牛牛游戏厅安卓,{原始关键词}

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                        2. 当前位置: 代写一篇论文多少钱 > 医学论文 > 血小板微囊泡对人微血管内皮细胞的作用机制

                          血小板微囊泡对人微血管内皮细胞的作用机制

                          时间:2020-04-30 10:56作者:潘丽娜 汪泽扬 陈丽媛
                          本文导读:这是一篇关于血小板微囊泡对人微血管内皮细胞的作用机制的文章,冠状动脉微血管疾病(coronary microvascular disease, CMD)是动脉内径<400 μm的微血管结构和功能异常所导致的冠状动脉疾病。在具有明显心肌缺血症状的冠脉非阻塞性病变患者中,CMD的发生率为45%~60%。

                            摘    要:牛牛游戏厅安卓,{原始关键词} 目的 探讨血小板微囊泡(platelet microvesicles, PMVs)对人微血管内皮细胞(human microvascular endothelial cells, HMECs)功能的影响。方法 取柠檬酸钠抗凝的健康人全血分离血小板,采用二磷酸腺苷(adenosine diphosphate, ADP)激活血小板产生PMVs,然后以不同浓度(10、20、50μg/mL)的PMVs作用于HMECs,并设立台式液作为空白对照组(control, Con组)和不含PMVs的上清组(supernatants, Sup组)。ELISA检测HMECs培养上清中血栓素A2(thromboxane A2, TXA2)和前列腺素I2(prostaglandin I2, PGI2)的稳定代谢产物TXB2和6-keto-PGF1α、细胞间黏附分子-1(intercellular adhesion molecule-1, ICAM-1)、血管细胞黏附分子-1(vascular cell adhesion molecule-1, VCAM-1)和E-选择素(E-selectin)的水平。Western blot检测HMECs中内皮素-1(endothelin-1, ET-1)和内皮型一氧化氮合酶(endothelial nitric oxide synthase, eNOS)的磷酸化水平。荧光探针检测HMECs中一氧化氮(nitric oxide, NO)含量。采用流式细胞仪定量检测HMECs培养上清中内皮微囊泡(endothelial microvesicles,EMVs)的含量。结果 与Con组和Sup组比较,PMVs可使HMECs培养上清TXB2的水平升高(P<0.05),6-keto-PGF1α的水平降低(P<0.05),均呈时间和剂量依赖性;PMVs可使HMECs中eNOS的磷酸化水平和NO含量显着下降,ET-1水平升高;经PMVs作用后,HMECs培养上清中ICAM-1、VCAM-1和E-selectin的表达水平亦显着升高(P<0.05)。与Con组和Sup组比较,50μg/mL PMVs作用于HMECs 24 h后,培养上清中EMVs的水平显着增加(P<0.05)。结论 PMVs可导致微血管内皮细胞的功能紊乱和损伤。这可能是血小板参与微循环功能障碍发生的重要机制之一。

                            关键词:牛牛游戏厅安卓,{原始关键词} 血小板微囊泡; 微血管内皮细胞; 血栓素A2; 内皮型一氧化氮合酶; 血管细胞黏附分子-1; 内皮微囊泡;

                            Abstract: Objective To investigate the effect of platelet microvesicles(PMVs) on the function of human microvascular endothelial cells(HMECs). Methods Blood samples from healthy volunteers were collected and anticoagulated with one-tenth volume of citrate solution to isolate platelet-rich plasma(PRP). PMVs released from adenosine diphosphate(ADP)-activated human platelets was collected by centrifugation. HMECs were cultured and grouped as following: Tyrode's buffer as control(Con) group, final concentration of PMVs at 10, 20, 50 μg/mL respectively, and supernatant(Sup) of PMVs(almost PMVs free) for 24 h. ELISA was used to detect the contents of thromboxane B2(TXB2) and 6-keto-PGF1α, the stable metabolites of TXA2 and prostaglandin I2(PGI2) respectively, intercellular adhesion molecule-1(ICAM-1), vascular cell adhesion molecule-1(VCAM-1) and E-selectin in the culture supernatant of HMECs. The expression of endothelin-1(ET-1) and endothelial nitric oxide synthase(eNOS) phosphorylation in HMECs were determined by Western blotting. Nitric oxide(NO) production in HMECs was measured by fluorescent probe. Endothelial microvesicles(EMVs) secreted by HMECs in the culture supernatant were determined by flow cytometry. Results Compared with Con group and Sup group, PMVs significantly upregulated the level of TXB2 and decreased that of 6-keto-PGF1α in the supernatant of HMECs in a time-and dose-dependent manner(P<0.05). After incubation with PMVs, the phosphorylated eNOS and the production of NO in HMECs were reduced, while the expression levels of ET-1, ICAM-1, VCAM-1 and E-selectin in the supernatant of HMECs were increased significantly(P<0.05). The concentration of EMVs induced by 50 μg/mL PMVs for 24 h was were increased obviously when compared with con group and Sup group(P<0.05). Conclusion PMVs may induce the to dysfunction and damage of microvascular endothelial cells. This might be one of the important mechanisms by which platelets are involved in microcirculation dysfunction.

                            Keyword: platelet microvesicles; human microvascular endothelial cells; thromboxane A2; endothelial nitric oxide synthase; vascular cell adhesion molecule-1; endothelial microvesicles;

                            冠状动脉微血管疾病(coronary microvascular disease, CMD)是动脉内径<400 μm的微血管结构和功能异常所导致的冠状动脉疾病。在具有明显心肌缺血症状的冠脉非阻塞性病变患者中,CMD的发生率为45%~60%[1]。糖尿病、高脂血症、高血压、心肌缺血再灌注损伤、吸烟和慢性炎症等因素均可导致CMD。微血管内皮细胞功能紊乱和结构改变是导致CMD发生的重要原因[2]。研究表明,心血管疾病的许多危险因素均可能引起微血管内皮细胞中一氧化氮(nitric oxide, NO)/内皮素-1(endothelin-1, ET-1)、血栓素A2(thromboxane A2, TXA2)/前列腺素I2(prostaglandin I2, PGI2)的比值失衡,出现微血管内皮功能紊乱和通透性增加,同时增加粒细胞在局部的浸润,可最终导致微血管闭塞,从而引发心肌缺血和心血管不良事件。因此,进一步探讨微血管内皮细胞功能障碍发生的机制对CMD的防治具有重要意义。
                           

                          血小板微囊泡对人微血管内皮细胞的作用机制
                           

                          牛牛游戏厅安卓,{原始关键词}   XUEXIAOBANHENEIPIXIBAOZHIJIANDEXIANGHUZUOYONGSUODAOZHIDEJUBUYANZHENGFANYINGSHINEIPIGONGNENGZHANGAIDEZHONGYAOYUANYINZHIYI[3]。DANGXUEGUANNEIPIXIBAOBEIJIHUOHUOSUNSHANGSHI,XUEXIAOBANKEKUAISUNIANFU、JUJIYUGAIBUWEI,SHIFANGDUOZHONGYANZHENGJIEZHIHEQUHUAYINZI,LIXIBAOTONGGUOYUJIHUODEXUEXIAOBANHENEIPIXIBAOZHIJIANDEXIANGHUZUOYONG,XUNSUJUJIZAISHOUSUNXUEGUANBUWEI,JINYIBUJIAZHONGYANZHENGFANYINGHESUNSHANG。CIWAI,BEIJIHUODEXUEXIAOBANKESHIFANGCHUDALIANGDEXUEXIAOBANWEINANGPAO(platelet microvesicles,PMVs),FAHUIGENGGUANGFANDECUYANZHENGHECUXUESHUANXINGCHENGZUOYONG[4]。PMVsSHIZHIJINGWEI0.1~1 μmDEMOXINGWEINANGPAO,YOUZHIZHISHUANGFENZICENG、XUEXIAOBANMODANBAIHENEIRONGWUSUOZUCHENG,HANYOUXIANLITI、microRNAsHEXIBAOYINZIDENGDUOZHONGSHENGWUHUOXINGWUZHI。PMVsYUXIBAOJIECHUHOUKETONGGUONEIYINHEMORONGHEDENGFANGSHIJIANGSHENGWUHUOXINGWUZHIDISONGJIBAXIBAO,SHIXIANDUIXIBAOGONGNENGDEDIAOKONG[5]。YIYOUYANJIUBIAOMING,ZAIJIXINGGUANMAIZONGHEZHENGHUANZHEXUEJIANGZHONG,PMVsSHUIPINGJIAOWENDINGXINGGUANXINBINGHUANZHEXIANZHESHENGGAO,QIEYUXINXUEGUANFENGXIANHEBULIANGLINCHUANGYUHOUCHENGZHENGXIANGGUAN。

                            BENKETIZUQIANQIYANJIUFAXIAN,PMVsJUYOUCUJINDONGMAIZHOUYANGYINGHUABANKUAIXINGCHENGHEXUEGUANXINSHENGDEZUOYONG[6,7],DANPMVsDUIWEIXUEGUANGONGNENGDEYINGXIANGSHANGBUQINGCHU。BENYANJIUCAIYONGERLINSUANXIANGAN (adenosine diphosphate,ADP)JIHUOXUEXIAOBANHOUCHANSHENGDEPMVsZUOYONGYURENWEIXUEGUANNEIPIXIBAO(human microvascular endothelial cells,HMECs),JIANCEHEFENXITXB2/6-keto-PGF1α(SHIJIFANYINGTXA2/PGI2DEBIZHI)HENO/ET-1BIZHIDEBIANHUA、NEIPIXINGYIYANGHUADANHEMEI(endothelial nitric oxide synthase, eNOS)DELINSUANHUASHUIPING,YILEJIEWEIXUEGUANNEIPIXIBAOGONGNENGGAIBIAN;TONGGUOJIANCEHMECsPEIYANGSHANGQINGZHONGXIBAOJIANNIANFUFENZI-1(intercellular adhesion molecule-1, ICAM-1)、XUEGUANXIBAONIANFUFENZI-1(vascular cell adhesion molecule-1, VCAM-1)HEE-XUANZESU(E-selectin)DESHUIPING,YIJINEIPIWEINANGPAO(endothelial microvesicles,EMVs)DEHANLIANG,JINYIBUPINGJIAPMVsDUIHMECsSHIFOUJUYOUSUNSHANGZUOYONG。

                            1 、CAILIAOYUFANGFA

                            1.1 、SHIJICAILIAO

                            TONGGUOJINGMAICAIJIJIANKANGZHIYUANZHEDEQUANXUE,YI1∶10TIJIDENINGMENGSUANNARONGYEKANGNING。XUESHUANSUA2(TXA2)HEQIANLIEXIANSUI2(PGI2)DEWENDINGDAIXIECHANWUTXB2HE6-keto-PGF1αDEELISAJIANCESHIJIHEGOUZICayman ChemicalGONGSI(USA); LINSUANHUAeNOSDEKANGTIGOUZIAbcamGONGSI(USA);NEIPISU-1(ET-1)KANGTIGOUZISanta CruzGONGSI(USA);ICAM-1、VCAM-1DEELISASHIJIHEGOUZISHANGHAIXINYUGONGSI;DAF-FMDA(NOYINGGUANGTANZHEN)、E-selectin ELISAGOUZISUOLAIBAOSHENGWUGONGSI;HMECsGOUZIATCC(USA)。

                            1.2 、XIBAOPEIYANG

                            HMECsCAIYONGDMEMGAOTANGPEIYANGJI(HAN10%TAINIUXUEQINGHE1%QING/LIANMEISU),ZAI37 ℃,5% CO2DEFUYUXIANGZHONGPEIYANG。CAIYONGDI3~10DAIDEHMECsYONGYUSHIYAN。

                          牛牛游戏厅安卓,{原始关键词}   1.3 、RENXUEXIAOBANFENLIJIPMVsDEZHIBEI

                          牛牛游戏厅安卓,{原始关键词}   QUNINGMENGSUANNAKANGNINGDEJIANKANGRENQUANXUE,110×gLIXIN15 minHUODEFUHANXUEXIAOBANXUEJIANG(platelet-rich plasma, PRP),QUPRPYI710×gLIXIN15 minHUODEXUEXIAOBANCHENDIAN,YICGSHUANCHONGYEXIDIXUEXIAOBAN3CI,TAISHIYEZHONGXUANXUEXIAOBANZHI3×108/mL;XUEXIAOBANXUANYEZHONGJIARUZHONGNONGDU20 μmol/L DEADP,37 ℃FUYU10 minYIJIHUOXUEXIAOBAN。710×gLIXIN15 minQUCHUHUOHUADEXUEXIAOBAN(CHENDIANBUFEN),SHANGQINGBUFENYU4 ℃YI20 000×gLIXIN60 min,DEDAODECHENDIANJIWEIPMVs,TONGSHIBAOLIUCISHANGQINGZUOWEIDUIZHAO(SupZU),YITAISHIYEZUOWEIKONGBAIDUIZHAO(control, ConZU)。CAIYONGBCASHIJIHECEDINGPMVsDEDANBAINONGDU[7]。

                            1.4 、ELISA JIANCE

                            50 μg/mL PMVsYUHMECsFUYU6、12、24 h,HUOCAIYONGBUTONGNONGDU(10、20、50 μg/mL)DEPMVsYUHMECs FUYU24 h,SHOUJIXIBAOPEIYANGSHANGQING,ANZHAOELISASHIJIHESHUOMINGSHUJIANCETXB2、6-Keto-PGF1α、ICAM-1、VCAM-1HEE-selectinDESHUIPING。

                            1.5、 NOHANLIANGCEDING

                            HMECsYI2×104GE/KONGJIEZHONGZHI96KONGBANZHONG。CAIYONGBUTONGNONGDU(10、20、50 μg/mL)DEPMVsYUHMECs FUYU24 hHOU,QIQUXIBAOPEIYANGJI,JIARUNOYINGGUANGTANZHEN(3 μmol/L DAF-FM-Da)JIXUFUYU30 min,YINGGUANGXIANWEIJING(JIFABOZHANGWEI515 nm)XIAGUANCHABINGPAIZHAO。MEIGESHIYEZHONGTONGJI25GEXIBAODEYINGGUANGQIANGDUBINGCAIYONGImage JRUANJIANJINXINGDINGLIANGFENXI。

                            1.6 、Western blotJIANCE

                            CAIYONGBUTONGNONGDU(10、20、50 μg/mL)DEPMVsFUYUHMECs 24 h。RIPALIEJIEYE(HANDANBAIMEIHELINSUANMEIYIZHIJI)LIEJIEXIBAO,SHOUJIXIBAOSHANGQINGHOUCAIYONGBCAFAJIANCEDANBAINONGDU。GEZUQUDENGLIANGDANBAIJINXINGNINGJIAODIANYONG,ZHUANMO(PVDFMO),BINGYONG5%DENIUNAISHIWENFENGBI。PVDFMOJIARUKANGET-1、LINSUANHUAeNOS(p-eNOS)HEGAPDHDEYIKANG,ZHIYUYAOCHUANGSHANG4 ℃FUYUGUOYEHOU,JIAERKANGYUSHIWENXIAFUYU1 hHOUXIDI。CAIYONGHUAXUEFAGUANGYIPUGUANGTIAODAI,SAOMIAOHOUFENXIXIANGGUANSHUJU。

                          牛牛游戏厅安卓,{原始关键词}   1.7、 LIUSHIXIBAOYIJIANCEEMVsHANLIANG

                          牛牛游戏厅安卓,{原始关键词}   CAIYONGBUTONGNONGDUDEPMVs(10、20、50 μg/mL)FUYUHMECs 24 hHOUSHOUJIXIBAOPEIYANGSHANGQING。QU100 μL HMECsPEIYANGSHANGQING,FENBIEJIARUCD31-PEKANGTIHEAnnexin V-FITCKANGTIGE5 μL,SHIWENBIGUANGFUYU20 min。YI0.2 ~1 μmDEWEIZHUZUOWEICANKAO,CAIYONGLIUSHIXIBAOYI(Verse,BDGONGSI)JIANCEHMECsPEIYANGSHANGQINGZHONGEMVs(CD31+/Annexin V+)DEHANLIANG。

                          牛牛游戏厅安卓,{原始关键词}   1.8 、TONGJIXUEFENXI

                            SHIYANJUNZHONGFU3CI,SHUJUYIx ? ±sx?±sBIAOSHI,CAIYONGGraphPad Prism 6RUANJIANJINXINGTONGJIFENXI,LIANGZUJIANBIJIAOCAIYONGtJIANYAN,DUOYANGBENCAIYONGDANYINSUFANGCHAFENXI,JIANYANSHUIZHUN:α= 0.05。

                            2 、JIEGUO

                          牛牛游戏厅安卓,{原始关键词}   2.1 、PMVsKESHINEIPIXIBAOTXB2/6-keto-PGF1αBIZHISHENGGAO

                            ELISAJIANCETXA2HEPGI2DEWENDINGDAIXIECHANWUTXB2HE6-keto-PGF1α。 JIEGUOXIANSHI,PMVsKESHIHMECsFENMIDETXB2DESHUIPINGZENGJIA,BINGCHENGJILIANGHESHIJIANYILAIXING(TU1A、B),ER6-keto-PGF1αDESHUIPINGZEMINGXIANJIANGDI(TU1C、D),DAOZHITXB2/6-keto-PGF1αDEBIZHIXIANZHESHENGGAO(TU1E、F);QIZHONG50 μg/mL PMVsZUTXB2/6-keto-PGF1αDEBIZHIJIAODUIZHAOZUSHENGGAOYUE12BEI(P<0.05),BIAOMINGPMVsKEDAOZHITXA2/PGI2BILIDEMINGXIANSHANGSHENG。

                          牛牛游戏厅安卓,{原始关键词}   2.2 、PMVsKEJIANGDIHMECsZHONGNOHANLIANGHEeNOSDELINSUANHUASHUIPING,CUJINET-1BIAODA

                          牛牛游戏厅安卓,{原始关键词}   YINGGUANGTANZHENJIANCEJIEGUOXIANSHI,50 μg/mL PMVsKEXIANZHEJIANGDIHMECsZHONGNODEHANLIANG(TU2)。eNOSSHIYOUDAONEIPIXIBAONOHECHENGDEXIANSUMEI。eNOSDANBAISer1177WEIDIANDELINSUANHUASHUIPINGJIANGDIKEDAOZHIeNOSMEIHUOXINGJIANGDI、NOSHENGCHENGJIANSHAO。TONGSHI,Western blotJIANCEJIEGUOXIANSHI,PMVsKEXIANZHEYIZHIeNOSDANBAIDELINSUANHUASHUIPING(TU3)。ZHEISHUOMINGPMVsNENGJIANGDIeNOSDELINSUANHUAHUOXING,JINERJIANSHAONODESHIFANGLIANG。

                            ET-1SHIYOUXUEGUANNEIPIXIBAOFENMIDEYIZHONGQIANGLIEDEXUEGUANSHOUSUODIAOJIEYINZI,ZAIWEICHIJICHUXUEGUANZHANGLIHENEIPIGONGNENGWENTAIZHONGJUYOUZHONGYAOZUOYONG。Western blotJIANCEJIEGUOXIANSHI,YUDUIZHAOZUBIJIAO,PMVsNENGGOUXIANZHEZENGJIAHMECsZHONGET-1DANBAIDEBIAODA(TU3)。

                            2.3 、PMVs可促进HMECs培养上清中ICAM-1、VCAM-1和E-selectin表达

                            10、20、50 μg/mL PMVsCIJIHMECs 24 hHOU,ELISAJIANCEXIBAOPEIYANGSHANGQINGZHONGDEICAM-1、VCAM-1HEE-selectin(TU4)。JIEGUOXIANSHI,YUDUIZHAOZUBIJIAO,50 μg/mL PMVsKECUJINHMECsFENMIICAM-1、E-selectin,CHAYIJUYOUTONGJIXUEYIYI(P<0.05)。10、20、50 μg/mL PMVsJUNKECUJINHMECsFENMIVCAM-1,CHAYIJUYOUTONGJIXUEYIYI(P<0.05)。

                            2.4、 PMVs可促进HMECs产生EMVs

                          牛牛游戏厅安卓,{原始关键词}   LIUSHIXIBAOSHUDINGLIANGJIANCEJIEGUOXIANSHI,20、50 μg/mL PMVsCIJIHMECs 24 hHOU,EMVsDESHIFANGJIAOConZUHESupZUMINGXIANZENGJIA(P<0.05,TU5、6)。

                            图1 PMVs对HMECs培养上清中TXB2和6-keto-PGF1α水平的影响(n=3,±s)
                          图1 PMVs对HMECs培养上清中TXB2和6-keto-PGF1α水平的影响(n=3,±s)

                            A、C、E:GEZUZUOYONGYUHMECsXIBAO24 h a:P<0.05,YUConZUBIJIAO;b:P<0.05,YUSupZUBIJIAO;c:P<0.05,YU10μg/mL PMVsZUBIJIAO;d:P<0.05,YU20μg/mL PMVsZUBIJIAO;B、D、F:50μg/mL PMVsZUOYONGYUHMECsBUTONGSHIJIANa:P<0.05,YU0 hBIJIAO;b:P<0.05,YU6 hBIJIAO;c:P<0.05,YU12 hBIJIAO

                          牛牛游戏厅安卓,{原始关键词}   TU2 PMVsDUIHMECsZHONGNOSHUIPINGDEYINGXIANG(n=3,±s)

                          牛牛游戏厅安卓,{原始关键词}   A~E:YINGGUANGXIANWEIJINGXIAGUANCHAGEZUHMECsZHONGNOHANLIANGDEBIANHUA;F:GEZUZUOYONG24 hHOUHMECsZHONGNOHANLIANGDEBIANHUAa:P<0.05,YUConZUBIJIAO;b:P<0.05,YUSupZUBIJIAO

                            图3 Western blot检测PMVs对HMECs中ET-1和p-eNOS表达的影响(n=3,±s)
                          图3 Western blot检测PMVs对HMECs中ET-1和p-eNOS表达的影响(n=3,±s)

                          牛牛游戏厅安卓,{原始关键词}   A:Western blotJIANCEp-eNOSHEET-1DEDANBAIHANLIANG;B-C:BANDINGLIANGFENXIJIEGUO;a:P<0.05,YUConZUBIJIAO;b:P<0.05,YUSupZUBIJIAO

                            图4 PMVs对HMECs培养上清中ICAM-1、VCAM-1和E-selectin水平的影响(n=3,±s)
                          图4 PMVs对HMECs培养上清中ICAM-1、VCAM-1和E-selectin水平的影响(n=3,±s)

                          牛牛游戏厅安卓,{原始关键词}   A-C:PMVsFUYU24 hHOUJIANCEXIBAOPEIYANGSHANGQINGZHONGICAM-1、VCAM-1HEE-selectinDEFENMIa:P<0.05,YUDUIZHAOZU(Con)BIJIAO;b:P<0.05,YUPMVsSHANGQING(Sup)ZUBIJIAO

                            图5 流式细胞术检测各组HMECs培养上清中的EMVs(CD3+/Annexin V+)(n=3,±s)
                          图5 流式细胞术检测各组HMECs培养上清中的EMVs(CD3+/Annexin V+)(n=3,±s)

                            图6 PMVs对各组HMECs培养上清中EMVs含量的影响(n=3,±s)
                          图6 PMVs对各组HMECs培养上清中EMVs含量的影响(n=3,±s)

                            A:GEZULIUSHIXIBAOSHUJIANCEJIEGUOa:P<0.05,YUConZUBIJIAO;b:P<0.05,YUSupZUBIJIAO;B:EMVsDEFSC-ASANDIANTU

                            3 、讨论

                            WEIXUEGUANNEIPIXIBAOSHIXUEYEHEWEIXUEGUANBIZHIJIANDEYICENGGAODUXUANZEXINGPINGZHANG,TONGGUODIAOJIEWEIXUEGUANDETONGTOUXINGHEWANZHENGXING,CANYUXUEYEHEZUZHIJIANDEWUZHINENGLIANGDAIXIE。CIWAI,WEIXUEGUANNEIPIXIBAOYESHIYIZHONGJUYOUFENMIGONGNENGDEXIBAO,KETONGGUOHECHENGHESHIFANGDUOZHONGXIBAOYINZIHEXUEGUANHUOXINGWUZHI,RUTXA2、PGI2、NO、ET-1、ICAM-1、VCAM-1JIE-selectinDENGDIAOJIEXUEGUANSHOUSUOHESHUZHANG,CONGERWEICHIXUEGUANWENTAIHEXUEGUANGONGNENG。WEIXUEGUANNEIPIGONGNENGZHANGAISHIWEIXUEGUANNEIPIXIBAOZAIDUOZHONGBINGLIYINSUCIJIXIACHUXIANDEGONGNENGYICHANG,BIAOXIANWEIWEIXUEGUANZHANGLIDIAOJIEZHANGAIHENIANFUFENZIBIAODAYICHANG,SHIZHONGDUOJIBINGFASHENGDESHIDONGHUANJIE。LIRU,ZAIXINXUEGUANJIBINGGAOWEIYINSURUGAOXUEYA、TANGNIAOBING、YANZHENG、XIYAN、XUEZHIYICHANGDENGDECANYUXIA,GUANMAINEIPIXIBAOSHOUSUN,DAOZHILECMDDEFASHENG[8]。CIWAI,XINJIQUEXUEZAIGUANZHUSUODAOZHIDEWEIXUEGUANNEIPISUNSHANGBEIRENWEISHIPCISHUHOU“WUFULIU”XIANXIANGFASHENGDEZHONGYAOYUANYINZHIYI[9]。XUEXIAOBANSHIXUEGUANBIYANZHENGFANYINGDEZHONGYAOCANYUCHENGFEN。XUEXIAOBANMUJIDAOXUEGUANSUNSHANGBUWEIHOU,XUNSUBEIJIHUO,NIANFU、JUJIYUWEIXUEGUANNEIPI,DAOZHIWEIXUESHUANXINGCHENGHEWEIXUEGUANZUSAI[10]。HUOHUADEXUEXIAOBANJIQIJIHUOHOUCHANSHENGDEPMVsHAIKESHIFANGDALIANGXIBAOYINZIHEQUHUAYINZI,ZHAOMUBAIXIBAONIANFUZHISHOUSUNXUEGUANBIJUBU,JIAJUJUBUYANZHENGFANYING,DAOZHINEIPIXIBAOTONGTOUXINGZENGJIA,WEIXUEGUANSHENLOUZENGDUO,WEIXUEGUANGONGNENGZHANGAI[11]。

                            TXA2/PGI2DEDONGTAIPINGHENGZAIDIAOKONGNEIPIXIBAOTONGTOUXING、WEICHIWEIXUEGUANGONGNENGFANGMIANJUYOUZHONGYAOZUOYONG。PGI2ZHUYAOYOUXUEGUANNEIPIXIBAOCHANSHENG,PGI2KETONGGUOJIHUOXIANGANSUANHUANHUAMEI,SHANGDIAOXUEXIAOBANcAMPSHUIPING,JIEKANGTXA2DECUXUEGUANSHOUSUOHEXUEXIAOBANJUJIZUOYONG。BINGLIQINGKUANGXIA,ERZHEJIANPINGHENGBEIDAPO,DAOZHINEIPISUNSHANGHEGONGNENGZHANGAI。TXA2HEPGI2DEBANSHUAIQIJIAODUANQIEBUWENDING,YINCIZAIYANJIUZHONGZHUYAOTONGGUOJIANCETXA2HEPGI2DEWENDINGDAIXIECHANWUTXB2HE6-keto-PGF1αYIFANYINGQISHUIPING[12]。BENYANJIUFAXIAN,PMVsKEMINGXIANZENGJIAHMECsPEIYANGSHANGQINGZHONGTXB2SHUIPING,TONGSHIJIANGDI6-keto-PGF1αSHUIPING,DAOZHIHMECsPEIYANGSHANGQINGZHONGTXB2/6-keto-PGF1αDEBIZHIXIANZHESHENGGAO。BIAOMINGPMVsNENGGANRAONEIPIXIBAOTXA2/PGI2DEPINGHENGZHUANGTAI,DAOZHINEIPIYILAIXINGXUEGUANSHUSUOGONGNENGSHOUSUN。

                            NOHEET-1SHIYOUXUEGUANNEIPIXIBAOHECHENGHEFENMIDEYIDUIXUEGUANSHUSUOYINZI,LIANGZHEBAOCHIYIDINGDEPINGHENGSHIWEICHIZHENGCHANGXUEGUANGONGNENGZHUANGTAIDEZHONGYAOYINSU。NOSHIL-JINGANSUANZAIeNOSDECUIHUAZUOYONGXIAHECHENGDEYIZHONGCUXUEGUANSHUZHANGWUZHI。CIWAI,NOHAIJUYOUYIZHIBAIXIBAOYUNEIPIXIBAONIANFU、YIZHIXUEXIAOBANNIANFUHEJUJIDENGZUOYONG。ERET-1SHIYIZHONGNEIPIYUANXINGDEQIANGXIAOXUEGUANSHOUSUOTAI,ZAIDIAOJIEXUEGUANZHANGLIZHONGFAHUIZHEZHONGYAODEZUOYONG。BENYANJIUFAXIAN,PMVsKETONGGUOXIADIAOHMECsZHONGeNOSDANBAILINSUANHUASHUIPING(Ser1177WEIDIAN)ERJIANGDIeNOSDEHUOXING,DAOZHINODESHENGCHENGHESHIFANGQUEXIAN,TONGSHICUJINET-1DANBAIDEBIAODA,CONGERPOHUAINO/ET-1PINGHENG,SHIDEXUEGUANNEIPIXIBAOBIAOXIANWEISHOUSUOGONGNENGYOUSHIERSHUZHANGGONGNENGZHANGAIDEZHUANGTAI,DAOZHINEIPIXIBAOGONGNENGWENLUANDEFASHENG。ZHENGCHANGQINGKUANGXIA,XUEGUANNEIPIXIBAOZHONGICAM-1、VCAM-1JIE-selectinDEBIAODALIANGHENDI,DANGNEIPIXIBAOYANZHENGHUOSUNSHANGSHI,NENGZAIDUOZHONGXIBAOYINZIDECHUFAXIAXUNSUSHENGGAO。BENYANJIUFAXIANXUEXIAOBANHUOHUAHOUCHANSHENGDEPMVsNENGSHANGDIAONEIPIXIBAOZHONGICAM-1、VCAM-1JIE-selectinDEBIAODASHUIPING,BIAOMINGXUEXIAOBANKETONGGUOSHIFANGPMVsCANYUBAIXIBAOHEXUEGUANNEIPIXIBAOZHIJIANDENIANFUJILIANFANYINGCONGERJIAZHONGYANZHENGFANYING。

                            XIBAOWAINANGPAO(extracellular vesicles,EVs)SHIXIBAOFENMIDEYILEICHAOWEIMOXINGNANGPAO,BAOKUOWAIMITI(exosomes)、WEINANGPAO(microvesicles, MVs)HEDIAOWANGXIAOTI(apoptotic bodies)[13,14]。WAIMITISHIYOUDUONANGPAOTIYUXIBAOMORONGHEXINGCHENGDEZHIJINGWEI30~150 nmDEEVs,WEINANGPAOZESHIYOUXIBAOMOCHUYAXINGCHENGDEZHIJINGWEI100~1000 nmDEEVs[15]。EMVsSHINEIPIXIBAOJIHUOHUODIAOWANGSHISHIFANGDEWEINANGPAO。LINCHUANGYANJIUFAXIAN,TANGNIAOBING、XUEGUANGAIHUADENGXINXUEGUANJIBINGFASHENGSHI,BINGRENXUEJIANGZHONGEMVsDEFENMIZENGJIA,JIAZHONGLEXUEGUANJUBUYANZHENGFANYING[16]。XUNHUANXUEZHONGEMVsZAISUOYOUWEILIZUFENZHONGSUOZHANBILIDESHENGGAOKEZUOWEINEIPIXIBAOSUNSHANGHEGONGNENGWENLUANDEBIAOZHI。BENYANJIUFAXIAN,PMVsKEXIANZHECUJINHMECsSHIFANGEMVs,TISHIPMVsDUIHMECsJUYOUSUNSHANGZUOYONG。

                            BENYANJIUFAXIAN,PMVsKESHIHMECsZHONGTXA2/PGI2DEBIZHISHENGGAO,ERNO/ET-1DEBIZHIXIAJIANG,CONGERDAOZHINEIPIXIBAOGONGNENGZHANGAI;TONGSHISHANGDIAOHMECsZHONGICAM-1、VCAM-1、E-selectinDESHUIPING,YIJICUJINEMVsDEFENMI,TISHIPMVsKENENGTONGGUOSHANGSHUYINGXIANGDAOZHINEIPIXIBAOSUNSHANGHENEIPITONGTOUXINGZENGJIA。BENYANJIUJINYIBUCHANMINGLEXUEXIAOBANYUWEIXUEGUANGONGNENGZHANGAIZHIJIANDEGUANXI,KEWANGWEIWEIXUEGUANGONGNENGZHANGAIHEGUANZHUANGDONGMAIWEIXUEGUANJIBINGDEFANGZHITIGONGXINDESILU。

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