基质金属蛋白酶及其抑制剂在RSV感染诱发哮喘中的作用

The balance of MMP-9 and TIMP-1 maybe the important pathological mechanism of asthma induced by RSV infection

目的本研究通过观察RSV感染致敏小鼠MMP-9和TIMP-1的表达与肺组织病理的变化,探讨RSV感染诱发哮喘发作的发病机制。方法分3组,分别是安慰剂(生理盐水)对照组、RSV感染小鼠模型组、OVA致敏小鼠模型组,分别作免疫组织化学染色(SP法)和HE,染色观察肺组织病理变化观测MMP-9 mRNA、TIMP-1mRNA的表达。结果本实验观察到RSV感染小鼠模型组呼吸道组织MMP-9高表达,TIMP-1亦随之有所升高,以MMP-9的表达升高为主,两者比值较安慰剂对照组升高。病理上表现为炎症细胞的浸润为主。而OVA致敏组则表现为TIMP-1过度表达,两者比值较安慰剂对照组降低,病理上出现气道基质增生,纤毛上皮剥落,气道壁纤维化。免疫组化结果显示RSV感染致敏组MMP-9为13312.3±4462.5,TIMP-1为4481.8±2320.3,OVA致敏组MMP-9为4590.8±2320.3,TIMP-1为7477.5±2205.8,两者差异有统计学意义(P<0.01)。结论 MMP-9和TIMP-1两者的平衡是气道黏膜生理中的关键因素,当RSV感染导致气道炎症时,MMP-9和TIMP-1两者的平衡被打破,MMP-9高表达,而此后机体对MMP-9和TIMP-1平衡的调节导致TIMP-1随之持续升高最终使气道黏膜高反应性甚至气道黏膜重塑,这可能就是RSV感染诱导哮喘发生发展的重要疾病机制。

Objective To explore the pathogenesis of asthmatic attack by surveying the expression of MMP-9 and TIMP- 1, and the pathological changes of lung tissue in mice infected by RSV. Methods The mice were divided into three groups ： the placebo group （saline control group）, OVA infection group, and RSV infection group. We surveyed the pathological changes of lung tissue by immunohistochemical methods and HE stain. Results Compared with the placebo group, the pathology showed the airways spasm, and a large number of inflammatory cells infiltration, mainly eosinophilic grannlocyte and lymphocyte in the mice of RSV infection group ; but the pathology showed the airway epithelial hyperplasia of finger, luminal contents increased, un- der the epithelium fibrosis, mainly monocytes and lymphocytes in the mice of OVA infection group. The results indicated that the levds of MMP-9 mRNA expression in the RSV infection group were higher than those in the OVA infection group, but the levels of TIMP-1 mRNA expression in the RSV infection group were lower than those in the OVA infection group. The results of immunohistochemical method indicated that the levels of MMP-9 were 13312. 3 ± 4462. 5 and 4590. 8 ± 2320. 3, TIMP-1 were 4481.8 ± 2320. 3and 7477. 5 ±2205. 8 in RSV infection group and OVA infection group, respectively. There is statistical significance between the two groups （ P 〈 0. 01 ）. Conclusion The balance of MMP-9 and TIMP-1 is the key factor in airway mueosal physiology. When RSV infection leading to airway inflammation, the balance of MMP-9 and TIMP-1 was broken, high expression of MMP-9 and then continuing rise of TIMP-1 resulted in high reaction of airway mucosa or even the airway mucosa remodeling. This maybe the important pathological mechanism of the occurrence and development of asthma induced by RSV infection.