Foxo3a蛋白表达水平、Foxp3~+百分比与慢性乙型肝炎患者病情的相关性分析
|
摘要
目的:探讨Foxo3a蛋白表达水平、Foxp3~+百分比(CD4~+CD25~+Foxp3~+/CD4~+CD25~+)与慢性乙型肝炎(CHB)患者病情的相关性。方法:选择2013年1月至2016年1月四川省达州市中心医院感染内科收治的176例CHB患者为观察组,根据病情分为轻度组、中度组、重度组;并以同期的100例健康体检者为对照组。检测各组血清HBV-DNA病毒载量及血清谷丙转氨酶(ALT)、谷草转氨酶(AST)、总胆红素(TBil)水平,并检测外周血Foxp3~+百分比及Foxo3a蛋白的表达。采用Pearson相关性分析方法分析Foxo3a表达、Foxp3~+百分比与患者病情的相关性。结果:观察组HBV-DNA病毒载量,血清ALT、AST、TBil水平,CD4~+CD25~+Foxp3~+/CD4~+CD25~+和Foxo3a蛋白表达水平均显著高于对照组,且随着病情加重上述指标均显著升高(均P<0.05)。经Pearson相关性分析CD4~+CD25~+Foxp3~+/CD4~+CD25~+、Foxo3a蛋白分别与HBV、ALT、AST、TBil含量呈正相关关系(均P<0.05)。结论:Foxo3a蛋白表达、CD4~+CD25~+Foxp3~+/CD4~+CD25~+与CHB患者HBV感染及肝功能损害呈正相关关系,可作为临床检测指标。
Objective:To investigate the relationship between Foxo3 aexpression,Foxp3~+percentage(CD4~+CD25~+Foxp3~+/CD4~+CD25~+)and the severity of chronic hepatitis B(CHB).Methods:A total of 176 CHB patients from January 2013 to January 2016 in our hospital were selected(observation group)and divided into mild,moderate,and severe groups according to the severity of CHB.100 healthy subjects were selected as a control group.The serum HBV-DNA viral load,and the levels of alanine aminotransferase(ALT),aspartate aminotransferase(AST)and total bilirubin(TBil)were detected.The percentage of Foxp3~+and Foxo3 aprotein expression in PBMC were determined.Pearson correlation analysis was performed to evaluate the relationship between Foxp3~+,Foxo3 aand CHB.Results:The HBV-DNA viral load,the serum concentrations of ALT,AST and TBil as well as the percentage of Foxp3~+and Foxo3 aprotein expression level in the observation group were significantly higher than those in the control group,and were increased with the aggravation of CHB(P<0.05).The ratio of CD4~+CD25~+Foxp3~+/CD4~+CD25~+and Foxo3 aexpression were positively correlated with HBV-DNA,ALT,AST and TBil levels(P<0.05).Conclusion:The expression of Foxo3 aand Foxp3~+percentage were positively related to HBV infection and liver function damage in patients with CHB,which could be used as clinical indicators.
Objective:To investigate the relationship between Foxo3 aexpression,Foxp3~+percentage(CD4~+CD25~+Foxp3~+/CD4~+CD25~+)and the severity of chronic hepatitis B(CHB).Methods:A total of 176 CHB patients from January 2013 to January 2016 in our hospital were selected(observation group)and divided into mild,moderate,and severe groups according to the severity of CHB.100 healthy subjects were selected as a control group.The serum HBV-DNA viral load,and the levels of alanine aminotransferase(ALT),aspartate aminotransferase(AST)and total bilirubin(TBil)were detected.The percentage of Foxp3~+and Foxo3 aprotein expression in PBMC were determined.Pearson correlation analysis was performed to evaluate the relationship between Foxp3~+,Foxo3 aand CHB.Results:The HBV-DNA viral load,the serum concentrations of ALT,AST and TBil as well as the percentage of Foxp3~+and Foxo3 aprotein expression level in the observation group were significantly higher than those in the control group,and were increased with the aggravation of CHB(P<0.05).The ratio of CD4~+CD25~+Foxp3~+/CD4~+CD25~+and Foxo3 aexpression were positively correlated with HBV-DNA,ALT,AST and TBil levels(P<0.05).Conclusion:The expression of Foxo3 aand Foxp3~+percentage were positively related to HBV infection and liver function damage in patients with CHB,which could be used as clinical indicators.
引文
[1]史继静,常文仙,李元元,等.慢性乙型肝炎临床治疗的现状与挑战[J].科技导报,2016,34(20):34-39.
[2]PARK J J,WONG D K,WAHED A S,et al.HBV specific and global T cell dysfunction in chronic hepatitis B[J].Gastroenterology,2015,150(3):684-695.
[3]涂琛,游晶,刘怀鄂,等.乙型肝炎肝硬化患者辅助性T淋巴细胞17和调节性T淋巴细胞及维甲酸相关核孤儿受体γt和叉状头/翅膀状螺旋转录因子3mR-NA表达水平的变化及其临床意义研究[J].中国全科医学,2016,19(18):2130-2134.
[4]LIU W,LI J,CAI Y,et al.Hepatic IGF-1Roverexpression combined with the activation of GSK-3βand FOXO3ain the development of liver cirrhosis[J].Life Sci,2016,147(15):97-102.
[5]曹芬,陈竹,曾义岚,等.慢性乙型肝炎患者肝脏超声改变与肝损害的相关性研究[J].中国肝脏病杂志,2016,8(3):48-52.
[6]中华医学会肝病学分会,中华医学会感染病学分会.慢性乙型肝炎防治指南(2015年版)[J].中华实验和临床感染病病杂志,2015,9(5):570-589.
[7]BUSCH K,THIMME R.Natural history of chronic hepatitis B virus infection[J].Med Microbiol Immunol,2015,204(1):5-10.
[8]陈红英,丁洁,游晶.慢性乙型肝炎病毒感染者血清流行病学研究[J].中国全科医学,2017,20(8):939-947.
[9]娄鸣,游晶,刘怀鄂,等.慢性乙型肝炎病毒感染者外周血辅助性T淋巴细胞17和调节性T淋巴细胞的变化及二者平衡的研究[J].中国全科医学,2016,19(18):2115-2120.
[10]蒙达礼,苏明华,江建宁,等.慢性乙肝病毒携带者血清ALT、AST、HBV-DNA及HBVM与肝组织病理的关系[J].广西医科大学学报,2015,32(2):229-231.
[11]肖健,王登嵘,康迪,等.慢性HBV感染过程CD4+T细胞TLR2表达水平的研究[J].广西医科大学学报,2016,33(2):225-228.
[12]ROJAS J,TERAN-ANGEL G.Activation dependent mitochondrial translocation of Foxp3in human hepatocytes[J].Exp Cell Res,2016,343(2):159-167.
[13]程婷婷,王凤梅,朱争艳,等.HBV慢性感染者肝脏组织中CD4+T、CD8+T和FoxP3+Tregs细胞的表达水平[J].天津医科大学学报,2016,22(2):129-132.
[14]CAO W,QIU Z,ZHU T,et al.CD8+T cell responses specific for hepatitis B virus core protein in patients with chronic hepatitis B virus infection[J].J Clin Virol,2014,61(1):40-46.
[15]ZHAO X,PETURSSON F,VIOLLET B,et al.PGC-let and Foxo3amediate chondroprotection by AMP activated protein kinase[J].Arthritis Rheumatol,2014,66(1):3073-3082.
[16]WANG Y,TIAN H.miR-101suppresses HBV replication and expression by targeting FOXO1in hepatoma carcinoma cell lines[J].Biochem Bioph Resh Co,2017,487(1):167-172.
[17]唐海峰,朱素楠.苦参碱联合胸腺肽对慢性乙型肝炎患者血清Foxo3a、INF-α、HBV-DNA水平及T细胞亚群的影响[J].海南医学,2017,28(7):1055-1058.
[18]杨爱芳,张博佳,韦松华.慢性乙型肝炎患者Foxo3a表达水平对外周血CD8+T细胞凋亡的影响[J].国际流行病学传染病学杂志,2015,42(2):86-90.
[19]孙世仁.转录因子Fox O3a在乙肝病毒复制中的作用及机制研究[D].西安:第四军医大学,2009.
[20]胡园园,宁文锋.乙肝病毒表达与代谢的研究[J].中国现代医药杂志,2014,16(4):101-104.
[21]李学斌,谢庄,石放雄.FOXO蛋白在动物细胞的分化、增殖、免疫、衰老调节中的作用[J].中国临床康复,2006,10(9):158-162.
[2]PARK J J,WONG D K,WAHED A S,et al.HBV specific and global T cell dysfunction in chronic hepatitis B[J].Gastroenterology,2015,150(3):684-695.
[3]涂琛,游晶,刘怀鄂,等.乙型肝炎肝硬化患者辅助性T淋巴细胞17和调节性T淋巴细胞及维甲酸相关核孤儿受体γt和叉状头/翅膀状螺旋转录因子3mR-NA表达水平的变化及其临床意义研究[J].中国全科医学,2016,19(18):2130-2134.
[4]LIU W,LI J,CAI Y,et al.Hepatic IGF-1Roverexpression combined with the activation of GSK-3βand FOXO3ain the development of liver cirrhosis[J].Life Sci,2016,147(15):97-102.
[5]曹芬,陈竹,曾义岚,等.慢性乙型肝炎患者肝脏超声改变与肝损害的相关性研究[J].中国肝脏病杂志,2016,8(3):48-52.
[6]中华医学会肝病学分会,中华医学会感染病学分会.慢性乙型肝炎防治指南(2015年版)[J].中华实验和临床感染病病杂志,2015,9(5):570-589.
[7]BUSCH K,THIMME R.Natural history of chronic hepatitis B virus infection[J].Med Microbiol Immunol,2015,204(1):5-10.
[8]陈红英,丁洁,游晶.慢性乙型肝炎病毒感染者血清流行病学研究[J].中国全科医学,2017,20(8):939-947.
[9]娄鸣,游晶,刘怀鄂,等.慢性乙型肝炎病毒感染者外周血辅助性T淋巴细胞17和调节性T淋巴细胞的变化及二者平衡的研究[J].中国全科医学,2016,19(18):2115-2120.
[10]蒙达礼,苏明华,江建宁,等.慢性乙肝病毒携带者血清ALT、AST、HBV-DNA及HBVM与肝组织病理的关系[J].广西医科大学学报,2015,32(2):229-231.
[11]肖健,王登嵘,康迪,等.慢性HBV感染过程CD4+T细胞TLR2表达水平的研究[J].广西医科大学学报,2016,33(2):225-228.
[12]ROJAS J,TERAN-ANGEL G.Activation dependent mitochondrial translocation of Foxp3in human hepatocytes[J].Exp Cell Res,2016,343(2):159-167.
[13]程婷婷,王凤梅,朱争艳,等.HBV慢性感染者肝脏组织中CD4+T、CD8+T和FoxP3+Tregs细胞的表达水平[J].天津医科大学学报,2016,22(2):129-132.
[14]CAO W,QIU Z,ZHU T,et al.CD8+T cell responses specific for hepatitis B virus core protein in patients with chronic hepatitis B virus infection[J].J Clin Virol,2014,61(1):40-46.
[15]ZHAO X,PETURSSON F,VIOLLET B,et al.PGC-let and Foxo3amediate chondroprotection by AMP activated protein kinase[J].Arthritis Rheumatol,2014,66(1):3073-3082.
[16]WANG Y,TIAN H.miR-101suppresses HBV replication and expression by targeting FOXO1in hepatoma carcinoma cell lines[J].Biochem Bioph Resh Co,2017,487(1):167-172.
[17]唐海峰,朱素楠.苦参碱联合胸腺肽对慢性乙型肝炎患者血清Foxo3a、INF-α、HBV-DNA水平及T细胞亚群的影响[J].海南医学,2017,28(7):1055-1058.
[18]杨爱芳,张博佳,韦松华.慢性乙型肝炎患者Foxo3a表达水平对外周血CD8+T细胞凋亡的影响[J].国际流行病学传染病学杂志,2015,42(2):86-90.
[19]孙世仁.转录因子Fox O3a在乙肝病毒复制中的作用及机制研究[D].西安:第四军医大学,2009.
[20]胡园园,宁文锋.乙肝病毒表达与代谢的研究[J].中国现代医药杂志,2014,16(4):101-104.
[21]李学斌,谢庄,石放雄.FOXO蛋白在动物细胞的分化、增殖、免疫、衰老调节中的作用[J].中国临床康复,2006,10(9):158-162.