NAFLD患者外周血Srebp1c基因启动子甲基化表达水平
|
摘要
目的探讨非酒精性脂肪肝病(NAFLD)患者血浆固醇调节元件结合蛋白1c(Srebp1c)基因启动子甲基化状态。方法选择56名在西南医科大学附属医院消化内科确诊为NAFLD的患者,另选50名健康人群作为对照组。收集一般资料(年龄、性别、身高、体重)。收集两组人群静脉血,血脂和肝功能采用全自动血生化分析仪检测,qPCR检测基因水平表达,Srebp1c启动子甲基化水平采用甲基化特异性PCR检测。结果两组人群的年龄和性别差异均无统计学意义(P>0.05)。观察组体重、体重指数、总胆固醇、甘油三酯、低密度脂蛋白和谷丙转氨酶均高于对照组(t=9.103、3.749、4.550、5.363、2.889、9.783,P均<0.05);相对于对照组,观察组的Srebp1c表达上调(t=46.09,P<0.000 1);对照组和观察组的Srebp1c甲基化率分别为76.00%和19.64%,差异有统计学意义(χ~2=33.751,P<0.000 1)。结论 Srebp1c低甲基化可能在NAFLD患者的发病过程中扮演了重要角色。
Objective To investigate the methylation status of plasma Srebp1c gene promoter in patients with nonalcoholic fatty liver disease(NAFLD). Methods Fifty-six patients who were diagnosed with NAFLD in the Department of Gastroenterology,Southwestern Medical University Hospital were selected,and 50 healthy people were selected as the control group. General information(age,gender,height,weight)was collected. Venous blood was collected from both groups,and blood lipids and liver function were detected by an automatic blood biochemical analyzer. Srebp1c mRNA expression level was detected by q PCR. Srebp1c promoter methylation was detected by methylation-specific PCR. Results There were no significant differences in age and gender between the two groups(P>0.05). The body weight(t=9.103,P<0.000 1)and BMI(t=3.749,P=0.000 3)were higher in the observation group than in the control group. Total cholesterol(t=4.550,P<0.000 1),triglyceride(t=5.363,P<0.000 1)and low-density lipoprotein(t=2.889,P=0.004 4)levels of the observation group were higher than those of the control group. The observation group had higher alanine aminotransferase level than that of the control group(t=9.783,P<0.000 1). Compared with the control group,the expression of Srebp1c was up-regulated in the observation group(t=46.09,P<0.000 1);the methylation rate of Srebp1c promoter in the control group(76.00%)was significantly higher than that of the observation group(19.64%)(χ~2=33.751,P<0.000 1). Conclusion Srebp1c hypomethylation might play an important role in the pathogenesis of NAFLD patients.
Objective To investigate the methylation status of plasma Srebp1c gene promoter in patients with nonalcoholic fatty liver disease(NAFLD). Methods Fifty-six patients who were diagnosed with NAFLD in the Department of Gastroenterology,Southwestern Medical University Hospital were selected,and 50 healthy people were selected as the control group. General information(age,gender,height,weight)was collected. Venous blood was collected from both groups,and blood lipids and liver function were detected by an automatic blood biochemical analyzer. Srebp1c mRNA expression level was detected by q PCR. Srebp1c promoter methylation was detected by methylation-specific PCR. Results There were no significant differences in age and gender between the two groups(P>0.05). The body weight(t=9.103,P<0.000 1)and BMI(t=3.749,P=0.000 3)were higher in the observation group than in the control group. Total cholesterol(t=4.550,P<0.000 1),triglyceride(t=5.363,P<0.000 1)and low-density lipoprotein(t=2.889,P=0.004 4)levels of the observation group were higher than those of the control group. The observation group had higher alanine aminotransferase level than that of the control group(t=9.783,P<0.000 1). Compared with the control group,the expression of Srebp1c was up-regulated in the observation group(t=46.09,P<0.000 1);the methylation rate of Srebp1c promoter in the control group(76.00%)was significantly higher than that of the observation group(19.64%)(χ~2=33.751,P<0.000 1). Conclusion Srebp1c hypomethylation might play an important role in the pathogenesis of NAFLD patients.
引文
[1]BruzzìS,Sutti S,Giudici G,et al.B2-lymphocyte responses to oxidative stress-derived antigens contribute to the evolution of nonalcoholic fatty liver disease(NAFLD)[J].Free Radic Biol Med,2018,124:249-259.
[2]Younossi ZM,Koenig AB,Abdelatif D,et al.Global epidemiology of nonalcoholic fatty liver disease-Meta-analytic assessment of prevalence,incidence,and outcomes[J].Hepatology,2016,64(1):73-84.
[3]Loomba R,Sanyal AJ.The global NAFLD epidemic[J].Nat Rev Gastroenterol Hepatol,2013,10(11):686-690.
[4]张庆梅,薛萌,周宇,等.2型糖尿病男性患者血清总睾酮水平与非酒精性脂肪肝的相关性[J].中国热带医学,2017,17(11):1134-1137.Zhang QM,Xue M,Zhou Y,et al.Correlation between serum total testosterone levels and NAFLD in male T2DM patients[J].China Tropical Medicine,2017,17(11):1134-1137.
[5]陈湛勇,林捷胜,董洪利,等.膳食n-3多不饱和脂肪酸对非酒精性脂肪性肝病的影响[J].热带医学杂志,2018,18(3):307-310.Chen ZY,Lin JS,Dong HL,et al.The association of dietary intake of n-3 polyunsaturated fatty acids and non-alcoholic fatty liver disease[J].J Trop Med,2018,18(3):307-310.
[6]Chen H,Yuan R,Zhang Y,et al.ATF4 regulates SREBP1c expression to control fatty acids synthesis in 3T3-L1 adipocytes differentiation[J].Biochim Biophys Acta,2016,1859(11):1459-1469.
[7]Chen G,Yu D,Nian X,et al.LncRNA SRA promotes hepatic steatosis through repressing the expression of adipose triglyceride lipase(ATGL)[J].Sci Rep,2016,6:35531.
[8]Ha JH,Jang J,Chung SI,et al.AMPK and SREBP-1c mediate the anti-adipogenic effect ofβ-hydroxyisovalerylshikonin[J].Int J Mol Med,2016,37(3):816-824.
[9]吴文君,毕艳,汤孙寅炎,等.转录因子SREBP1c在高脂诱导L6细胞胰岛素抵抗中的作用及机制[J].中华医学杂志,2015,95(8):611-615.Wu WJ,Bi Y,Tang SYY,et al.Effects of transcription factor sterol regulatory element binding protein-1c in palmitate acidinduced L6 cells insulin resistance and its mechanism[J].Natl Med J China,2015,95(8):611-615.
[10]Hu MC,Kuro-o M,Moe OW.Renal and extrarenal actions of Klotho[J].Semin Nephrol,2013,33(2):118-129.
[11]Zhang Y,Liu Y,Chen L,et al.CRTC2 modulates hepatic SREBP1c cleavage by controlling Insig2a expression during fasting[J].Protein Cell,2018,9(8):729-732.
[12]侯洪涛,裘艳梅,张建,等.GLP-1下调非酒精性脂肪肝大鼠SOCS-3和SREBP-1c的表达[J].中国病理生理杂志,2016,32(7):1312-1316.Hou HT,Qiu YM,Zhang J,et al.GLP-1 down-regulates mRNAexpression of SOCS-3 and SREBP-1c in rats with nonalcoholic fatty liver disease[J].Chinese Journal of Pathophysiology,2016,32(7):1312-1316.
[13]Liu JJ,Liu S,Morgenthaler NG,et al.Association of plasma solubleα-klotho with pro-endothelin-1 in patients with type 2diabetes[J].Atherosclerosis,2014,233(2):415-418.
[14]Wu Y,Sarkissyan M,Vadgama JV.Epigenetics in breast and prostate cancer[J].Methods Mol Biol,2015,1238:425-466.
[15]Huang B,Jiang C,Zhang R.Epigenetics:the language of the cell[J].Epigenomics,2014,6(1):73-88.
[16]Milavetz BI,Balakrishnan L.Viral epigenetics[J].Methods Mol Biol,2015,1238:569-596.
[17]Covelo-Molares H,Bartosovic M,Vanacova S.RNA methylation in nuclear pre-mRNA processing[J].Wiley Interdiscip Rev RNA,2018:e1489.
[18]King GD,Rosene DL,Abraham CR.Promoter methylation and age-related downregulation of Klotho in rhesus monkey[J].Age(Dordr),2012,34(6):1405-1419.
[2]Younossi ZM,Koenig AB,Abdelatif D,et al.Global epidemiology of nonalcoholic fatty liver disease-Meta-analytic assessment of prevalence,incidence,and outcomes[J].Hepatology,2016,64(1):73-84.
[3]Loomba R,Sanyal AJ.The global NAFLD epidemic[J].Nat Rev Gastroenterol Hepatol,2013,10(11):686-690.
[4]张庆梅,薛萌,周宇,等.2型糖尿病男性患者血清总睾酮水平与非酒精性脂肪肝的相关性[J].中国热带医学,2017,17(11):1134-1137.Zhang QM,Xue M,Zhou Y,et al.Correlation between serum total testosterone levels and NAFLD in male T2DM patients[J].China Tropical Medicine,2017,17(11):1134-1137.
[5]陈湛勇,林捷胜,董洪利,等.膳食n-3多不饱和脂肪酸对非酒精性脂肪性肝病的影响[J].热带医学杂志,2018,18(3):307-310.Chen ZY,Lin JS,Dong HL,et al.The association of dietary intake of n-3 polyunsaturated fatty acids and non-alcoholic fatty liver disease[J].J Trop Med,2018,18(3):307-310.
[6]Chen H,Yuan R,Zhang Y,et al.ATF4 regulates SREBP1c expression to control fatty acids synthesis in 3T3-L1 adipocytes differentiation[J].Biochim Biophys Acta,2016,1859(11):1459-1469.
[7]Chen G,Yu D,Nian X,et al.LncRNA SRA promotes hepatic steatosis through repressing the expression of adipose triglyceride lipase(ATGL)[J].Sci Rep,2016,6:35531.
[8]Ha JH,Jang J,Chung SI,et al.AMPK and SREBP-1c mediate the anti-adipogenic effect ofβ-hydroxyisovalerylshikonin[J].Int J Mol Med,2016,37(3):816-824.
[9]吴文君,毕艳,汤孙寅炎,等.转录因子SREBP1c在高脂诱导L6细胞胰岛素抵抗中的作用及机制[J].中华医学杂志,2015,95(8):611-615.Wu WJ,Bi Y,Tang SYY,et al.Effects of transcription factor sterol regulatory element binding protein-1c in palmitate acidinduced L6 cells insulin resistance and its mechanism[J].Natl Med J China,2015,95(8):611-615.
[10]Hu MC,Kuro-o M,Moe OW.Renal and extrarenal actions of Klotho[J].Semin Nephrol,2013,33(2):118-129.
[11]Zhang Y,Liu Y,Chen L,et al.CRTC2 modulates hepatic SREBP1c cleavage by controlling Insig2a expression during fasting[J].Protein Cell,2018,9(8):729-732.
[12]侯洪涛,裘艳梅,张建,等.GLP-1下调非酒精性脂肪肝大鼠SOCS-3和SREBP-1c的表达[J].中国病理生理杂志,2016,32(7):1312-1316.Hou HT,Qiu YM,Zhang J,et al.GLP-1 down-regulates mRNAexpression of SOCS-3 and SREBP-1c in rats with nonalcoholic fatty liver disease[J].Chinese Journal of Pathophysiology,2016,32(7):1312-1316.
[13]Liu JJ,Liu S,Morgenthaler NG,et al.Association of plasma solubleα-klotho with pro-endothelin-1 in patients with type 2diabetes[J].Atherosclerosis,2014,233(2):415-418.
[14]Wu Y,Sarkissyan M,Vadgama JV.Epigenetics in breast and prostate cancer[J].Methods Mol Biol,2015,1238:425-466.
[15]Huang B,Jiang C,Zhang R.Epigenetics:the language of the cell[J].Epigenomics,2014,6(1):73-88.
[16]Milavetz BI,Balakrishnan L.Viral epigenetics[J].Methods Mol Biol,2015,1238:569-596.
[17]Covelo-Molares H,Bartosovic M,Vanacova S.RNA methylation in nuclear pre-mRNA processing[J].Wiley Interdiscip Rev RNA,2018:e1489.
[18]King GD,Rosene DL,Abraham CR.Promoter methylation and age-related downregulation of Klotho in rhesus monkey[J].Age(Dordr),2012,34(6):1405-1419.