The Expression And Significance Of Nerve Cell Apoptosis And Fas/Fas-L MRNA In Cases Infected With EV71

Objective: Patients with severe enterovirus 71(EV71) infection often has nervous system symptoms. In the short term, a few patient can appear serious complications such as pulmonary edema, pulmonary bleeding,and have high fatality rate. But the exact pathogenesis of the neurogenic pulmonary edema is still not clear. Fas is a kind of cell surface receptors, expressed in multiple tissues; FasL is Fas ligand, there mutually combine may pass on the death signals, and leading the nerve cell apoptosis. This may be one of the key factors caused serious complication of the nervous system with infringe by EV71. So this topic first in vivo study the affect of brain cell apoptosis and the expression of Fas and FasL in EV71 infection encephalitis with pulmonary edema or pulmonary hemorrhage in patients. To explore whether in critically ill children with EV71 infection cause brain cell apoptosis and attenuation phenomenon. Provide the theory basis to clarify the mechanism of NPE after EV71 infection. Methods: The clinical data were retrospectively collected from Mar. 2010 to Jun.2013 in seven hospitals in Guilin and the autopsy was performed in 9 children with EV71 infection complicated with neurogenic pulmonary edema, and 7 uninfected EV71 children with pulmonary edema or pulmonary venous pleonaemia who were treated in five hospitals in Guilin at the same time. Tissue samples of major organs such brains,lungs, hearts were test were by HE to observed the pathological features, TUNELmethod to detect apoptosis of cells, expressions of Fas were tested by immunohistochemistry(IHC), and in situ hybridization method to detect Fas mRNA-L. Results:(1) All cases in infection group have nervous system symptoms such as vomiting, startle and limb jitter.(2)HE staining: Pathology examinat of the each organ in infection group, we can see brain with local softening foci and satellite phenomenon, lung visible alveolar cavity collapse and part of the alveolar lumen filled with edema fluid, and there were no obvious abnormal in myocardial tissue. Pathology examinat of the each organ in control group, there were no abnormal visible in brain and myocardial, but in alveolar there were visible pink homogeneous edema fluid in alveolar cavities.(3)TUNEL results: The apoptotic cells were detected in each organ in infection group, positive detection rate of 100. â‘  Comparison in the group between brain, lung, and myocardial tissue: The expression of apoptotic cells in infection group brain became higher, and pairwise comparison with the infection group cardiac muscle and alveolar tissue had a significant difference respectively(P<0.01).There were few apoptotic cells expression in the infection group cardiac muscle and infection group alveolar tissue, so the Apoptosis Index(AI) is low, so no significant differences in both(P>0.05). The contrast group had all discover the apoptotic cell too, but only have a litter, comparison in the group there had no significant difference( p > 0.05). â‘¡ comparison among groups between brain, lung, and myocardial tissue: comparison with infection group, except nerve cell group had a significant difference(P < 0.05), myocardial cell group and pulmonary cpillary endothelial cells group all have no significant differences(P > 0.05).( 4) Fas protein results:â‘ Comparison in the group between brain, lung, and myocardial tissue: The expression of Fas protein in infection group brain became higher, andpairwise comparison with the infection group cardiac muscle and alveolar tissue had a significant difference respectively(P< 0.05); There were few Fas protein expression in the infection group cardiac muscle and infection group alveolar tissue, and no significant differences in both(P>0.05). The contrast group had all discover the Fas protein too, but comparison in the group there had no significant difference( p > 0.05). â‘¡ comparison among groups between brain, lung, and myocardial tissue: comparison with infection group, except nerve cell group had a significant difference(P < 0.05), myocardial cell group and pulmonary cpillary endothelial cells group all have no significant differences(P > 0.05).( 5) FasL mRNA results:In situ hybridization positive signal for brown blue grain, mainly concentrated in the cytoplasm. In situ hybridization detection FasL mRNA and immunohistochemical detection of Fas protein expression have the same changes trend.â‘ Comparison in the group between brain, lung, and myocardial tissue: The expression of FasL mRNA in infection group brain became higher, and pairwise comparison with the infection group cardiac muscle and alveolar tissue had a significant difference respectively(P < 0.05); There were few FasL mRNA expression in the infection group cardiac muscle and infection group alveolar tissue, and no significant differences in both(P>0.05). The contrast group had all discover the FasL mRNA too, but comparison in the group there had no significant difference( p > 0.05). â‘¡ comparison among groups between brain, lung, and myocardial tissue: comparison with infection group, except nerve cell group had a significant difference(P < 0.05), myocardial cell group and pulmonary cpillary endothelial cells group all have no significant differences(P > 0.05).Conclusions: Neurological complications caused by EV71 infection is associated with a large number of nerve cells apoptosis; Course of late in EV71 infection alot of nerve cell apoptosis associated with Fas/Fas- L apoptosis pathway; EV71 infection with hair nerve source pulmonary edema maybe related with the nerve cell apoptosis witch caused by high expression of Fas/Fas-L mRNA...