CAJ | 학술논문

目的明确脓毒症血小板表达Toll样受体4(TLR4)变化与血小板活化的关系及对预后的影响.方法前瞻、对照的临床试验设计.选天津市第一中心医院ICU 2008年5月至2009年12月收治的脓毒症患者64例,除外恶性肿瘤、免疫系统疾病、心肺复苏后、终末期肝或肾功能衰竭及入院24 h内死亡等患者.门诊查体健康志愿者15例为对照组,比较健康对照组和脓毒症组入院时和第3,5,9天外周静脉血血小板计数(PC)及参数(MPV,PDW)、血小板TLR4表达、血小板活化膜糖蛋白GPIⅠb/Ⅲa的PAC-1表达、血浆sCD40L及TNF-α浓度变化及关系;脓毒症组中分为血小板减少症即TCP组(至少1次低于150×109 L-1,27例)和非TCP组(37例),比较两组治疗前后(入院时及入院第9天)TLR4,PAC-1,sCD40L和TNF-α及APACHEⅡ评分、ICU住院时间、出血发生率以及28 d死亡率差异.基于时间测量组间数据比较采用可重复测量的单因素方差分析,两组间参数的比较采用独立样本t检验,计数资料进行x2检验.结果与健康对照组比较,脓毒症组PC减低(P=0.006),伴随MPV,PDW增大(P=0.046,P＜0.001);血小板FLR4及PAC-1表达同时上调(P＜0.001),且两种受体变化正相关;血浆中sCD40L和TNF-α浓度显著上升(P＜0.001).TCP组PAC-1表达、TNF-α浓度治疗前后均高于非TCP组(P=0.023,P=0.011);治疗后TCP组sCD40L、血小板TLR4表达显著高于非TCP组(P=0.047,P=0.001).TCP组比非TCP组出血发生率高(P=0.024)、ICU住院时间长(P=0.013)、APACHEⅡ评分高(P＜0.01)、28 d病死率高(P=0.048).结论脓毒症患者血小板TLR4表达上调及伴随的血小板活化与脓毒症血小板减少症发病密切相关,脓毒症并发TCP可能是预后不良标志.
목적 명학농독증혈소판표체Toll양수체4(TLR4)변화여혈소판활화적관계급대예후적영향.방법 전첨、대조적림상시험설계.선천진시제일중심의원ICU 2008년5월지2009년12월수치적농독증환자64례,제외악성종류、면역계통질병、심폐복소후、종말기간혹신공능쇠갈급입원24 h내사망등환자.문진사체건강지원자15례위대조조,비교건강대조조화농독증조입원시화제3,5,9천외주정맥혈혈소판계수(PC)급삼수(MPV,PDW)、혈소판TLR4표체、혈소판활화막당단백GPIⅠb/Ⅲa적PAC-1표체、혈장sCD40L급TNF-α농도변화급관계;농독증조중분위혈소판감소증즉TCP조(지소1차저우150×109 L-1,27례)화비TCP조(37례),비교량조치료전후(입원시급입원제9천)TLR4,PAC-1,sCD40L화TNF-α급APACHEⅡ평분、ICU주원시간、출혈발생솔이급28 d사망솔차이.기우시간측량조간수거비교채용가중복측량적단인소방차분석,량조간삼수적비교채용독립양본t검험,계수자료진행x2검험.결과 여건강대조조비교,농독증조PC감저(P=0.006),반수MPV,PDW증대(P=0.046,P＜0.001);혈소판FLR4급PAC-1표체동시상조(P＜0.001),차량충수체변화정상관;혈장중sCD40L화TNF-α농도현저상승(P＜0.001).TCP조PAC-1표체、TNF-α농도치료전후균고우비TCP조(P=0.023,P=0.011);치료후TCP조sCD40L、혈소판TLR4표체현저고우비TCP조(P=0.047,P=0.001).TCP조비비TCP조출혈발생솔고(P=0.024)、ICU주원시간장(P=0.013)、APACHEⅡ평분고(P＜0.01)、28 d병사솔고(P=0.048).결론 농독증환자혈소판TLR4표체상조급반수적혈소판활화여농독증혈소판감소증발병밀절상관,농독증병발TCP가능시예후불량표지.
Objective To unravel the relationship between Toll-like receptor 4 (TLR4) expression in platelets and the activation of platelet in thrombocytopenia (TCP) in case of sepsis. Method A total of 64 patients with sepsis were prospectively studied with control. Platelet count (PC), mean platelet volume (MPV),platelet distribution width (PDW),platelet TLR4 expression, platelet PAC-1 expression, sCD40L and TNF-α concentrations were compared between healthy control group (15 cases) and sepsis group on admission and 3 d,Sd,and 9 days after admission. The changes of MPV and PDW in TCP and non-TCP subgroups of sepsis before and after treatment were recorded. Prognostic index was analyzed. Results The PC was lower in sepsis group (P=0.006), and MPV and PDW were higher in sepsis group than those in healthy control group (P = 0.046, P =0.001). Platelet TLR4 and PAC-1 expressions, and sCD40L and TNF-α levels also increased more significantly in sepsis group (P ＜ 0.001). PAC-1 expression and TNF- level were higher in TCP group than those in non-TCP group before and after treatment (P = 0.023, P = 0.011). The sCD40L concentration and platelet TLR4 expression were significantly higher in treated TCP groups than in non-TCP group (P = 0.047, P = 0.001). Compared with non-TCP,the rate of bleeding was higher (P = 0.024) and the length of ICU stay was longer (P = 0.013).The APACHE Ⅱ score and the 28-day mortality were higher in TCP group (P ＜ 0.01, P = 0.048). Conclusions The elevation of platelet TLR4 expression in sepsis along with platelet activation is closely related to the incidence of thrombocytopenia. The occurrence of TCP is a poor prognosis sign of sepsis.