之下,与健康对照组相比,慢性HBV患者血清中MMP-9的平均浓度显著升高。当比较MMP-9/MMP-2比值和血清AFP量时,观察到这两个参数之间存在特定相关性。在MMP-9/MMP-2比值较低的患者中检测到较高水平的AFP。肝细胞癌(HCC)和肝硬化患者在慢性乙型肝炎中显示出相对较低的MMP-9/MMP-2比值。此外,HCC和肝硬化患者的AFP水平高于慢性HBV患者。
这些结果表明,在慢性HBV诱发的肝炎中,AFP水平与MMP-9和MMP-2的比值高度相关。由于在肝病AFP产生的各个阶段血清MMP活性存在显著差异,这些参数的个体特征可能作为一种易于获取的血清标志物来监测肝病的进展。