Effects Of Chronic Intermittent Hypoxia On The Expression Of CYP1A1 And CYP2J2 In Mouse Liver

objective: To study the effects of chronic intermittent hypoxia on liver structure,function and the expression of liver metabolism enzyme CYP450-1A1,CYP450-2J2 and transcription factor AP-1.Then to explore the relationship of the expression between AP-1 with CYP1A1 and CYP2J2 in mice with CIH.Methods: The 20 healthy male only six weeks of C57 BL mice were randomly divided into 2 groups with random number table method,followed by a blank control group(CTL group),a chronic intermittent hypoxia(CIH group),They would be conducted into an animal model for 16 weeks.After 16 weeks of molding,blood was taken from the heart and through high speed centrifugation to gain the serum to detect transaminase,protein and blood lipid concentration.The liver tissue was stained by HE and pathological changes were observed by optical microscope.RT-PCR detection method was used to detect m RNA expression of CYP1A1,CYP1A2,CYP2J2,CYP3A4,CYP2E1,Abcb1 a,CYP2A5,CYP2A25,CYP2C29 and CYP3A11 etc.Western blot method was used to detect the expression of CYP1A1,CYP2J2 and ap-1 protein.Results: 1.Expression of CYP1A1,CYP2J2 and AP-1:(1)Expression of CYP1A1:The expression of CYP1A1 in the liver tissue of the CIH group(0.7780±0.1247)was lower than that in the CTL group(1±0.00),and the difference was statistically significant(n=7,P=0.001<0.01).(2)Expression of CYP2J2: The expression of CYP2J2 of the CIH group(0.8697±0.0806)was lower than that in the CTL group(1±0.00),and the difference was statistically significant(n=7,P=0.001,<0.01).(3)Expression of AP-1:(1)The expression of C-FOS in CIH group(1.4107±0.2095)was higher than that in the CTL group(1±0.00),and the difference was statistically significant(n=6,P=0.001,<0.01).(2)The expression of C-JUN in the liver tissues of the mice in the CIH group(1.9678±0.6832)was higher than that in the CTL group(1±0.00),and the difference was statistically significant(n=6,P=0.006,<0.01).2.Correlation between AP-1 and the expression of CYP1A1 and CYP2J2 :(1)C-FOS was negatively correlated with CYP1A1,and the correlation coefficient was-0.917,which was statistically significant(n=6,P<0.01).C-JUN was negatively correlated with CYP1A1,and the correlation coefficient was-0.829,which was tatistically significant(n=6,P<0.05).(2)C-FOS was negatively correlated with CYP2J2,and the correlation coefficient was-0.864,which was statistically significant(n=6,P<0.05),C-JUN was negatively correlated with CYP2J2,and the correlation coefficient was-0.886,which was statistically significant(n=6,P <0.05).3.Liver structure and function:(1)transaminase: 1)Alanine transaminase:No statistical significance was found between the CTL group(33.4±9.52IU/L)and the CIH group(38.50±1.56IU/L),(n=8,P=0.948,>0.05);2)Aspartate transaminase: The results showed that the CIH group(197.25±106.51IU/L)was higher than the CTL group(98.9±31.27IU/L),and the difference was statistically significant(n=8,P=0.001,<0.05).(2)Blood fat: 1)Total cholesterol: there was no statistically significant difference between the CTL group(2.02±0.17mmol/L)and the CIH group(1.91±0.180 mmol/L)(n=8,P>0.05);2)Triglyceride: The CIH group(0.7±0.16mmol/L)was lower than the CTL group(0.53±0.092 mmol/L),and the difference was statistically significant(n=8,P=0.00,< 0.05).3)Low density lipoprotein: there was no significant difference between CIH group(0.3±0.18mmol/L)and CTL group(0.37±0.071mmol/L)(n=8,P=0.707,>0.05).4)High density lipoprotein: CIH group(1.89±0.25mmol/L)was lower than CTL group(2.15±0.17mmol/L),and the difference was statistically significant(n=8,P=0.01,<0.05).(3)protein: 1)Total protein: the CIH group(50.51±2.89g/L)was higher than the CTL group(46.09±2.52g/L),and the difference was statistically significant(n=8,P=0.004,<0.05).2)White protein: the CIH group(35.84±1.33g/L)was higher than the CTL group(33.24±2.22g/L),and the difference was statistically significant(n=8,P=0.012,<0.05).3)Globulin: There was no statistically significant difference between the CIH group(14.67±2.31g/L)and the CTL group(12.85±1.69g/L)(n=8,P=0.073,>0.05).Conclusions: 1 CIH lowered the expression of CYP1A1 and CYP2J2 in mice liver,while the ap-1 expression was up-regulated.2 The downregulation of CIH on the expression of CYP1A1 and CYP2J2 in mice 3 may be related to the up-regulation of ap-1 expression;4 The structure and function of mouse liver was damaged by CIH is relatively mild,and the liver tissue pathological change is most obvious in the centrilobular portion,while on the functional aspects,CIH can cause mouse liver lipid metabolic disorder,and the effect on HDL-C in the most significant,but not cause elevated serum transaminase levels in mice,also does not affect the protein synthesis function of liver.