Experimental Study On The Construction Of Severe Heat Stroke Model And Early Renal Pathological Changes And Expression Of Related Inflammatory Factors In Miniature Pigs

BackgroundSevere heat stroke(SHS)is a clinical syndrome caused by central thermoregulation dysfunction.The patients have neurological dysfunction,rhabdomyolysis,disseminated intravascular coagulation((DIC))and multiple organ dysfunction((MODS)).Kidney is an important target organ of multiple organ dysfunction caused by severe heat stroke,and some studies have shown that its injury mechanism may be related to systemic excessive inflammation.Interleukin-1 α(IL-1 α)and tumor necrosis factor-α(TNF-α)have been proved to be pro-inflammatory factors in the early stage of inflammatory reaction,which can promote the occurrence and development of inflammatory reaction,so they can reflect the local inflammatory state of kidney earlier,and their expression level can also directly reflect the degree of inflammatory injury.Available data show that the immune system of large animals is similar to that of humans,in which pigs have more than 80% in common with human immune systems,and pigs are more sensitive to endotoxic shock.In this study,the large animal model of severe heat stroke was established by using miniature pigs as experimental animals,and the pathological changes of kidney tissue and the expression of inflammatory factors IL-1 α and TNF-α in kidney were observed,so as to provide experimental basis for early clinical intervention and treatment of severe heat stroke.Objective1.The large animal model of severe heatstroke was established by using miniature pigs as experimental animals.2.To observe the pathological changes of renal tissue and the expression of related inflammatory factors IL-1 α and TNF-α in kidney.MethodsTwelve 5-month-old healthy male miniature Bama pigs were(CV)grade and weighed10-15 kg.All animals were free of infection and parasites.Blood samples were taken for routine detection.The results showed that blood cell count,blood coagulation function,liver and kidney function and myocardial enzymes were all in the normal range.Twelve experimental pigs were randomly divided into group A(normal control group CK group,),group B(severe heatstroke model group SHS group),6 pigs in each group,and marked respectively(group A: CK-A1,CK-A2,CK-A3,CK-A4,CK-A5,CK-A6;group B:SHS-B1,SHS-B2,SHS-B3,SHS-B4,SHS-B5,SHS-B6).The experimental pigs in group B were put into a constant temperature and humidity box for heat exposure to establish the animal model of severe heat stroke,and the animals in group A were observed at room temperature.after modeling,the experimental pigs in each group were anesthetized,and the pathological sections of kidney tissue were taken to observe the pathological injury,and the histological score of renal injury was scored by Paller score.The levels of serum creatinine(SCr),blood urea nitrogen(BUN)and urinary protein(UP)were determined by celiac vein blood sampling and bladder puncture in group An and B experimental pigs,and the levels of interleukin-1 α(IL-1 α)and tumor necrosis factor-α(TNF-α)in kidney tissue of experimental pigs in group A and B were detected by immunohistochemical(IHC)method.Results1.Changes of core body temperature,conjunctiva and physiological reflex in experimental animals: in SHS group,core body temperature was(43.25 ±0.29)℃,conjunctival congestion,Epididymal reflex and corneal reflex were significantly weakened or disappeared.In CK group,core body temperature was(38.25 ±0.15)℃,conjunctival congestion was not found,Epididymal reflex and corneal reflex were normal.2.The changes of renal function: the levels of serum creatinine,urea nitrogen and urinary protein in SHS group were higher than those in CK group(P < 0.05).3.Renal pathological changes: there was only a small amount of neutrophil infiltration in CK group,and no edema of renal tubules and interstitial space and necrosis of renal tubules were found in SHS group,while severe edema of renal tubules and interstitial space,congestion of renal tubules and glomeruli,neutrophil infiltration,obvious renal tubular necrosis and tubular type were found in SHS group,and the Paller score in SHS group was significantly higher than that in CK group.(P < 0.01).4.Immunohistochemistry: compared with SHS group and CK group,the expression of TNF-α and IL-1 α in SHS group was significantly higher than that in CK group(P <0.01).The positive expression was mainly distributed in Proximal renal tubules.These changes were positively correlated with serum renal injury index and renal tissue pathological injury.Conclusion1.The severe heat stroke model of large animal pigs was successfully established by simulating the environment of high temperature and humidity.2.In experimental animals,renal tissue injury occurs in the early stage of severe heatstroke,which may have a significant impact on the clinical prognosis of severe heat stroke.