脓毒症患者血小板参数与Toll样受体4表达的关系及中西医结合治疗研究

目的 观察西药联合加味凉膈散对脓毒症患者血小板参数变化及活化状态与血小板Toll样受体4(TLR4)表达、炎症反应变化的影响.方法 64例脓毒症患者依据“不平衡指数最小的分配原则”随机分为西医常规治疗组(X组,32例)和西医联合加味凉隔散组(L组,32例),比较两组患者入院时及治疗3、5、9d的血小板计数(PLT)、平均血小板体积(MPV)、血小板分布宽度(PDW)、血小板TLR4阳性表达率、血小板膜糖蛋白GPⅡb/Ⅲa的半胱天冬酶原活化复合物-1(PAC-1)表位阳性表达率及血浆可溶性CD40配体(sCD40L)、肿瘤坏死因子-α(TNF-α)浓度变化,以及急性生理学与慢性健康状况评分系统Ⅱ(APACHE Ⅱ)评分、重症监护病房(ICU)住院时间、出血事件及28d病死率.以同期15例健康体检者作为对照组(C组).结果 与C组比较,脓毒症患者PLT(×109/L)显著降低(211.37±77.84比272.33±34.23,P＜0.01),MPV(fL)、PDW (fL)均显著增大(MPV:10.24土0.81比9.64±0.66;PDW:17.79±1.68比15.61±1.54,P＜0.05和P＜0.01),伴有血小板TLR4及PAC-1表达上调[TLR4:(39.93±9.07)%比(23.50±4.68)%,PAC-1:(42.21±8.74)%比(21.02±3.49)%,均P＜0.01],血浆中sCD40L (μg/L)和TNF-α(ng/L)浓度显著上升(sCD40L:6.94±1.05比3.27±0.41;TNF-α:60.10±9.77比4.08±3.08,均P＜0.01).治疗后9d,L组肝肾功能、TLR4和PAC-1表达及血浆sCD40L、TNF-α浓度较X组显著降低[肌酐(μmol/L):106.2±34.4比127.5±43.7;丙氨酸转氨酶(U/L):31.7±12.5比41.9±19.9;天冬氨酸转氨酶(U/L):54.1±21.6比68.5土24.1;TLR4:(27.14±6.08)%比(30.92±5.47)%;PAC-1:(27.52±6.51)%比(31.24±5.77)%;sCD40L:3.86±0.69比4.38土0.73; TNF-α:22.06±7.19比28.25±8.99,P＜0.05或P＜0.01],PLT(×109/L)较X组显著升高(261.93±55.32比231.37土63.58,P＜0.05).相关性分析显示:脓毒症患者血小板PAC-1表达与PLT呈负相关(r=-0.409,P＜0.01),与MPV、PDW、血小板TLR4表达、血浆sCD40L水平呈正相关(r1=0.262,r2=0.318,r3=0.341,r4=0.519,均P＜0.01);sCD40L与TNF-α呈正相关(r=0.542,P＜0.01).L组ICU住院时间(d)明显短于X组(8.06±2.86比9.31±2.48,P＜0.05),出血发生率低于X组(12.5%比21.9%,P＜0.05),9 d APACHEⅡ评分(分)显著低于X组(12.75±4.56比14.59±3.97,P＜0.05).L组与X组28 d病死率差异无统计学意义(15.63%比18.75%,P＞0.05).结论 脓毒症炎症反应常伴有血小板TLR4表达上调、血小板活化及PLT减少;西医联合加味凉膈散可通过下调血小板TLR4表达、减少血小板活化及炎症介质的释放,从而改善脓毒症患者血小板减少状态.

Platelet parameters and platelet Toll-like receptor 4 (TLR4) expression in patients with sepsis, and the effect of a joint treatment-plan integrating traditional Chinese and western medicine: a clinical study

Objective To examine the efficacy of a treatment regimen combining modern (Western) medication and a traditional Chinese medicinal recipe Modified Liang-Ge San(凉膈散) on sepsis,and its effect on platelet parameters/activation,platelet TLR4 expression and the intensity of inflammatory response in the patients.Methods 64 patients with sepsis were randomly assigned to two groups (32 each) to receive Western therapy only (group X) and Western therapy + Modified Liang-Ge San (group L).The values of:platelet count (PLT),mean platelet volume (MPV),platelet distribution width (PDW),the expression of TLR4 and procaspase activating compound-l (PAC-1) in platelets,plasma concentration of soluble CD40 ligand (sCD40L) and tumor necrosis factor-a (TNF-a) were collected on the day of admission,and 3,5,9 days after treatment.Acute physiology and chronic health evaluation Ic (APACHE Ⅱ ) score,length of stay in intensive care unit (ICU),bleeding events and 28 day mortality in these patients were also analyzed.A group of 15 healthy volunteers (group C) were used as control.Results Compared to group C,the patients with sepsis have significantly:lower PLT (X 109/L:211.37土 77.84 vs.272.33士 34.23,P 0.05).Conclusion In patients with sepsis,platelet TLR4 expression is elevated together with platelet activation.The joint application of Western medicine and Modified Liang-Ge San may suppress such up-regulation in TLR4/other inflammatory mediators,and alleviate platelet activation/thrombocytopenia in these patients.