The Dynamic Changes Of The Molecules Relative To Proliferatio Apoptosis And Metabolism In Acute Liver Injury Of Mice Induced By CCl₄

Objective To study the dynamic expression changes of the molecules relative to proliferation, apoptosis and metabolism in acute liver injury of mice induced by CCl₄ and the possible mechanism.Methods The acute liver injury of mice were induced by CCl₄(0.1% in olive oil, 0.1mL/10g) by abdominal injection. The enzyme activities of ALT and AST in serum were determined. Liver histopathological changes were observed at 3, 6, 12, 24, 30, 36, 42, 48, 54h after CCl₄ injection. The protein expression of PCNA, Bcl-2, Bax, CYP1A2, CYP2E1, CYP3A4, TNF-α, IL-6 and HSP70 were detected by Western blotting during the process. SPSS13.0 software was applied for the data statistics. Mean±SD and one-way ANOVA were used to compare these data. P value less than 0.05 was considered significant.Results Compared with the control mice, the enzyme activities of ALT and AST in the mice of liver injury were significantly increased (P<0.05) from 3h to 54h, and reached to the highest level at 36h. The livers'structures were all abnormal. At 36h, the liver injury reached to the highest level. The protein expression level of PCNA, Bcl-2, Bax, CYP1A2, CYP2E1, CYP3A4, TNF-α, IL-6 and HSP70 were significantly changed in the liver of mice during acute liver injury (P<0.05). The protein expression of PCNA were significantly decreased at 3,6,12,24h, increased after 30, peaked at 42h, then decreased gradually to the normal level till 54h. The protein expression of Bcl-2 were significantly decreased after CCl₄ injection. It decreased to the lowest levels at 24h. After 24h, the expression of Bcl-2 were increased but did not reached to the normal level. From 48h to 54h, it decreased again. The protein expression of Bax were significantly increased after CCl₄ injection and it increased to the highest levels at 12h. Then it decreased to the normal level gradually. The expression of CYP1A2 and CYP3A4 were significantly decreased at 3h after CCl₄ injection. After 3h, the expression of CYP1A2 and CYP3A4 were increased but did not reached to the normal level. From 48h to 54h, it decreased again. The protein expression of CYP2E1 were significantly increased from 3h to 12h. After that, the expression decreased to the lowest levels at 30h. Then it increased to the normal level gradually. The protein expression of HSP70 were significantly increased, peaked at 12h,reduced after 24h, then increased after 36h. The protein expression of IL-6 were significantly decreased, increased after 24h, peaked at 30h, then decreased gradually, but higher than the normal level at 54h.The protein expression of TNF-αwere significantly increased, peaked at 30h, reduced after 36h, but much higher than the normal level.Conclusion1. After CCl₄ administration, the enzyme activities of ALT and AST in the mice of liver injury are significantly increased; The livers'structures are all abnormal. At 36h, the enzyme activities of ALT and AST and the liver injury reach to the highest level, and liver histopathological changes are the most remarkable. The liver injury reach to the highest level.2. The protein expression level of PCNA, Bcl-2, Bax, CYP1A2, CYP2E1, CYP3A4, TNF-α, IL-6 and HSP70 are significantly changed in the liver of mice during acute liver injury. These factors may play important roles during acute liver injury.3. The isoenzyme (or analogue) of human CYP3A4 are found in the body of mice for the first time.