目的探讨暴露于大气细颗粒物后,C57BL/6和C3H/He两种品系小鼠在肺损伤过程中信号通路是否存在差异。方法采用气管滴注的染毒方法,两种品系的小鼠(C57BL/6小鼠和C3H/He小鼠)均予大气细颗粒物染毒,连续染毒2天,最后一次染毒24小时后,处死小鼠,取肺组织,并且立即置于液氮中保存。然后运用AffymetrixMouse4302.0表达谱基因芯片,分析挖掘在两种品系小鼠肺部有差异的信号通路。结果在染毒前,基因Igh-6、Mmp2、Timp1、Col1a1、Col1a2、C4和Hc的表达在C57BL/6和C3H/He小鼠之间的比值分别为:0.00、-2.40、0.00、-4.42、-4.92、6.65和-1.93,但是在染毒后,比值变为:-2.83、2.15、-2.18、2.40、2.86、4.23和2.18。通过数据挖掘,找到3条有差异的信号通路,包括:炎症反应通路、基质金属蛋白酶通路和经典的补体激活通路。结论3条有差异的信号通路都直接和炎症反应相关,而且最终都表现为在C57BL/6品系小鼠肺部的炎症反应比C3H/He品系小鼠更加剧烈,提示由于遗传背景的不同导致了这种差异的产生。
Objective To study the differences of signaling pathway of lung injury between C57BL/6 and C3H/He mice exposed to fine particle. Methods By intratracheally instillation, two strains of mice (C57BL/6 mice and C3H/He) were exposed to fine particle once time per day, for continuously two days. Twenty-four hours after last time exposure, the mice were killed and the lungs were taken out immediately, and put into the liquid nitrogen. By using Affymetrix430 2.0 geneehip, differences of the signaling pathways between C57BL/6 and C3H/He mice were found. Results It was indicated that the ratios of (C57BL/6)/ (C3H/He) of lgh-6, Mmp2, Timpl, Collal, Colla2, C4 and Hc expression in unexposed mice,and in exposed mice were 0.00, -2.40, 0.00, -4.42, -4.92, 6.65 and - 1.93, and -2.83, 2.15, - 2.18, 2.40, 2.86, 4.23 and 2.18, respectively. And by further analysis, three different signaling pathways were discovered between C57BL/6 and C3H/He mice, including inflammatory response pathway, matrix metalloproteinases pathway and classical complement activation. Conclusion The results showed that three signaling pathways were associated with inflammation. It was suggest that the lung inflammation in C57BL/6 mice could be more severe than that in C3H/He mice. The possible causation may be the different genetic background between C57BL/6 and C3H/He mice.