Study On Serum Superoxide Dismutase In Patients With Chronic Hepatitis B And The Relationship With Interferon Receptor

Objective:We have previously demonstrated that there is an unbalance between oxidative stress and antioxidative defense in vivo of patients with chronic hepatitis B(CHB), leading to the progression of hepatitis B virus infecton.Superoxide anion radicals play a critical role in oxidative stress which has been implicated as a cause of hepatic fibrosis.Superoxide dismutase(SOD)has been reported to function as the front line enzyme of eliminating superoxide anion radicals in organism and of preventing organism oxidative stress from superoxide anion radicals.Thus the present study was performed and aimed to evaluate the change of serum superoxide dismutase in patients with chronic hepatitis B and investigate its mechanism in pathogenesis of chronic hepatitis B virus infection.Methods:The subjects were 66 patients with CHB,including 39 males and 27 females aged from 16 to 51 years old(average age 32.5±10.5 years),with no other exclusion criteria included coinfection with hepatitis C virus,hepatitis D virus or HIV;history of hepatocellular carcinoma(HCC);other causes of liver disease,including autoimmune hepatitis;Wilson's disease;haemochromatosis andα1-antitrypsin deficiency;serious medical or psychiatric illness.There are 10 age and gender matched healthy subjects who were enrolled in our study as the control group,5 males and 5 females(average age 29.7±5.8 years).All the subjects enrolled in our present study had no history of interference therapy with interferon,nucleoside analogue and immunomodulator in the later half a year.In the control and patient groups we measured serum SOD spectrophotometrically.Serum alanine aminotransferase(ALT),the virus load of HBVDNA in serum and liver tissue,the grade of liver pathology were also measured,and we detected the peripheral blood mononuclear cells interferonα-receptor2 mRNA(PBMCs IFNαR2 mRNA)using RT-PCR.We analyzed all the data statistically by SPSS 13.0.Results1.SOD levels decreased significantly in patients with CHB(55.821±12.664U/ml) compared with the control subjects(85.064±6.055U/ml)(P＜0.05).2.In patients group,the level of SOD presented a negative correlation with ALT(r= -0.541,P=0.000),it was also found that SOD was obviously lower in elevated ALT group(ALT≥40IU/L)than normal ALT(ALT＜40IU/L) group(49.616±4.662U/ml vs 54.112±5.225U/ml;P＜0.05).3.The correlation between serum SOD and the liver tissue pathology shows that high inflammation grade and severe fibrosis stage were significantly associated with a lower serum SOD level(r=-0.431,P=0.001;r=-0.304,P=0.013 respectively).4.There was not significant correlation between HBeAg and SOD(r=-0.255,P=0.103) and no significant difference of SOD between HBeAg positive and HBeAg negative subj ects(51.281±6.032U/ml vs 51.488±4.460U/ml;P＞0.05).,and also the activity of SOD was found of having no correlation with the load of HBVDNA in serum and liver tissue(r=0.126,P = 0.686;r=0.064,P=0.770).5.The positive expression rate of PBMCs IFNαR2 mRNA in patients group and control groups were 84.8%and 70%respectively,the expression level in patients group was higher than the controls group(0.54±0.43 vs 0.26±0.15,P=0.09),but there was found no statistical meaning.6.In patients group,the expression datum of PBMCs IFNαR2 mRNA in elevated ALT group and normal ALT group were 0.44±0.50,0.66±0.49,respectively.In normal ALT group the results exhibited that SOD was of a negative correlation with PBMCs IFNαR2 mRNA(r=-0.469,P=0.037).In elevated ALT group SOD level had no significant correlation with PBMCs IFNαR2 mRNA(r=-0.204, P=0.233)7.In patients group,the expression datum and of PBMCs IFNαR2 mRNA in HBeAg negative group and positive group were 0.67±0.53;0.39±0.25 respectively. PBMCs IFNαR2 mRNA had a negative correlation with serum SOD(r=-0.483, P=0.017).HBeAg positive group was found of no significant correlation between the two(r=0.043,P=0.816).ConclusionAs the single specialty enzyme for removing superoxide anion radicals,the level of SOD indicates the ability of antioxidant function in the body of Chronic Hepatitis B patients.There is a depressed-SOD which means a reduced-ability of antioxidant function and also a severe fibrosis in CHB patients.This may be an important mechanism of an aggravating state for CHB patients.Furthermore,a higher level of SOD could influence the expression of PBMCs IFNαR2 mRNA to a lower expression when it was in the immunotolerance period and in HBVDNA low replication period.