SARS-CoV感染后人ACE2转基因小鼠肺组织一氧化氮合酶的变化

Changes of Nitric Oxide Synthase in the Lung of SARS-CoV Infected Mice Transgenic for Human ACE 2

目的利用人血管紧张素转换酶2(ACE2)转基因小鼠模型研究一氧化氮(NO)在严重急性呼吸综合症(SARS)发病中的作用。方法用PUMC01株SARS-CoV感染野生型及人ACE2转基因小鼠,免疫印迹、免疫组化及分光光度法观察两组动物在感染后3、7d肺组织诱导型一氧化氮合酶(iNOS)和血清NO的变化。结果免疫印迹显示,在接种病毒后3d和7d的转基因小鼠肺组织iNOS蛋白密度明显增高。免疫组化显示,接种病毒后3d和7d转基因小鼠肺组织巨噬细胞增多,iNOS表达呈明显的阳性反应。生化测定血清NO结果显示,接种病毒后3d,与攻毒前及相同时间的野生型小鼠相比,NO水平明显升高。结论NO在SARS发病的病理生理过程中可能发挥重要的作用。

Objective To study the role of nitric oxide synthase （NOS） in severe acute respiratory syndrome （SARS） by using human angiotensin-converting enzyme 2 （ACE2） transgenic mice. Methods Wild-type mice and human ACE2 transgenic mice were inoculated with PUMCOI strain of SARS-CoV. The changes of inducible nitric oxide synthase in the lung tissue and serum nitric oxide from animals of two groups were detected by Western blot, immunohistochemistry and spectrophotometry at days 3 and 7 after inoculation. Results The density of iNOS protein in transgenic mice lung detected by Western blot was higher than that in wild-type mice at days 3 and 7 after inoculation. The immunohistochemical examination showed more monocytes and macrophages depicting obvious positive signals in the lungs of transgenic mice at days 3 and 7 after inoculation. Compared with the transgenic mice before inoculation and the wild-type mice at the same time point, the trangenic mice at day 3 after inoculation had higher NO level in the serum. Conclusion NO may play an important role in pathogenesis of SARS.