肺栓塞大鼠肺组织中TF、TFPI、IL-18、IL-10的表达变化及相互关系的研究

Change and relationship of tissue factor,tissue factor pathway inhibitor,interleukin-18 and interleukin-lO in rats with pulmonary thromboembolism

目的通过建立大鼠肺血栓栓塞（pulmonary thromboembolism，PTE）模型，观察不同阶段肺组织中组织因子（tissue factor，TF）、组织因子途径抑制物（tissue factor pathway inhibitor，TFPI）、IL-18、IL-10的动态变化，研究TF、TFPI、IL-18、IL-10在PTE中的作用，探讨其之间的相互关系。方法健康雄性大鼠35只，随机分为5组，每组7只：对照组、栓塞1d组、栓塞3d组、栓塞8d组、栓塞14d组；将栓子经颈静脉注入，并在第14天进行第2次栓塞，制备PTE模型；在不同时间处死大鼠，取出肺组织；HE染色观察肺组织的病理变化；采用免疫组织化学方法分别检测TF、TFPI、IL-18、IL-10在肺组织表达情况。结果实验组TF、TFPI、IL-18、IL-10第1天较对照组显著升高（P〈0．05），第3天、第8天逐渐下降，第14天较第1天升高（P〈0．05）。实验组TFPI与TF的表达呈直线正相关（r=0．84，P〈0．0001）；实验组IL-10与IL-18的表达呈直线正相关（r=0．74，PdO．0001）；实验组IL-18与TF的表达呈直线正相关（r=0．68，P〈0．0001）。结论PTE同时存在凝血活性及炎症反应增强，凝血与炎症反应密切相关；栓塞初期机体TF、TFPI、IL-18、IL-10均被激活；实验组不同时间段TF、TFPI、IL-18、IL-10的表达是变化的，并且与病情平行，可作为PTE病情评估的参考指标。

Objective To explore the change and relationship of tissue factor （TF）, tissue factor pathway inhibitor （TFPI） ,interleukin-18 （ IL-18）, and interleukin-10 （IL-10） at different stages in lung tissue of rat model with pulmonary thromboembolism （PTE）. Methods 35 male rats were randomly divided into five groups：embolism 1-day, 3-day, 8-day, 14-day and control group. The rats in embolism 14 day group were received embolus injection again at the 14th day. The rats were sacrificed at different time and lung tissues were kept for testing. The expressions of TF,TFPI,IL-18,and IL-10 in lung tissue were tested by immunohistochemistry. Results The expressions of TF, TFPI, IL-18, and IL-10 in rats of embolism 1-day group were higher than those in control group （ P 〈0.05） ,and decreased at the 3rd day and the 8th day after embolism gradually,and those at the 14th day after embolism were higher than those at the 1st day after embolism （P 〈0.05）. In the PTE group, the expression of TFPI was positively associated with TF （ r = 0.84, P 〈0. 000 1）, IL-10 was positively related to IL -18 （ r = 0.74, P〈 0. 000 1）, and IL-18 was positively linked to TF （ r = 0.68, P 〈0. 000 1）. Conclusions There are hypercoagulability activity and high inflammatory response state in PTE, and inflammation and coagulation system are closely associated with each other. They may be reference indexes for the assessment of severity of PTE.