Study On Aquaporin 4 And P65 In The Death Cases Of Enterovirus 71-induced With Neurogenic Pulmonary Edema

Objective: To investigate the expression of AQP4 and P65 in lung and brain tissues of patients with enterovirus 71(EV71)infection complicated with neurogenic pulmonary edema(NPE),and to explore the meaning of expression of both AQP4 and P65 in the pathogenesis of neurogenic pulmonary edema.Methods: 10 deaths cases from 7 hospitals of Guilin area in March 2010-June 2014 were admitted to the hand,foot and mouth disease with pulmonary edema deaths(infected with enterovirus EV71 by pathogen detection).At the same time,10 cases of interstitial pneumonia complicated with pulmonary edema and non-EV71 infection in Guilin were collected.Grouping:(PE)group:a total of 10 patients with EV71 infection complicated with pulmonary edema as the research object;10 cases of non-EV71 infection with pulmonary edema died in the same period as the control group.After the anatomical examination of the above dead cases,the gross morphology of the organs were observed and recorded.In this study,paraffin-embedded lung and brain tissue samples were prepared and made into pathological sections(4?m)for histopathologicalexamination.The pathological changes of lung and brain tissues of the death cases were observed by HE staining.The expression of AQP4 and P65 in the lung and brain tissues in both groups were qualitative detected by immunohistochemistry.Semi-quantitative detection of AQP4 and P65 was performed using integrated optical density(IOD).Results: The general appearance of tissues:(1)lung tissues: the film-like dark red congestion or bleeding on the surface of the lungs and sections,pulmonary lobular vasodilatation congestion and alveolar cavity filled with pink edema fluid in both of PE and control groups.(2)Brain tissue: PE group: the brain gland shallow,brain width widened,no more no bleeding and tumor,and brain parenchyma no obvious edema,softening and bleeding in control group.HE staining of histopathological changes:(1)lung tissue: interstitial capillary dilation,congestion,partial widening of alveolar septum,more infiltration of inflammatory cells,partial alveolar cavity filled with red blood cells and pink edema fluid in both of PE and control groups.(2)brain tissue: PE group:neuronal degeneration,necrosis,the formation of the phenomenon of neuronophagia,microglia phagocytosis of inflammatory cells to form glial nodules,inflammatory cells form cuff-like infiltration around small blood vessels.But the brain tissue of the control group did not see the phenomenon of phagocytic nerve and infiltration of inflammatory cells.Immunohistochemical results showed:(1)The expressions of AQP4 in lung tissues of PE and control group were all positive.The strong positive expression signal was detected in the lung tissue of PE group,and the moderate positive expression signal was detected in the lung tissue of the control group.There was statistically significant in IOD values of AQP4 between the two groups(P <0.05);Theexpression of AQP4 in brain tissue of the two groups: moderate positive signal was detected in PE group,and weak positive signal was detected in control group.The difference between the two IOD values of AQP4 were statistically significant(P <0.01).(2)The expressions of P65 in lung tissues of PE group were strongly positive,which were generally positive in the control group;There were significant difference of IOD values between the two groups(P<0.05);P65 was strongly expressed in brain tissue of PE group,and weakly positive in brain tissue of control group.The values of P65 IOD were statistically significant difference between the two groups(P <0.01).(3)The expressions of P65 and AQP4 in lung tissues of PE group were strongly positive.There were significant difference in IOD values between the two groups(P<0.05).The expressions of P65 and AQP4 in the lung tissues of the control group were moderately positive,and the IOD values of that were significantly different(P <0.01).(4)The expressions of P65 and AQP4 in brain tissues were positive in PE group,and the two IOD values of that were statistically significant difference(P <0.05).P65 and AQP4 signals were weakly detected in brain tissues of the control group,and the two IOD values of that were statistically significant difference(P <0.01).Conclusions: The AQP4 and P65 signals were highly detected in brain and lung tissues in the death cases of EV71 infection complicated with neurogenic pulmonary edema,suggesting that AQP4 and P65 may be involved in the formation of neurogenic pulmonary edema induced by EV71.