| BackgroundSevere heatstroke（SHS）refers to a heat related fatal disease with abnormal central nervous system caused by the imbalance of heat production and heat dissipation in the body under high temperature and humidity environment or violent activities.Its mortality is very high,which is easy to cause systemic inflammatory response syndrome（SIRS）and multiple organ failure（MODS）,such as neurological deficit,cardiovascular failure,liver failure and renal failure.Coagulation dysfunction is a common complication of severe heatstroke.In severe cases,it can develop into disseminated intravascular coagulation（DIC）,which is one of the main risk factors of severe heatstroke death.Studies have shown that vascular endothelial lesions play a key role in the coagulation dysfunction caused by severe heatstroke,and are the most important feature of the pathophysiology of coagulation dysfunction related to heat stroke.Intercellular adhesion molecule-1（ICAM-1）is an inflammatory mediator,which is mainly expressed on vascular endothelial cells.At the same time,it is also a specific marker of vascular endothelial cell injury.At present,there are few reports on vascular endothelial cell injury associated with severe heatstroke in high temperature and humidity environment at home and abroad.This study was based on the establishment of pig severe heatstroke model in the constant temperature and humidity climate cabin of our hospital to analyze the functional changes and corresponding characteristics of vascular endothelial cell injury in severe heatstroke pigs,in order to provide a theoretical basis for strengthening the protection of vascular endothelial cell injury and early anticoagulation in clinical severe heatstroke.ObjectiveTo observe the pathological changes of vascular endothelial cell injury and the expression of intercellular adhesion molecule-1 in heat radiation diseased pigs.MethodSelect Twelve CV healthy male Bama miniature pigs,weighing 15-20 kg and aged from 4 to 5 months,were randomly divided into normal temperature control group（NC group,6）and severe heatstroke group（SHS group,6）.Referring to the establishment of severe heatstroke pig model under high temperature and high humidity environment in the early stage of our research group,all animals were induced by general anesthesia after fasting water for 12 hours and placed in constant temperature and humidity climate cabin,while NC group was placed in normal temperature environment（temperature 35-37℃ and relative humidity 65±5%）;SHS group was placed in high temperature environment（temperature 44-47℃,relative humidity 65±5%）.Internal jugular vein blood samples were collected from normal temperature control group and severe heatstroke group before and after the experiment,and sent for prothrombin time（PT）,activated partial thromboplastin time（APTT）,plasma D-Dimer（D-DI）and fibrinogen degradation product（FDP）and blood cell count.After the experiment,the rats were killed under anesthesia.The abdominal aorta,coronary artery and lung tissue samples at the same site were taken.The pathological changes of abdominal aorta,coronary artery and lung were observed by hematoxylin eosin staining（HE）.Immunohistochemical staining（IHC）was used to observe the level of intercellular adhesion molecule-1（ICAM-1）in normal temperature control group and severe heatstroke group.The ultrastructural changes of coronary artery and pulmonary microvessel were observed by high-power projection electron microscope.Results1.Changes of coagulation function: There was no significant difference in coagulation function between normal temperature control group and heat radiation disease group before experiment（P > 0.05）.There was no significant difference in activated partial thromboplastin time,prothrombin time,plasma D-dimer,fibrinogen degradation products and platelet count in NC group before and after the experiment（P > 0.05）;After the experiment,the activated partial thromboplastin time,prothrombin time,plasma D-dimer and platelet count in SHS group were higher than those before the experiment and higher than those in NC group（P < 0.05）.2.Pathological changes of vascular endothelial cells: No obvious pathological changes were observed in abdominal aorta,coronary artery and lung tissue under light microscope in normal temperature control group.Light microscopic observation of abdominal aorta in SHS group showed that the structure of abdominal aorta was slightly abnormal,arterial wall spasm,elastic fiber spasm and obvious contraction,endothelial cells were slightly edema,degeneration and no necrosis,and there was no obvious inflammatory cell infiltration.Coronary artery in SHS group: abnormal coronary artery structure,spasm of coronary artery wall,spasm and obvious contraction of elastic fibers,surrounding cellular edema,dilation and bleeding of nutrient vessels,accompanied by massive bleeding around,small number of endothelial cells,disorder and fracture of smooth muscle layer,and no obvious inflammatory cell infiltration.Pulmonary microvessels in SHS group: the structure of lung tissue was obviously abnormal,the capillaries in alveolar wall dilated and bled,most small blood vessels congested,a large number of vacuoles formed in the cavity,pulmonary septum thickened,protein thrombosis in small blood vessels,diffuse bleeding in the alveoli and pulmonary interstitium,accompanied by a small amount of inflammatory cell infiltration,and the number of endothelial cells in the lumen was significantly reduced,shed and necrotic,surrounded by vacuoles,edema Degeneration,necrosis and massive bleeding.3.Immunohistochemical results: The normal temperature control group showed positive expression of ICAM-1 in abdominal aorta,coronary artery and lung tissues,and a large number of endothelial cells were stained with serosa,showing dark brown granules or even continuous dark brown lines.ICAM-1 was weakly positive in abdominal aorta,coronary artery and lung tissues in the heat radiation disease group,and only a small number of endothelial cells were weakly positive in light yellow.The average optical density of ICAM-1 in vascular tissue in SHS group was lower than that in NC group（P <0.05）.4.Ultrastructural changes of tissues were observed by transmission electron microscopy: Under different magnification,irregular nuclear shape,mitochondrial swelling,mitochondrial vacuolar degeneration and mitochondria with complete structure were observed in the lungs of the SHS group.Capillary endothelial cells were arranged in parallel with the alveolar wall,and the alveolar septum was clearly visible.In the SHS group,the coronary arteries are seen at different magnifications with a small number of nuclei in different shapes and swelling of mitochondria.Conclusion1.The blood vessels of experimental animals and pigs were damaged by heat radiation disease,and the damage of small blood vessels and microvessels was significant.2.The pathological changes of endothelial cells and the abnormal expression of intercellular adhesion molecule-1 in the early stage of heat radiation disease are one of the important mechanisms of vascular endothelial cell injury. |
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