mTOR信号途径分子在再生障碍性贫血患儿T淋巴细胞中表达的意义
mTOR신호도경분자재재생장애성빈혈환인T림파세포중표체적의의
Expression and significance of mTOR signaling pathway in T cells in childhood aplastic anemia
  • 万方数据
    中华实用儿科临床杂志 중화실용인과림상잡지
    Journal of Applied Clinical Pediatrics
    2014年 15期 1166-1169 ,共4页

    孙豫兰%路丛%何广胜%朱明清%岑建农%展世宏%何海龙

    손예란%로총%하엄성%주명청%잠건농%전세굉%하해룡

    再生障碍性贫血%T淋巴细胞%mTOR%信号途径 再生障礙性貧血%T淋巴細胞%mTOR%信號途徑
    재생장애성빈혈%T림파세포%mTOR%신호도경
    Aplastic anemia%T cell%Mammalian target of rapamycin%Signaling pathway
    目的 通过检测再生障碍性贫血(AA)患儿T淋巴细胞内mTOR信号途径分子的表达水平,研究该信号途径在儿童AA中的改变.从T淋巴细胞的胞内信号转导途径上探讨儿童AA的免疫学发病机制.方法 用流式细胞仪(FCM)方法检测16例初治重型AA(SAA)(初治SAA组)及8例免疫抑制剂治疗有效的SAA患儿(SAA治疗有效组)外周血CD3+T淋巴细胞内mTOR信号途径分子磷酸化Akt (p-Akt)、磷酸化TSC2(p-TSC2)、磷酸化mTORC1(p-mTORC1)、磷酸化4EBP1(p-4EBP1)及磷酸化p70S6K(p-p70S6K)的表达水平,与17例健康儿童(健康对照组)及CEM细胞株(CEM组)的表达水平进行比较及分析.结果 1.初治SAA组外周血CD3+T淋巴细胞内p-Akt、p-TSC2、p-mTORC1、p-4EBP1及p-p70S6K表达水平均明显高于健康对照组(P＜0.05),而低于CEM组(P＜0.05),初治SAA组、健康对照组及CEM组p-Akt的平均荧光强度分别为8.04 ±3.78、2.59±1.01、20.23±8.98,p-TSC2分别为49.73±19.49、16.10±8.04、101.05±29.78,p-mTORC1分别为13.90 ±9.32、2.92±1.09、34.30±19.03,p-4EBP1分别为142.69±53.36、26.91±13.70、256.01±53.79,p-p70S6K分别为17.67±10.48、3.69 ±2.22、31.73±12.85.2.SAA治疗有效组外周血CD3+T淋巴细胞内p-Akt、p-TSC2、p-mTORC1、p-4EBP1及p-p70S6K的表达水平均低于初治SAA组(P均＜0.05);SAA治疗有效组p-Akt、p-TSC2、p-mTORC1、p70S6K的表达水平与健康对照组比较差异无统计学意义(P均＞0.05),但p-4EBP1的表达水平高于健康对照组(P＜0.05),治疗有效组信号途径分子的表达量依次为3.28±1.27、16.50±10.91、3.54±1.66、74.89±49.69、4.21 ±1.69.结论 1.初治SAA患儿外周血T淋巴细胞中p-Akt、p-TSC2、p-mTORC1、p-4EBP1、p-p70S6K表达升高,表明mTOR信号途径在SAA患儿中呈活化状态.2.SAA治疗有效患儿外周血T淋巴细胞中p-Akt、p-TSC2、p-mTORC1、p-4EBP1、p-p70S6K表达低于初治SAA患儿,mTOR信号途径的活化程度与疾病状态相关,说明该信号途径可能参与AA患儿T淋巴细胞的免疫异常.
    목적 통과검측재생장애성빈혈(AA)환인T림파세포내mTOR신호도경분자적표체수평,연구해신호도경재인동AA중적개변.종T림파세포적포내신호전도도경상탐토인동AA적면역학발병궤제.방법 용류식세포의(FCM)방법검측16례초치중형AA(SAA)(초치SAA조)급8례면역억제제치료유효적SAA환인(SAA치료유효조)외주혈CD3+T림파세포내mTOR신호도경분자린산화Akt (p-Akt)、린산화TSC2(p-TSC2)、린산화mTORC1(p-mTORC1)、린산화4EBP1(p-4EBP1)급린산화p70S6K(p-p70S6K)적표체수평,여17례건강인동(건강대조조)급CEM세포주(CEM조)적표체수평진행비교급분석.결과 1.초치SAA조외주혈CD3+T림파세포내p-Akt、p-TSC2、p-mTORC1、p-4EBP1급p-p70S6K표체수평균명현고우건강대조조(P＜0.05),이저우CEM조(P＜0.05),초치SAA조、건강대조조급CEM조p-Akt적평균형광강도분별위8.04 ±3.78、2.59±1.01、20.23±8.98,p-TSC2분별위49.73±19.49、16.10±8.04、101.05±29.78,p-mTORC1분별위13.90 ±9.32、2.92±1.09、34.30±19.03,p-4EBP1분별위142.69±53.36、26.91±13.70、256.01±53.79,p-p70S6K분별위17.67±10.48、3.69 ±2.22、31.73±12.85.2.SAA치료유효조외주혈CD3+T림파세포내p-Akt、p-TSC2、p-mTORC1、p-4EBP1급p-p70S6K적표체수평균저우초치SAA조(P균＜0.05);SAA치료유효조p-Akt、p-TSC2、p-mTORC1、p70S6K적표체수평여건강대조조비교차이무통계학의의(P균＞0.05),단p-4EBP1적표체수평고우건강대조조(P＜0.05),치료유효조신호도경분자적표체량의차위3.28±1.27、16.50±10.91、3.54±1.66、74.89±49.69、4.21 ±1.69.결론 1.초치SAA환인외주혈T림파세포중p-Akt、p-TSC2、p-mTORC1、p-4EBP1、p-p70S6K표체승고,표명mTOR신호도경재SAA환인중정활화상태.2.SAA치료유효환인외주혈T림파세포중p-Akt、p-TSC2、p-mTORC1、p-4EBP1、p-p70S6K표체저우초치SAA환인,mTOR신호도경적활화정도여질병상태상관,설명해신호도경가능삼여AA환인T림파세포적면역이상.
    Objective To sudy the changes in mTOR signaling pathway in childhood aplastic anemia(AA) by detecting the expression levels of the molecules of mTOR signaling pathway in T cells,and to explore immunologoical pathogenesis of AA in children from T cell intracellular signal transduction pathway.Methods Peripheral blood samples were collected from 16 newly diagnosed severe AA(SAA) patients and 8 patiens treated with effective immunosuppressive therapy,and the findings were compared with those of 17 healthy children (normal controls) and CEM cells (positive controls).The expressions of p-Akt,p-TSC2,p-mTORC1,p-4EBP1,p-p70S6K in CD3 + T cells in peripheral blood were detected by flow cytometry(FCM).Results 1.The expressions of p-Akt,p-TSC2,p-mTORC1,p-4EBP1,pp70S6K of the newly diagnosed SAA group were higher than those of the normal control group (P ＜ 0.05),but were lower than the postive control group (CEM group) (P ＜ 0.05).The mean fluorescence intensity (MFI) of p-Akt of three groups was 8.04 ± 3.78,2.59 ± 1.01 and 20.23 ± 8.98 respectively ;p-TSC2 was 49.73 ± 19.49,16.10 ± 8.04 and 101.05 ± 29.78 respectively ; p-mTOR was 13.90 ± 9.32,2.92 ± 1.09 and 34.3 ± 19.03 ;p-4EBP1 was 142.69 ± 53.36,26.91 ± 13.70,256.01 ± 53.79 ; p-p70S6 K were 17.67 ± 10.48,3.69 ± 2.22,31.73 ± 12.85 respectively.2.The expressions of p-Akt,p-TSC2,p-mTORC1,p-4EBP1,p-p70S6K of the effective treatment groups were lower than those of the newly diagnosed SAA group (P ＜ 0.05) ; the expressions of p-Akt,p-TSC2,p-mTORC1,p-p70S6K were similar to those of the normal control group(P ＞ 0.05),but the expressions of p-4EBP1 were higher(P ＜ 0.05).The MFI was followed by 3.28 ± 1.27,16.50 ± 10.91,3.54 ± 1.66,74.89 ± 49.69 and 4.21 ± 1.69.Conclusions 1.The expressions of p-Akt,p-TSC2,p-mTORC1,p-4EBP1,p-p70S6K were increased in the newly diagnosed SAA patients,the mTOR signaling pathway was activated in SAA patients.2.The expressions of p-Akt,p-TSC2,p-mTORC1,p4EBP1,p-p70S6K were lower than those of the newly diagnosed SAA patients.The degree of activation of mTOR signaling pathway was associated with disease status.The signaling pathways may be involved in the T cells of AA of the immune abnormalities.
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