摘要
目的从血管内皮活性物质角度探讨免疫性血小板减少症(immunethrombocytopenia,ITP)气不摄血证血管损伤情况及出血机制的动态变化。方法采用睡眠剥夺复合免疫法制备ITP气不摄血证小鼠模型,第1周进行睡眠剥夺,第2、3周睡眠剥夺同时注射抗血小板血清(APS)进行免疫。将Balb/C小鼠分为正常组和模型组,各组再分为7、10、21 d时间点,每个时间点正常组10只、模型组12只,观察各时间点小鼠体征,检测小鼠体质量及血小板、抓力、脾脏指数、胸腺指数,ELISA检测血清血管性血友病因子(vWF)、一氧化氮(NO)、内皮素-1(ET-1)含量,Aim Plex流式高通量多因子法检测血管内皮生长因子-A(VEGF-A)、可溶性细胞间黏附分子-1(sICAM-1)、可溶性血管细胞黏附分子-1(sVCAM-1)含量。结果与正常组比较,模型组第7日小鼠精神状态萎靡,倦怠蜷缩,极少活动,此状态随时间延长日益加重,体质量、抓力、血小板、脾脏指数、胸腺指数显著降低(P<0.01),v WF、NO、ET-1显著升高(P<0.01);注射APS后,模型组小鼠腹部、腿部有出血点,便血情况发生,第2次注射后出血最为严重,此后逐日减轻,小鼠体质量、抓力、血小板、胸腺指数、VEGF-A、sVCAM-1显著降低(P<0.01,P<0.05),脾脏指数、vWF、NO、ET-1显著升高(P<0.01);第21日模型组小鼠出血较轻,体质量、抓力、血小板、胸腺指数显著降低(P<0.01),脾脏指数、vWF、NO、ET-1、sICAM-1显著升高(P<0.01)。结论 ITP气不摄血证小鼠模型存在血管损伤:造模第7日以血管内皮凝血功能紊乱为主,第10日以血管内皮通透性改变为主,第21日以血管内皮免疫功能紊乱为主。
Objective To explore the dynamic changes of vascular injury and bleeding mechanism of immune thrombocytopenia(ITP) with syndrome of qi failing to control blood from the perspective of vascular endothelial active substances. Methods ITP with syndrome of qi failing to control blood model was built by sleep deprivation combined with immunoassay. Mice were subjected to sleep deprivation at week 1 and sleep deprivation with immunization with anti-platelet serum(APS) at week 2 and 3. Mice were divided into normal group and model group, and divided into three time points: 3 d, 10 d, 21 d. There were 10 mice in the normal group and 12 mice in the model group at each time point. Body signs of each time point were observed and body weight, platelet, grip, spleen index, and thymus index were recorded. vWF, NO and ET-1 were measured by ELISA. VEGF-A, sICAM-1, sVCAM-1 were measured by Aim Plex flow high-throughput multifactor. Results Compared with the normal group, after 7 days of sleep deprivation, mice in the model group were mentally depressed, tired and curled up with little activity. This state increased with the deprivation time. The body weight, grip, platelet, spleen index and thymus index of the mice significantly decreased(P<0.01), and vWF, NO and ET-1 significantly increased(P<0.01). After the injection of APS, the bleeding point appeared in the abdomen and legs of the mice and hematochezia occurred in mice. After the second injection, the bleeding was the most serious, and then decreased day by day, the mouse weight, the grip, the platelets, thymus index, VEGF-A and sVCAM-1 significantly decreased(P<0.01, P<0.05), and the spleen index, vWF, NO and ET-1 significantly increased(P<0.01). There was less bleeding on the 21 st day. The body weight, grip, platelet and thymus index of the mice significantly decreased(P<0.01), and the spleen index, v WF, NO, ET-1 and s ICAM-1 significantly increased(P<0.01). Conclusion Vascular injury is found in the model of ITP with syndrome of qi failing to control blood. On the 7 th day, vascular endothelial coagulation dysfunction is dominant, on the 10 th day, change of vascular endothelial permeability is dominant, and on the 21 st day, vascular endothelial immune dysfunction is dominant.
作者
武曲星
王攀
王冬芝
蔺亚东
张伏芝
刘建勋
任钧国
WU Quxing;WANG Pan;WANG Dongzhi;LIN Yadong;ZHANG Fuzhi;LIU Jianxun;REN Junguo(Graduated School,Beijing University of Chinese Medicine,Beijing 100029,China;Beijing Key Laboratory of Pharmacology of Chinese Materia Medica,Institute of Basic Medical Sciences of Xiyuan Hospital,China Academy of Chinese Medical Sciences,Beijing 100091,China)
出处
《中国中医药信息杂志》
CAS
CSCD
2019年第12期56-61,共6页
Chinese Journal of Information on Traditional Chinese Medicine
基金
国家重点基础研究发展计划(2015CB554405)
国家科技重大专项-重大新药创制(2017ZX09301018)
关键词
免疫性血小板减少症
气不摄血证
血管活性物质
病证结合模型
immune thrombocytopenia
syndrome of qi failing to control blood
vasoactive substances
syndrome combination model
