Role Of ERS In The Pathogenesis And Progression Of Hepatitis B

Objectives To analyze the expression level of endoplasmic reticulum stress(ERS)in peripheral blood and liver tissues of patients with viral hepatitis B,liver cirrhosis and liver cancer,and its relationship with cytokines and liver function,and to explore the role of ERS in the pathogenesis and progression of hepatitis B.To provide clinical basis for the diagnosis and treatment of hepatitis B,liver cirrhosis and liver cancer.Methods 136 patients were selected as the case group,including 90 patients with hepatitis B,36 patients with hepatitis B cirrhosis,10 patients with primary liver cancer,and 82 patients with non-HBV infection as control group.The markers of hepatitis B virus were quantitatively detected by immunoassay and the load of hepatitis B virus was detected by automatic fluorescent quantitative PCR analyzer.The liver function was detected by automatic biochemical analyzer,and the relative indexes of ERS in peripheral blood were detected by enzyme linked immunosorbent assay(ELISA)and the content of cytokine(TGF-?1?IL-10).The morphologic and pathological changes of liver tissue were observed by HE staining.Immunohistochemical method was used to detect the expression of ERS in liver tissue and Tunel method was used to detect the apoptosis of hepatocytes.SPSS 17.0 software was used for statistical analysis.The measurement data were expressed as mean �standard deviation((?)�s).The comparison between groups was based on single factor ANOVA,and the pairwise comparison was based on SNK Student-Newman-Keuls method(q test).Pearson test was used to analyze the correlation between measurement data,and the difference was statistically significant(P<0.05).Results 1 Comparison of age and gender between case group and control group: There was no statistically significant difference in age and gender between case group and control group.2 Liver function:The difference in liver function between the case group and the control group was statistically significant(P<0.05),ALT,AST,GLO increased with the severity of the disease,but it was the highest in the severe hepatitis B group,severe hepatitis B group was the lowest in ALB.3 HBV-DNA load:Except for the difference in logarithm of HBV-DNA load between the mild hepatitis B group and the moderate hepatitis B group(P<0.05),there was no significant difference between the other groups(P>0.05).4 Comparison of peripheral blood cytokines in different groups:The levels of cytokines in the case group were significantly different from those in the control group(P< 0.05).There was no significant difference between the two groups according to serum HBV-DNA load and hepatitis B virus serum marker(P>0.05).The levels of TGF-?1 in different clinical stages increased with the progression of the disease.The levels of IL-10 in mild hepatitis B group and severe hepatitis B group were higher than those in severe hepatitis B group.There was significant difference between liver cirrhosis group and liver cancer group(P<0.05).There was significant difference between moderate hepatitis B group and severe hepatitis B group and liver cancer group(P<0.05),but there was no significant difference between other groups(P>0.05).5 Comparison of ERS Indexes in different groups:The ERS index in the case group was higher than that in the control group(P<0.05).When the serum HBV-DNA load was different,the low GRP78 content in the study group was lower than the negative group,and the high copy group was lower than the medium copy group(P<0.05).There was no significant difference in the levels of CHOP and Caspase-12 between the two groups(P>0.05).There was no significant difference in serum markers of hepatitis B virus among the groups(P>0.05).GRP78 levels in the study group were different at different clinical stages.There was a statistically significant difference between the two groups(P<0.05).There was no significant difference in CHOP levels between the mild hepatitis B group and the moderate hepatitis B group,the severe hepatitis B group,and the hepatitis B cirrhosis group(P>0.05).There was no significant difference between the level of hepatitis B mild group,moderate hepatitis B group and severe hepatitis B group,hepatitis B cirrhosis group and liver cancer group(P>0.05).The level of ERS indicators was generally increased with the severity of illness.6 HE staining of liver tissue in different clinical stages showed that hepatocyte degeneration and necrosis were mild in mild hepatitis B group,obvious in moderate hepatitis B group,serious in severe hepatitis B group,and widespread necrosis in liver cirrhosis group.Heterogeneity of hepatocytes in patients with liver cancer.7 ERS related protein expression:There was no significant difference in GRP78 expression between mild and moderate hepatitis B patients(P>0.05).The level of GRP78 in liver cancer group was higher than that in liver cirrhosis group(P<0.05).There was no significant difference in CHOP level between mild hepatitis B group and moderate hepatitis B group(P>0.05),and it was lower than that in severe hepatitis B group.There was no significant difference between the severe hepatitis B group and the liver cirrhosis group(P>0.05),and the difference was lower than that in the liver cancer group(P<0.05).8 Hepatocyte apoptosis index(AI):The AI of liver cirrhosis group and liver cancer group was higher than that of mild hepatitis B group(P<0.05),while there was no significant difference in AI between liver cirrhosis group and liver cancer group(P>0.05).9 Correlation analysis:There was a positive correlation between GRP78/CHOP and TGF-?1,ALT,AST,GLO in patients with chronic hepatitis B(P<0.05),a negative correlation with ALB(P<0.05).There was a positive correlation between Caspase-12 and ALT,AST(P<0.05).There was no significant correlation between liver function index and logarithm of HBV-DNA load(P>0.05).Conclusions 1 The process of HBV infection involves the induction of hepatocyte apoptosis by ERS.2 ERS is closely related to the degree of liver inflammation.It is involved in the occurrence and development of hepatitis B.