학술논문
血小板活化相关因子和血栓前体蛋白在严重脓毒症中的表达 / Expression and clinical significance of platelet activating factor (PAC-1), CD629P and thrombus precursor protein (TpP) in severe sepsis
Document Type
Academic Journal
Author
耿平; 张劲松; 夏仲芳; 顾健; 徐敏; 徐继扬; 谈定玉; 解松刚; 沈连军; 马爱闻; GENG Ping; ZHANG Jin-song; XIA Zhong-fang; GU Jian; XU Min; XU Ji-yang; TAN Ding-yu; XIE Song-gang; SHEN Lian-jun; MA Ai-wen
Source
中华急诊医学杂志 / CHINESE JOURNAL OF EMERGENCY MEDICINE. 17(10):1080-1084
Subject
Language
Chinese
ISSN
1671-0282
Abstract
目的 探讨血小板活化相关因子(PAC-1、CD62P)和血栓前体蛋白(TpP)在严蘑脓毒症患者中的表达及其临床意义. 方法 前瞻性地选取2007年4月至2008年3月江苏省苏北人民医院急诊监护病房(EICU)收治的符合严重脓毒症诊断标准的患者入选严重脓毒症组(Ⅲ组).按照严重脓毒症治疗指南进行治疗,并根据28 d内是否存活分为生存亚组和死亡亚组,存在感染但未发生脓毒症同期患者设为一般感染组(Ⅱ组),同期门诊体检者或健康自愿者设为正常对照组(Ⅰ组).病例的选取均遵循随机的原则,三组的年龄、性别具有可比性;急性脑梗死、急性冠脉综合征、严重糖尿病和高脂血症者、恶性肿瘤、白血病、原发肝、肾、造血系统疾病者.长期卧床者、孕妇、近期使用过激素和免疫抑制剂者均除外.Ⅰ组和Ⅱ组均在入院第1天清晨空腹,Ⅲ组在入院第1、3,5天清晨空腹取外周静脉血,用酶联免疫吸附测定法(ELISA法)测定血栓前体蛋白(TpP),流式细胞术测定血小板膜糖蛋白(GP)Ⅱb/Ⅲ a复合物纤维蛋白原受体(PAC-1)、血小板颗粒膜糖蛋白140(CD62P),并对Ⅲ组进行Mar-shall评分.应用SPSS 12.0软件包处理数据,多组均数间比较采用方差分析,方差齐性检验采用Levene's法,方差齐性时采用LSD法,相关分析采用Bivariate法,以P<0.05为差异具有统计学意义. 结果 共有20例纳入Ⅰ组,20例纳入Ⅱ组,30例纳入Ⅲ组,其中生存亚组19例,死亡亚组11例.入院第1天,PAC-1、CD62P、TpP在Ⅰ组与Ⅱ组之间的表达差异无统计学意义(P>0.05),但Ⅰ组与Ⅲ组、Ⅱ组与Ⅲ组之间均差异具有统计学意义(P<0.05);PAC-1、CD62D、TpP在生存亚组的表达均随着病程显著下降而趋于正常,而在死亡亚组仍持续保持高值甚至显著升高,第1天时CD62P、TpP在亚组的表达差异无统计学意义(P>0.05),但在第3天时差异具有统计学意义,分别为(2.89±1.48)%vs.(5.04±2.57)%,P<0.01和(5.24±2.22)mg/L vs.(9.20±1.93)mg/L(P<0.01);而PAC-1在入院第1天亚组中的表达差异具有统计学意义(P<0.01),为(3.15±0.42)%vs.(5.30±0.48)%.两组的Marshall评分也呈类似变化,相关性分析显示:PAC-1、CD62P、TpP与Marshall评分呈明显正相关. 结论 严重脓毒症的早期就存在血小板活化和微血栓形成,两者共同参与了早期的高凝状态,在病情的发生发展过程中扮演了重要角色.动态监测CD62P和TpP有助于判断病情和预后,PAC-1具有危险分层效应,早期高表达者预后差,可尝试作为严重脓毒症的独立预警指标.
Objective To investigate the expression and clinical significance of platelet activating factor [PAC]-1, CD62P and TPP hi severe sepsis. Method Patients with severe sepsis who were admitted into the EICU of Subei People's Hospital from April 2007 to March 2008 were included. Patients with severe sepsis (Group Ⅲ)were treated according to the treatment guidelines for severe sepsis, and were divided, according to their clinical records, into those who survived and those who died within 28 days of admission. Patients admitted during the same period with symptoms of infection but without severe sepsis were included as the General Infected Group (Group Ⅱ). A Control Group (Group Ⅰ) comprised patients who visited the hospital over the same period for physical examination or the healthy volunteers. The group members were all included randomly, and the gender and sex of patients in all three groups were similar. Patients with acute brain infarction, acute coronary syndrome,serious diabetes, hyperlipidemia, malignant tumor, leukemia, primary liver, renal and hematopoietic system dis-eases,long-term bedridden patients, pregnant women, and patients taking hormone treatment or hranunosuppres-sants were excluded from the study. Morning venous blood was collected and ELISA and Flow Cytometry performed on the fwst day of admission for Groups Ⅰ- and Ⅱ, and on the first, third and fifth day after admission for Group Ⅲ, to determine the TpP,PAC-1 and CD62P respectively; and the Marshall score was determined. Data were ana-lyzed by SPSS 12.0 software. For continuous variables, comparisons among groups were analyzed by ANOVA.Levene's and LSD test were applied to assess homogeneity. Bivariate test is applied to Correlation Analysis. P<0.05 was regarded as a statistically significant difference. Results There were a total of 20 patients each in GroupⅠ-and GroupⅡ, and 30 in Group Ⅲ; of these, 19 were classed as survivors and 11 died during the 28-day peri-od. On the first day of admission, there were no significant differences in PAC-1, CD62P or TpP expression between Groups Ⅰ- and Ⅱ(P>0.05); however, Group Ⅲ was significantly different compared with both Group Ⅰ and Group Ⅱ (both:P<0.05). The expression of PAC-1, CD62P and TpP tended to decline in the survivor group,and became normal with the treatment process, while the expression of PAC-1 ,CD62P and TpP in the patients who died remained high, and even increased significantly over time. On the first day, the expression of CD62P and TpP in the patients who survived and in those who died was not significantly different (P>0.05); on the third day,however, a significant difference appeared with values of (2.89±1.48) % vs. (5.04±2.57) % (P<0.01) for CD62P, and (5.24±2.22) mg/L vs. (9.20±1.93) mg/L (P<0.01) for TpP. The expression of PAC-1 was significantly different between the two subgroups on the first day, with values of (3.15±0.42)% vs. (5.30±.48)% (P<0.01). The Marshall score of the two groups showed similar changes. Correlation analysis showed that PAC-1, CD62P and TpP were significantly correlated with the Marshall score. Conclusions Platelet activation and microthrombosis existing in the early stage of severe sepsis work together in the early hypercoagulable state.They both play important roles in disease development and progression. The dynamic detection of CD62P and TpP is beneficial to the diagnosis and prognosis of severe sepsis.PAC-1 appears to hold a risk stratification effect, as pa-tients with high expression of PAC-1 in the early stage show poor prognosis. Therefore, PAC-1 could be used as a marker of severe sepsis and poor prognsis.
Objective To investigate the expression and clinical significance of platelet activating factor [PAC]-1, CD62P and TPP hi severe sepsis. Method Patients with severe sepsis who were admitted into the EICU of Subei People's Hospital from April 2007 to March 2008 were included. Patients with severe sepsis (Group Ⅲ)were treated according to the treatment guidelines for severe sepsis, and were divided, according to their clinical records, into those who survived and those who died within 28 days of admission. Patients admitted during the same period with symptoms of infection but without severe sepsis were included as the General Infected Group (Group Ⅱ). A Control Group (Group Ⅰ) comprised patients who visited the hospital over the same period for physical examination or the healthy volunteers. The group members were all included randomly, and the gender and sex of patients in all three groups were similar. Patients with acute brain infarction, acute coronary syndrome,serious diabetes, hyperlipidemia, malignant tumor, leukemia, primary liver, renal and hematopoietic system dis-eases,long-term bedridden patients, pregnant women, and patients taking hormone treatment or hranunosuppres-sants were excluded from the study. Morning venous blood was collected and ELISA and Flow Cytometry performed on the fwst day of admission for Groups Ⅰ- and Ⅱ, and on the first, third and fifth day after admission for Group Ⅲ, to determine the TpP,PAC-1 and CD62P respectively; and the Marshall score was determined. Data were ana-lyzed by SPSS 12.0 software. For continuous variables, comparisons among groups were analyzed by ANOVA.Levene's and LSD test were applied to assess homogeneity. Bivariate test is applied to Correlation Analysis. P<0.05 was regarded as a statistically significant difference. Results There were a total of 20 patients each in GroupⅠ-and GroupⅡ, and 30 in Group Ⅲ; of these, 19 were classed as survivors and 11 died during the 28-day peri-od. On the first day of admission, there were no significant differences in PAC-1, CD62P or TpP expression between Groups Ⅰ- and Ⅱ(P>0.05); however, Group Ⅲ was significantly different compared with both Group Ⅰ and Group Ⅱ (both:P<0.05). The expression of PAC-1, CD62P and TpP tended to decline in the survivor group,and became normal with the treatment process, while the expression of PAC-1 ,CD62P and TpP in the patients who died remained high, and even increased significantly over time. On the first day, the expression of CD62P and TpP in the patients who survived and in those who died was not significantly different (P>0.05); on the third day,however, a significant difference appeared with values of (2.89±1.48) % vs. (5.04±2.57) % (P<0.01) for CD62P, and (5.24±2.22) mg/L vs. (9.20±1.93) mg/L (P<0.01) for TpP. The expression of PAC-1 was significantly different between the two subgroups on the first day, with values of (3.15±0.42)% vs. (5.30±.48)% (P<0.01). The Marshall score of the two groups showed similar changes. Correlation analysis showed that PAC-1, CD62P and TpP were significantly correlated with the Marshall score. Conclusions Platelet activation and microthrombosis existing in the early stage of severe sepsis work together in the early hypercoagulable state.They both play important roles in disease development and progression. The dynamic detection of CD62P and TpP is beneficial to the diagnosis and prognosis of severe sepsis.PAC-1 appears to hold a risk stratification effect, as pa-tients with high expression of PAC-1 in the early stage show poor prognosis. Therefore, PAC-1 could be used as a marker of severe sepsis and poor prognsis.