摘要目的 通过大鼠静脉血栓栓塞症(VTE)模型,观察股静脉血栓形成(DVT)和肺血栓栓塞症(m)时血栓和血管内膜的变化.方法 健康清洁级SD大鼠78只,3～6个月龄,雌雄各半,随机分为DVT组(18只)、DVT-PTE组(54只)及对照组(6只).DVT和DVT-PTE组大鼠均采用显微血管夹阻滞左侧股静脉血流的方法制备DVT模型.DVT组在DVT建模后第1、4、7天分别处死大鼠6只,共3组(D1、D4、D7),行左股静脉病理学检查;DVT-PTE组大鼠在DVT建模后第1、4、7天分别取出左股静脉血栓,注入右股静脉,制备DVT-PTE模型,PTE建模后第1、4、7天分别处死3组大鼠,共9组[D1P1、D4P1、D1P7、D4P1、D4P4、D4P7、D7P1、D7P4及D7P7],行肺组织病理学检查.统计学方法采用卡方检验和方差分析.结果 (1)DVT建模后第1天,模型成功率100%(24/24);大体观股静脉血栓阳性率在第7天[42%(10/24)]明显低于第1天(X2=19.765,P<0.01).DVT模型成功率在D1、D4、D7组分别为100%(18/18)、83%(15/18)、44%(8/18),其中D7组明显低于D1(X2=13.846,P<0.01)和D4(X2=5.900,P<0.05)组.(2)光镜检查:DVT后第1、4、7天,股静脉内分别见红色、混合和机化血栓.以DVT建模后第4、7天的栓子栓塞肺动脉,栓子溶解性降低,D4Pn和D7Pn组[73%(11/15)和100%(8/8)]大体观肺脏血栓阳性率明显高于D1Pn组[39%(7/18)](X2=3.915,P<0.05;X2=8.474,P<0.01).D1P7、D4P4、D7P4和D7P7组非栓塞肺动脉管壁面积与血管总面积比值增加,与对照组比较,均P<0.05.(3)电镜检查血管肇改变:①D1组股静脉内皮细胞间连接断裂,内弹力板裸露;D4组股静脉内皮细胞肿胀、核增大,部分内皮细胞和内弹力板消失;D7组股静脉血管壁结构消失.②以DVT建模后第1、4天的栓子栓塞肺动脉,肺动脉血管内皮细胞第1天发生肿胀、增生、核增大;第4和7天内皮细胞增生,内弹力板增厚,成纤维细胞增生.而以DVT建模后第7天的栓子栓塞肺动脉,在第1天即出现内皮细胞线粒体肿胀和内弹力板消失较为明显,第4和7天中膜增厚,成纤维细胞增生.结论 大鼠DVT-PTE模型肺动脉血栓的阳性率和转归受DVT不同时间栓子的影响;VTE时受累股静脉和肺动脉可出现血管内皮细胞和内弹力板的改变.

abstractsObjective To observe the changes of thrombi and vessel intima in a rat model of venous thromboembolism (VTE). Methods Seventy-eight SD rats were randomly divided into deep vein thrombosis (DVT) group (n=18), deep vein thrombosis-pulmonary thromboembolism (DVT-PTE) group (n=54) and control group (n=6). Rats in DVT and DVT-PTE groups were undergoing local blocking of left femoral artery with micro vessel clip to cause DVT. One, 4, and 7 days later 6 rats from DVT group were killed with their femoral veins observed by light and electron microscopy. Rats in DVT-PTE group underwent injection of the thrombi from left femoral vein solution in normal saline into the right femoral vein 1,4, and 7 days after DVT formation to establish model of DVT-PTE. The 6 rats of each subgroup [Dn(1,4,7)>Pn(1,4,7) subgroups]were killed 1,4, and 7 days after DVT-PTE formation respectively with their lungs observed by light and electron microscopy. Results (1)On day 1 after DVT, the successful rate of DVT was 100%. The positive hrombus rate in femoral veins on gross is lower on day 7 after DVT[42% (10/24)] than that on day 1 after DVT (X2=19.765, P<0.01). The successful rates of DVT-PTE model were 100% (18/18), 83% (15/ 18)、44% (8/18)in the D1Pn, D4Pn and D7Pn subgroups respectively. The successful rate of DVT-PTE model is lower in the D7Pn subgroups than that in the D1Pn (X2=13.846, P<0.01) and D4Pn(X2=5.900, P<0.05) subgroups. (2)One, 4, and 7 days after DVT, there were reddish, mixed, and organized thrombi in femoral veins. The thrombi in pulmonary arteries caused by the 4 or 7 days thrombi of DVT howed lower dissolubility than that from one day thrombi of DVT. The positive thrombus rate in pulmonary arteries on gross is higher in the D4Pn and D7Pn subgroups [73%(11/15)and 100% (8/8)] than that in the D1Pn subgroups[39% (7/18, X2=3.915, P<0.05;X2=8.474, P<0.01)]. The ratio of vessel wall area and total vessel increased in D1P7、D4P4、D7P4 and D7P7 subgroups compared to the control group (P= 0.03,0.00,0.00,0.011, respectively). (3)The junctures of femoral venous endothelial cells were ruptured and the intra-elastic layers were exposed on the 1st day, then the endothelial cells and intra-elastic layers became to disappear on the 7th day. The hyperplasia of pulmonary arterial intimal were observed on the 4th or the 7th day after the thrombi in pulmonary arteries caused by the 1 or 4 days thrombi of DVT. However, pulmonary arterial endothelial cells and intra-elastic layers maybe disappear on the 1st day after the thrombi in pulmonary arteries caused by the 7 days thrombi of DVT. Conclusions The age and nature of thrombi before the embolization are related to the outcome of emboli and pulmonary arterial intimal alterations. For intimal, there are the changes of hyperplasia, intra-elastic layers thickening and even disappearance in femoral veins and pulmonary arteries after VTE.