| Objective:At present,the proportion of infectious diseases caused by virus is bigger and bigger.Because of the virus has stronger pathogenicity,more severe infectivity,higher fatality rate than other microorganisms,and lack of effective means of prevention and control,it has caused some flu disease epidemic,especially the influenza virus.Due to the frequent mutations and antigenic drift of antigenic protein on the surface of the influenza virus,and human body lacks the corresponding antibody,and little immunity humans can be gained through the flu vaccine,all signs indicate that our ability to control the flu today has no difference with 1918.Despite the antiviral drugs and flu vaccine,the world health organization estimates that only in the developed countries,there are 3 million to 5 million serious flu cases and250,000 to 500,000 people death each year,which may be higher in the developing countries.The study has found that severe infection can cause a wide range of pathological injury and serious complications,leading to secondary systemic multiple organ dysfunction(MODS).However,the influenza virus pathogenic mechanism is not fully clear.Hemagglutinin(HA),a kind of glycoprotein exists on the surface of the virus particles,plays an important role in the process of virus infection,is the key factor of pathygenicity of the virus.HA can cause agglutination of red blood cells in vivo and vitro.Studies have shown that influenza virus spread around the body through its agglutination properties,we hypothesized that the agglutination reaction caused by a certain concentration of hemagglutinin is associated with the pathogenicity mechanism of the influenza virus.Therefore,we use phytohemagglutinin(PHA)to induce agglutination reaction in rats,and explore the effect of agglutination on the levels of tissue factor(TF)andD-dimer and IL-6 of the plasma,observe the endothelial cells of rats' pulmonary capillary under the electron microscope,so as to provide a new way to explore the pathogenic mechanism of severe influenza.Methods:All 42 SPF SD rats(male and female unlimited,weight 180-200g),were randomly divided into normal saline control group,different comcentration of PHA groups(5mg/ml,10 mg/ml,20 mg/ml)and corresponding concentrations of inactivated PHA groups,each group of six rats.The normal saline and the different concentration of PHA and inactivated PHA were injected into the rats through the tail vein,dose of 1.5 ml/100 g.10% of chloral hydrate were injected through enterocoelia in order to anesthesia the rats 4 hours after the injection,and then return the inferior vena cava blood.Detect the content of TF,D-dimer and IL-6 of the plasma with ELISA.Observe the morphological changes of endothelial cells of rats' pulmonary capillary under the electron microscope.Results:1.The levels of TF of plasma:The levels of TF of 5 mg/ml,10 mg/ml,20 mg/ml PHA groups were(123.04±35.96)ng/L?(134.67±48.49)ng/L?(132.78±26.29)ng/L respectively,which were significantly higher than that of physiology saline control group(77.28±23.50)ng/L and the corresponding concentrations of inactivated PHA groups(74.65±11.44?79.75±10.70?86.56±9.90)ng/L,the difference was statistically significant(all P < 0.05).Comparing differences between each concentration PHA group has no statistical significance(P > 0.1).The difference was no statistically significant between the physiology saline control group and all the inactivated PHA groups(P > 0.1).2.The levels of D-dimer of plasma:With the PHA concentration of 5 mg/ml,10mg/ml,20 mg/ml,the serum levels of D-dimer were(3.12±0.82)ng/ml ?(2.27±0.74)ng/ml ?(2.77±0.93)ng/ml,which were significantly higher than that of physiologysaline control group(0.57 ± 0.35)ng/ml and all the inactivated PHA groups(0.49 ± 0.25 ? 0.47 ± 0.20 ? 0.48 ± 0.17)ng/ml,all P < 0.05.The difference was no statistically significant between the physiology saline control group and all concentrations of 5 mg/ml,10mg/ml,20 mg/ml of the inactivated PHA groups(all P > 0.1).There was no significant difference in all PHA groups(P > 0.1).3.The levels of IL-6 of plasma:The levels of IL-6 of 5 mg/ml,10 mg/ml,20 mg/ml PHA groups were(29.20±9.87)pg/ml?(26.48±4.82)pg/ml?(26.12±6.00)pg/ml respectively,which were significantly higher than that of physiology saline control group(17.00±2.72)pg/ml and the corresponding concentrations of inactivated PHA groups(17.02±2.54?14.77±1.22?15.07±1.10)pg/ml,the difference was statistically significant(all P < 0.05).Comparing differences between each concentration PHA group has no statistical significance(P > 0.1).The difference was no statistically significant between the physiology saline control group and all the inactivated PHA groups(P > 0.1).4.The morphological characteristics of the endothelial cells of the rats' pulmonary capillary:Compared with the physiology saline control group,the rats' pulmonary capillary endothelial cells were damaged,characterized by endothelial cell swelling,dissolved,cytoplasm osteoporosis,unclear boundary,mitochondria swelling and thick basement membrane,the structure of endothelial cells of all the inactivated PHA groups rats were as normal as the physiology saline control group,the form were flat,border were clear,the structure of organelles were normal and the gas vesides were rich.Conclusion:Agglutination induced by PHA in vivo could damage the pulmonary capillary endothelial cells,cause the blood coagulation and fibrinolysis system dysfunction,which is one of the mechanisms of abnormal bloodcoagulation and fibrinolytic system in virus infection. |
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