血浆细胞膜微粒改变与激素性股骨头缺血坏死的相关性研究
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摘要
研究背景及目的
长期使用或短期大量使用肾上腺上腺皮质类固醇激素(以下简称激素)可引起的股骨头无菌性缺血性坏死。尤其是2003年全球性SARS流行控制后,许多SARS患者康复后出现了激素应用的严重副作用—股骨头坏死。激素已公认为股骨头坏死的首要病因,其发病机理及防治措施日益为人所重视。
血浆膜微粒是循环中富含磷脂的亚微粒,它在凝血、细胞信号传导和细胞间的相互作用中,具有多种生物学活性,与血管功能异常、血栓形成和炎症密切相关。本研究通过血浆细胞膜微粒(micropaticles,MPs)检测,探讨微循环改变与激素性股骨头坏死的相关性。
资料与方法
采集24例激素性股骨头坏死患者(A组)及24例年龄、性别、种族匹配的健康志愿者(B组)的新鲜血;测定血浆凝血酶原时间(prothrombin time,PT)、国际标准化比值(international normalized ratio,INR)、活化部分凝血酶时间(activated partial thromboplastin time,APTT)和血浆纤维蛋白原(fibrinogen,FG);离心分离出乏血小板血浆;应用鼠抗人单克隆抗体PE-CD31、FITC-CD42b、FITC-CD45、FITC-CD51/61、PE-CD54、PEcy5-CD62E、FITC-CD105标定;流式细胞仪测定膜微粒的数量。
结果
两组凝血四项的平均秩次:PT(21.42vs27.58,P=0.126)、INR(22.23vs26.77,P=0.260)、APTT(21.90vs27.10,P=0.197),激素性股骨头坏死组均低于健康对照组;FG(27.35vs21.65,P=0.158),激素性股骨头坏死组高于健康对照组,两组差异无显著统计学意义。血浆细胞膜微粒的平均秩次,激素性股骨头坏死组均低于健康对照组;CD31~+MPs(18.40vs30.60,P=0.002)、CD31~+CD42b~+MPs(16.38vs32.63,P=0.000)、CD31~+CD45~+MPs(20.33vs28.67,P=0.020),差异具有显著统计学意义;CD42b~+MPs(21.83vs27.17,P=0.171)、CD45~+MPs(21.77vs27.23,P=0.107)、CD51/61~+MPs(21.65vs27.35,P=0.124)、CD54~+MPs(22.79vs26.21,P=0.397)、CD62E~+MPs(22.88vs26.13,P=0.421)、CD105~+MPs(22.79vs26.21,P=0.338)、CD54~+CD62E~+MPs(24.27vs24.73,P=0.910)、CD31~+CD105~+MPs(23.42vs25.58,P=0.450),差异无显著统计学意义。
结论
1、PT、INR、APTT和FG,虽然无显著统计学差异,但四项指标均提示:激素性股骨头坏死患者的血浆呈高凝倾向。
2、激素性股骨头坏死组所有MPs的平均秩次均低于健康对照组,部分具有显著统计学差异。提示糖皮质激素可抑制血浆细胞膜微粒形成和释放;细胞膜微粒代谢失衡可导致微循环障碍,与激素性股骨头坏死的发病机制密切相关。
创新点:激素性股骨头坏死是严重危害人类身心健康的疾患,其发病机制非常复杂。本研究在世界上首次提出通过检测人血浆中的膜微粒,用流式细胞仪确定膜微粒的来源,数量及判断体内的细胞状态。统计学分析得出其相关性。探讨该病的发生、发展机理,提高临床对该病的诊治水平。
Background and Objectives
Steroid-induced osteonecrosis of the femoral head(ONFH) is an aseptic and ischemic disease developing after steroid therapy by long-term use or high-dose given for short period.Especially,ONFH,the grave side-effect of steroid administration,occurred among many post-rehabilitation sufferers,after control of the global SARS prevalence in 2003.It is generally accepted that glucocorticosteroid is the first etio-factor for ONFH.However, the occurrence mechanism is unknown,and prevention methods and fundamental remedies remain to be established.It has been considered more and more intensively.
Microparticles are circulating,phospholipid rich,submicron particles. Investigation into their biological activity has revealed diverse actions in coagulation,cell signalling and cellular interactions.Abnormal levels of microparticles have been found in a number of conditions associated with vascular dysfunction,thrombosis and inflammation.To further explore the pathogenesis,we study the relationship between the alterations of cell-derived microparticles(MPs) and steroid-induced ONFH.
Materials and Methods
Plasma specimens from 24 patients with steroid-induced osteonecrosis of the femoral head(A group) and 24 age-,sex-and race-matched healthy controls(B group) were studied.Prothrombin time(PT),international normalized ratio(INR),fibrinogen(FG) and activated partial thromboplastin time(APTT) were analysed.Platelet-poor plasma was obtained by centrifugation.Plasma microparticles were labeled with monoclonal antibodies of PE-conjugated mouse anti-human CD31,CD54,and FITC-conjugated mouse anti-human CD42b,CD45,CD105,and PE-Cy5-conjugated mouse anti-human CD62E.Cell-derived microparticles were measured by three-colour flow cytometry.
Results
Mean ranks of PT(21.42vs27.58,P=0.126),INR(22.23vs26.77, P=0.260),APTT(21.90vs27.10,P=0.197),all above in patients with steroid-induced osteonecrosis of the femoral head were lower than in healthy controls,while FG(27.35vs21.65,P=0.158) was going in opposite direction, and there were no statistical significance between two groups.All mean ranks of cell-drived microparticles in patients with steroid-induced osteonecrosis of the femoral head were lower than in healthy controls.Among them,there were statistical significance between two groups in CD31~+MPs (18.40vs30.60,P=0.002),CD31~+CD42b~+MPs(16.38vs32.63,P=0.000), CD31~+ CD45~+MPs(20.33vs28.67,P=0.020),while there was no statistical significance in CD42b~+MPs(21.83vs27.17,P=0.171)、CD45~+MPs (21.77vs27.23,P=0.107 ),CD51/61~+MPs(21.65vs27.35,P=0.124), CD54~+MPs(22.79vs26.21,P=0.397 ),CD62E~+MPs(22.88vs26.13,P=0.421 ), CD105~+MPs(22.79vs26.21,P=0.338),CD54~+CD62E~+MPs(24.27vs24.73, P=0.910),CD31~+CD105~+MPs(23.42vs25.58,P=0.450).
Conclusions
1.Although there were no statistical significance between two groups in mean ranks of PT,INR,APTT and FG,all four clotting indexes uniformly suggested hypercoagulabale states in patients with steroid-induced osteonecrosis of the femoral head.
2.All mean ranks of cell-drived microparticles in patients with steroid-induced osteonecrosis of femoral head were lower than in healthy controls,and there were statistical significance among some of them between two groups.It suggests that glucocorticosteroids might inhibit or interfere the formation and release of microparticles.
3.It might be responsible for steroid-induced osteonecrosis of femoral head that the disequilibrium of microparticle metabolism could result in microcirculation disturbance.
长期使用或短期大量使用肾上腺上腺皮质类固醇激素(以下简称激素)可引起的股骨头无菌性缺血性坏死。尤其是2003年全球性SARS流行控制后,许多SARS患者康复后出现了激素应用的严重副作用—股骨头坏死。激素已公认为股骨头坏死的首要病因,其发病机理及防治措施日益为人所重视。
血浆膜微粒是循环中富含磷脂的亚微粒,它在凝血、细胞信号传导和细胞间的相互作用中,具有多种生物学活性,与血管功能异常、血栓形成和炎症密切相关。本研究通过血浆细胞膜微粒(micropaticles,MPs)检测,探讨微循环改变与激素性股骨头坏死的相关性。
资料与方法
采集24例激素性股骨头坏死患者(A组)及24例年龄、性别、种族匹配的健康志愿者(B组)的新鲜血;测定血浆凝血酶原时间(prothrombin time,PT)、国际标准化比值(international normalized ratio,INR)、活化部分凝血酶时间(activated partial thromboplastin time,APTT)和血浆纤维蛋白原(fibrinogen,FG);离心分离出乏血小板血浆;应用鼠抗人单克隆抗体PE-CD31、FITC-CD42b、FITC-CD45、FITC-CD51/61、PE-CD54、PEcy5-CD62E、FITC-CD105标定;流式细胞仪测定膜微粒的数量。
结果
两组凝血四项的平均秩次:PT(21.42vs27.58,P=0.126)、INR(22.23vs26.77,P=0.260)、APTT(21.90vs27.10,P=0.197),激素性股骨头坏死组均低于健康对照组;FG(27.35vs21.65,P=0.158),激素性股骨头坏死组高于健康对照组,两组差异无显著统计学意义。血浆细胞膜微粒的平均秩次,激素性股骨头坏死组均低于健康对照组;CD31~+MPs(18.40vs30.60,P=0.002)、CD31~+CD42b~+MPs(16.38vs32.63,P=0.000)、CD31~+CD45~+MPs(20.33vs28.67,P=0.020),差异具有显著统计学意义;CD42b~+MPs(21.83vs27.17,P=0.171)、CD45~+MPs(21.77vs27.23,P=0.107)、CD51/61~+MPs(21.65vs27.35,P=0.124)、CD54~+MPs(22.79vs26.21,P=0.397)、CD62E~+MPs(22.88vs26.13,P=0.421)、CD105~+MPs(22.79vs26.21,P=0.338)、CD54~+CD62E~+MPs(24.27vs24.73,P=0.910)、CD31~+CD105~+MPs(23.42vs25.58,P=0.450),差异无显著统计学意义。
结论
1、PT、INR、APTT和FG,虽然无显著统计学差异,但四项指标均提示:激素性股骨头坏死患者的血浆呈高凝倾向。
2、激素性股骨头坏死组所有MPs的平均秩次均低于健康对照组,部分具有显著统计学差异。提示糖皮质激素可抑制血浆细胞膜微粒形成和释放;细胞膜微粒代谢失衡可导致微循环障碍,与激素性股骨头坏死的发病机制密切相关。
创新点:激素性股骨头坏死是严重危害人类身心健康的疾患,其发病机制非常复杂。本研究在世界上首次提出通过检测人血浆中的膜微粒,用流式细胞仪确定膜微粒的来源,数量及判断体内的细胞状态。统计学分析得出其相关性。探讨该病的发生、发展机理,提高临床对该病的诊治水平。
Background and Objectives
Steroid-induced osteonecrosis of the femoral head(ONFH) is an aseptic and ischemic disease developing after steroid therapy by long-term use or high-dose given for short period.Especially,ONFH,the grave side-effect of steroid administration,occurred among many post-rehabilitation sufferers,after control of the global SARS prevalence in 2003.It is generally accepted that glucocorticosteroid is the first etio-factor for ONFH.However, the occurrence mechanism is unknown,and prevention methods and fundamental remedies remain to be established.It has been considered more and more intensively.
Microparticles are circulating,phospholipid rich,submicron particles. Investigation into their biological activity has revealed diverse actions in coagulation,cell signalling and cellular interactions.Abnormal levels of microparticles have been found in a number of conditions associated with vascular dysfunction,thrombosis and inflammation.To further explore the pathogenesis,we study the relationship between the alterations of cell-derived microparticles(MPs) and steroid-induced ONFH.
Materials and Methods
Plasma specimens from 24 patients with steroid-induced osteonecrosis of the femoral head(A group) and 24 age-,sex-and race-matched healthy controls(B group) were studied.Prothrombin time(PT),international normalized ratio(INR),fibrinogen(FG) and activated partial thromboplastin time(APTT) were analysed.Platelet-poor plasma was obtained by centrifugation.Plasma microparticles were labeled with monoclonal antibodies of PE-conjugated mouse anti-human CD31,CD54,and FITC-conjugated mouse anti-human CD42b,CD45,CD105,and PE-Cy5-conjugated mouse anti-human CD62E.Cell-derived microparticles were measured by three-colour flow cytometry.
Results
Mean ranks of PT(21.42vs27.58,P=0.126),INR(22.23vs26.77, P=0.260),APTT(21.90vs27.10,P=0.197),all above in patients with steroid-induced osteonecrosis of the femoral head were lower than in healthy controls,while FG(27.35vs21.65,P=0.158) was going in opposite direction, and there were no statistical significance between two groups.All mean ranks of cell-drived microparticles in patients with steroid-induced osteonecrosis of the femoral head were lower than in healthy controls.Among them,there were statistical significance between two groups in CD31~+MPs (18.40vs30.60,P=0.002),CD31~+CD42b~+MPs(16.38vs32.63,P=0.000), CD31~+ CD45~+MPs(20.33vs28.67,P=0.020),while there was no statistical significance in CD42b~+MPs(21.83vs27.17,P=0.171)、CD45~+MPs (21.77vs27.23,P=0.107 ),CD51/61~+MPs(21.65vs27.35,P=0.124), CD54~+MPs(22.79vs26.21,P=0.397 ),CD62E~+MPs(22.88vs26.13,P=0.421 ), CD105~+MPs(22.79vs26.21,P=0.338),CD54~+CD62E~+MPs(24.27vs24.73, P=0.910),CD31~+CD105~+MPs(23.42vs25.58,P=0.450).
Conclusions
1.Although there were no statistical significance between two groups in mean ranks of PT,INR,APTT and FG,all four clotting indexes uniformly suggested hypercoagulabale states in patients with steroid-induced osteonecrosis of the femoral head.
2.All mean ranks of cell-drived microparticles in patients with steroid-induced osteonecrosis of femoral head were lower than in healthy controls,and there were statistical significance among some of them between two groups.It suggests that glucocorticosteroids might inhibit or interfere the formation and release of microparticles.
3.It might be responsible for steroid-induced osteonecrosis of femoral head that the disequilibrium of microparticle metabolism could result in microcirculation disturbance.
引文
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