Graves’病病人外周血B细胞内PTEN表达及其意义  

EXPRESSION OF PTEN IN B CELLS IN THE PERIPHERAL BLOOD OF PATIENTS WITH GRAVES’DISEASE AND ITS SIGNIFICANCE

作　　者：蔚芳芳 谷钰峰 周瑾 王静[1] 崔孝敏 姚文杰 YU Fangfang;GU Yufeng;ZHOU Jin;WANG Jing;CUI Xiaomin;YAO Wengjie(School of Basic Medicine,Qingdao University,Qingdao 266071,China)

机构地区：[1]青岛大学基础医学院,山东青岛266071 [2]青岛大学附属烟台毓璜顶医院检验科 [3]青岛大学附属烟台毓璜顶医院内分泌科 [4]大连市第六人民医院影像科 [5]滨州医学院内分泌与代谢病学教研室

出　　处：《青岛大学学报（医学版）》2022年第1期100-104,共5页Journal of Qingdao University(Medical Sciences)

基　　金：国家自然科学基金资助项目(81700695)。

摘　　要：目的分析磷酸酶和张力蛋白同源物(PTEN)在Graves’病(GD)病人外周血B细胞中的表达,并探讨其在GD发生、发展中可能的机制。方法选取诊断明确的GD病人21例作为GD组,同期选取体检正常的健康人21例作为正常对照组(HC组)。采用流式细胞术检测两组外周血B细胞及其亚群PTEN的表达,并分析GD病人PTEN表达与促甲状腺激素(TSH)、游离甲状腺素(FT4)、游离三碘甲状腺原氨酸(FT3)、抗甲状腺过氧化物酶抗体(Anti-TPO)、抗甲状腺球蛋白抗体(TGAb)、促甲状腺素受体抗体(TRAb)等指标的相关性。采用实时荧光定量PCR(RT-PCR)方法检测两组外周血CD19^(+)B细胞PTEN mRNA的表达水平。结果与HC组相比较,GD组CD19^(+)B细胞的比例显著升高,CD19^(+)B细胞、幼稚性B细胞(CD19^(+)IgD^(+)CD27^(-))、未类型转换的记忆B细胞(CD19^(+)IgD+CD27+)、类型转换的记忆B细胞(CD19^(+)IgD-CD27+)、总的记忆细胞(CD19^(+)CD27+)以及双阴性B细胞(CD19^(+)IgD^(-)CD27^(-))PTEN表达明显升高,差异均有统计学意义(Z=-3.536~-2.252,P<0.05)。GD组CD19^(+)B细胞PTEN mRNA表达较HC组明显升高,差异有统计学意义(Z=-2.763,P<0.05)。相关性分析显示,PTEN与TRAb呈正相关(r=0.490,P<0.05)。结论PTEN在GD病人外周血B细胞中高表达,可抑制PI3K/AKT信号通路,使磷脂酰肌醇3磷酸(PIP3)水解为磷脂酰肌醇2磷酸(PIP2)增加,可能通过磷脂酶A2途径在GD中发挥生理学效应。Objective To analyze the expression of phosphatase and tensin homolog(PTEN)in B cells in the peripheral blood of patients with Graves’disease(GD),and to explore its possible mechanism of action in the development and progression of GD.Methods A total of 21 patients with a definite diagnosis of GD were enrolled in GD group,and 21 healthy subjects with normal physical examination results were concurrently enrolled in healthy control group(HC group).Flow cytometry was used to determine the expression of PTEN in B cells and their subsets in the peripheral blood of both groups,and analyses were performed on the correlation between PTEN expression and indices such as thyroid stimulating hormone,free thyroxine,free triiodothyronine,thyroid peroxidase antibody,thyroglobulin antibody,and thyrotropin receptor antibody(TRAb)in patients with GD.The mRNA expression of PTEN in CD19^(+)B cells in the peripheral blood was determined by quantitative real-time PCR.Results Compared with the HC group,the GD group had a significantly increased proportion of CD19^(+)B cells and significantly increased PTEN expression in CD19^(+)B cells,juvenile B cells(CD19^(+)IgD^(+)CD27^(-)),unswitched memory B cells(CD19^(+)IgD+CD27+),switched memory B cells(CD19^(+)IgD-CD27+),total memory cells(CD19^(+)CD27+),and double-negative B cells(CD19^(+)IgD^(-)CD27^(-))(Z=-3.536 to-2.252,P<0.05).The mRNA expression of PTEN in CD19^(+)B cells was significantly higher in the GD group than in the HC group(Z=-2.763,P<0.05).The correlation analysis indicated that PTEN was positively correlated with TRAb(r=0.490,P<0.05).Conclusion PTEN is highly expressed in B cells in the peripheral blood of patients with GD,which can inhibit the PI3K/Akt signaling pathway and increase the hydrolysis of phosphatidylinositol 3,4,5-triphosphate to phosphatidylinositol 4,5-bisphosphate and may exert physiological effects in GD through the phospholipase A2 pathway.

关 键 词：格雷夫斯病 B-淋巴细胞 PTEN磷酸水解酶 

分 类 号：R581.1[医药卫生—内分泌]