中华医学杂志
中華醫學雜誌
중화의학잡지
National Medical Journal of China
2014年
48期
3809-3812
,共4页
核糖体蛋白质S6激酶类%西罗莫司%血药浓度
覈糖體蛋白質S6激酶類%西囉莫司%血藥濃度
핵당체단백질S6격매류%서라막사%혈약농도
Ribosomal Protein S6 Kinases%Sirolimus%Trough level
目的 探讨应用流式磷酸化技术检测肝移植受体外周血CD3+细胞的mTOR通路下游P70S6激酶的磷酸化水平及价值.方法 选取自2008年10月至2013年10月首都医科大学附属北京朝阳医院肝移植患者84例,其中以西罗莫司为主要免疫抑制剂方案的26例(西罗莫司组),以他克莫司为主要免疫抑制剂方案的35例(他克莫司组),以环孢素A为主要免疫抑制剂方案的23例(环孢素A组).检测各组患者CD3+细胞P70S6激酶磷酸化水平,分析西罗莫司组P70S6激酶磷酸化水平与血药浓度的相关性.同时检测3例健康人P70S6激酸磷酸化程度的个体内差异和个体间差异.结果 健康人P70S6激酶磷酸化个体内差异的变异度范围为3.5％ ～ 5.6％,个体间差异变异度为18.9％ ～22.5％.西罗莫司组CD3+细胞P70S6激酶磷酸化(28.9±10.5)显著性低于健康对照组(57.2±8.4,P＜0.001),他克莫司组(42.5±14.1,P＜0.001)和环孢素A组(51.4±10.9,P＜0.00l).健康对照组的P70S6激酶活性(57.2±8.4)显著性高于他克莫司组(42.5±14.1,P＜0.01)和环孢素A组(51.4±10.9,P＜0.05).在西罗莫司组,P70S6激酶磷酸化与血药浓度无关(r=-0.18,P=0.39).结论 磷酸流式技术可以通过检测P70S6激酶磷酸化评估mTOR的抑制程度,检测P70S6激酶磷酸化水平可以为个性化免疫治疗提供更好的依据.
目的 探討應用流式燐痠化技術檢測肝移植受體外週血CD3+細胞的mTOR通路下遊P70S6激酶的燐痠化水平及價值.方法 選取自2008年10月至2013年10月首都醫科大學附屬北京朝暘醫院肝移植患者84例,其中以西囉莫司為主要免疫抑製劑方案的26例(西囉莫司組),以他剋莫司為主要免疫抑製劑方案的35例(他剋莫司組),以環孢素A為主要免疫抑製劑方案的23例(環孢素A組).檢測各組患者CD3+細胞P70S6激酶燐痠化水平,分析西囉莫司組P70S6激酶燐痠化水平與血藥濃度的相關性.同時檢測3例健康人P70S6激痠燐痠化程度的箇體內差異和箇體間差異.結果 健康人P70S6激酶燐痠化箇體內差異的變異度範圍為3.5％ ～ 5.6％,箇體間差異變異度為18.9％ ～22.5％.西囉莫司組CD3+細胞P70S6激酶燐痠化(28.9±10.5)顯著性低于健康對照組(57.2±8.4,P＜0.001),他剋莫司組(42.5±14.1,P＜0.001)和環孢素A組(51.4±10.9,P＜0.00l).健康對照組的P70S6激酶活性(57.2±8.4)顯著性高于他剋莫司組(42.5±14.1,P＜0.01)和環孢素A組(51.4±10.9,P＜0.05).在西囉莫司組,P70S6激酶燐痠化與血藥濃度無關(r=-0.18,P=0.39).結論 燐痠流式技術可以通過檢測P70S6激酶燐痠化評估mTOR的抑製程度,檢測P70S6激酶燐痠化水平可以為箇性化免疫治療提供更好的依據.
목적 탐토응용류식린산화기술검측간이식수체외주혈CD3+세포적mTOR통로하유P70S6격매적린산화수평급개치.방법 선취자2008년10월지2013년10월수도의과대학부속북경조양의원간이식환자84례,기중이서라막사위주요면역억제제방안적26례(서라막사조),이타극막사위주요면역억제제방안적35례(타극막사조),이배포소A위주요면역억제제방안적23례(배포소A조).검측각조환자CD3+세포P70S6격매린산화수평,분석서라막사조P70S6격매린산화수평여혈약농도적상관성.동시검측3례건강인P70S6격산린산화정도적개체내차이화개체간차이.결과 건강인P70S6격매린산화개체내차이적변이도범위위3.5％ ～ 5.6％,개체간차이변이도위18.9％ ～22.5％.서라막사조CD3+세포P70S6격매린산화(28.9±10.5)현저성저우건강대조조(57.2±8.4,P＜0.001),타극막사조(42.5±14.1,P＜0.001)화배포소A조(51.4±10.9,P＜0.00l).건강대조조적P70S6격매활성(57.2±8.4)현저성고우타극막사조(42.5±14.1,P＜0.01)화배포소A조(51.4±10.9,P＜0.05).재서라막사조,P70S6격매린산화여혈약농도무관(r=-0.18,P=0.39).결론 린산류식기술가이통과검측P70S6격매린산화평고mTOR적억제정도,검측P70S6격매린산화수평가이위개성화면역치료제공경호적의거.
Objective To explore the role of P70S6 kinase phosphorylation as a downstream of mammalian target of rapamycin (mTOR) pathway in CD3 positive cells of liver transplant patients.Methods A total of 84 liver transplant recipients were recruited from our hospital and divided into 3 treatment groups of sirolimus (n =26),tacrolimus (n =35) and cyclosporine (n =23).The P70S6 kinase phosphorylation of CD3 positive cell of patients and healthy control (HC) were analyzed by phospho-flow cytometry.A correlation analysis between P70S6 kinase phosphorylation and sirolimus trough level was performed.Intra-individual variability and inter-individual variability of P70S6 kinase phosphorylation were measured.Results The P70S6 kinase phosphorylation in HC showed a low degree of intra-individual variability (3.5％ to 5.6％) while the inter-individual variability between different healthy volunteers was higher (18.9％ to 22.5％).The P70S6 kinase phosphorylation in patients treated with sirolimus (28.9 ± 10.5) was significantly lower than in HC (57.2 ± 8.4,P ＜ 0.001),tacrolimus (42.5 ± 14.1,P ＜ 0.001) or cyclosporine treated ones (51.4 ± 10.9,P ＜ 0.001).The P70S6 kinase phosphorylation in HC (57.2 ± 8.4)was significantly higher than in tacrolimus (42.5 ± 14.1,P ＜ 0.01) or cyclosporine treated patients (51.4 ± 10.9,P ＜ 0.05).No correlation existed between P70S6 kinase phosphorylation and trough level of sirolimus (r =-0.18,P =0.39).Conclusion Phospho-flow cytometry assay has been established for determining the degree of mTOR inhibition by assessing P70S6 kinase phosphorylation.Quantification of P70S6 kinase phosphorylation may play an adjunct role in pharmacodynamically guiding an individualized mTOR inhibitor based immunosuppression.
