外源性一氧化碳分子对脓毒症时血小板膜糖蛋白过度表达和血小板活化的抑制作用及机制  

Inhibitive effect of carbon monoxide-releasing molecules 2 on the expression of glucoproteins and activation of platelets in sepsis

作　　者：孙炳伟[1] 仇雪枫[1] 王敏[1] 王波[1] 杨国涛[1] 孙艳[1] 陈曦[1] 

机构地区：[1]江苏大学附属医院烧伤整形科,江苏镇江212001

出　　处：《中华临床医师杂志（电子版）》2011年第12期3532-3537,共6页Chinese Journal of Clinicians(Electronic Edition)

基　　金：国家自然科学基金(30772256;81071546);江苏省自然科学基金面上项目(BK2008237);江苏省政府留学基金(2008-K002);江苏省"333工程"科研基金(2010-75)

摘　　要：目的探讨外源性一氧化碳释放分子(CORM-2)对脓毒症时血小板膜糖蛋白表达和血小板活化的抑制作用。方法将120只雄性BALB/c小鼠按随机数字表法分为正常对照组、盲肠结扎+穿孔术(CLP)组、CLP+无活性CORM-2(iCORM-2)组和CLP+CORM-2组。CLP+CORM-2组除伤后使用CORM-2外,其他处理同CLP组。于伤后6h、12h、24h分别检测小鼠血浆纤维蛋白原(FIB)、D-二聚体(D-D)的水平;全血电阻法检测血小板聚集功能;用流式细胞术检测血小板膜糖蛋白CD61和CD62p的表达水平;同时WesternBlot检测造血系细胞特异蛋白-1(HS1)分子磷酸化水平。结果与假手术组比较,12h、24hCLP组血浆FIB、D-D的水平明显增加[分别为(4.65±0.73)g/L,(5.76±0.88)g/L和(229.93±62.91)mg/L,(182.96±46.32)mg/L,P<0.01)],血小板聚集率明显增高,血小板膜糖蛋白CD61和CD62p的表达增加[分别为(94.87±11.22)%,(95.93±7.43)%和(34.81±4.76)%,(32.88±6.94)%,P<0.05)]。HS1分子磷酸化水平增加;CLP+CORM-2组血浆FIB、D-D的水平均显著降低[分别为(3.32±0.42)g/L,(3.68±0.46)g/L和(169.57±35.14)mg/L,(141.82±18.46)mg/L,P<0.05)],血小板聚集率下降明显,膜糖蛋白CD61和CD62p的表达也得到有效下调[分别为(72.12±11.67)%,(73.68±8.76)%和(21.38±1.61)%,(24.65±5.96)%,P<0.05],HS1分子磷酸化水平得到有效抑制。结论外源性CORM-2能明显下调脓毒症时血小板膜糖蛋白CD61和CD62p的表达以及HS1分子磷酸化水平,并抑制血浆FIB、D-D的升高,继而降低血小板黏附及聚集率,有效抑制脓毒症时血小板的过度活化。Objective To explore the inhibitive effects and potential mechanisms of carbon monoxide-releasing moleculesⅡon the activation of platelets in sepsis.Methods One hundred and twenty BALB/c male mice were randomly divided into sham,CLP,CLP +iCORM-2 and CLP +CORM-2(with 8 mg/kg CROM-2)group.The serum samples from each group were collected at 6 h,12 h and 24 h post CLP.The serum levels of FIB and D-D were examined.Expression of platelet glucoproteins(CD61、CD62p) in platelet-rich plasma were examined using flow cytometry.Platelet aggregation were examined using platelet-aggregation meter.Also,the phosphorylation levels of HS1 in platelets were examined.Results The serum levels of FIB and D-D[(4.65±0.73)g/L,(5.76±0.88)g/L and(229.93±62.91)mg/L,(182.96±46.32)mg/L],expression of CD61、CD62p [(94.87±11.22)%,(95.93±7.43)% and(34.81±4.76)%,(32.88±6.94)%] and platelet aggregations in CLP mice increased significantly(P<0.01,P<0.05).Compared with those of CLP group,the above index were decreased in CLP+CROM-2 group(P<0.05).In parallel,the phosphorylation levels of HS1 in platelets were significantly downregulated in CLP mice treated with CORM-2(P<0.05).Conclusions Taken together these findings indicate that CORM-released CO downregulates the expression of platelet glucoproteins and inhibits activation of HS1 pathway in sepsis.The ability of CORM to inhibit the phosphorylation of HS1 might be one underlying mechanism explaining its inhibition of platelets activation and efficacy in the treatment of sepsis.

关 键 词：脓毒症 一氧化碳 血小板 膜糖蛋白类 造血系细胞特异蛋白-1 

分 类 号：R459.7[医药卫生—急诊医学]