Explore The Mechanism Of The Adrenaline Through Pulmonary C-fibers Lead To Secondary Pulmonary Injury After Acute Spinal Cord Injury In Rats

PART?THE CONSTRUCTION OF A MODIFIED ANIMAL MODEL FOR LOWER THORACIC SPINAL CORD INJURY AND THE MECHANISM OF SECONDARY PULMONARY INJURYObjective: Acute spinal cord injury is a common surgical emergency and critical illness,which could affect the quality of life of patients and threaten their health seriously.The most common complication following ASCI is respiratory disease.Currently,the causes of respiratory complications after ASCI are still unclear and controversial.To determine whether secondary pulmonary injury is common after ASCI,we established an animal model for lower thoracic ASCI by modifying Allen's method.Methods: The rats were divided into sham operation group and SCI group randomly and each group was subdivided into 7 subgroups according to the hitting time of 6h?12h?1d?3d?1w?2w?4w.In the injury group,ASCI were induced at the level of the tenth thoracic vertebra by a modified Allen's method.Rats were sacrificed at different timing after surgery.Pulmonary edema was assessed by calculating the ratio of the wet-to-dry lung weight(W: D).Pulmonary edema and hemorrhage were evaluated by observing gross and microscopic morphology.Results: In the injury group,gross morphologic observations showed hemorrhagic lesions on the lung tissue 12 hours after ASCI and pulmonary edema 24 hours after ASCI.Pulmonary edema peaked 3 days after ASCI and was obviously decreased 1 week after ASCI.Hemorrhage returned to normal until 2 weeks after ASCI.While in the sham surgery group,there was no pulmonary tissue hemorrhage and edema.HE staining showed congestion of pulmonary capillaries 6 hours after ASCI.The pulmonary alveoli were filled with erythrocytes and serous extravasate 12 hours after ASCI.Hemorrhage and edema were observed in the interstitium and lung alveoli 24 hours after ASCI.The lung W/D of the ASCI group was significantly higher than that of the sham operation group,and edema was most significant 3 days after injury.Conclusion: Early pathologic changes such as pulmonary congestion,hemorrhage,and edema after injury may be the basis for early respiratory dysfunction following ASCI.PART ? THE MECHANISM OF ADRENALIN IN THE SECONDARY LUNG INJURY AFTER ACUTE SPINAL CORD INJURY IN RATSObjective: In the first part,we established the rat ASCI model and confirmed that ASCI would induce secondary lung injury in rats.Epinephrine is the main hormone secreted by adrenal medulla and played an important role in producing stress response.Some studies have shown that epinephrine can affect the activity of type C fibers in the lungs,leading to pathological changes,and can also affect the activity of ion channels with other stimulants.Therefore,we speculated that epinephrine may be involved in the pathological process of lung injury secondary to ASCI in rats.On the basis of the above studies,this research mainly discusses the possible mechanism of lung injury secondary to ASCI in rats,and determines whether epinephrine is involved in lung injury secondary to ASCI in rats.Methods: After detecting the levels of epinephrine and norepinephrine in rats after ASCI,the changes of the two hormones after ASCI were clarified and the hormones that might be involved in the pathological process were identified.Rats were divided into sham operation group,bilateral adrenal gland excision group and bilateral adrenal gland ASCI group,and the ASCI model of bilateral adrenal gland excision in rats was established.After blocking epinephrine in rats,HE staining was used to observe the pathological changes of lung tissues after adrenalectomy in rats after ASCI,and W/D was applied to evaluate the pulmonary edema in rats.Meanwhile,the expression of TRPVI and substance P in the lung tissues of rats was detected to identify the direct causes of lung injury mediated by them.Results: TRPV1 and SP expression levels in lung tissues of rats after ASCI were significantly higher than those in the sham group.After the removal of bilateral adrenal glands,TRPV1 and SP expression levels in lung tissues of rats were significantly lower than those in the ASCI group.The pathological changes such as hemorrhage and edema in the lung tissue of the ASCI group after bilateral adrenal gland resection were also significantly reduced compared with the simple spinal cord injury group.Conclusion: Epinephrine plays a key role in the secondary lung injury after ASCI in rats.The mechanism is to activate the middle and lower TRPV1 ion channel of lung tissue,promote SP release and lead to subsequent inflammatory response and secondary lung injury.PART ? THE ROLE AND MECHANISM OF PCFS IN SECONDARY LUNG INJURY AFTER ACUTE SPINAL CORD INJURY IN RATSObjective: PCFs is the main afferent sensory nerve of respiratory tract,which can activate the ion channel on the surface of PCFs when stimulated by irritants or endogenous inflammatory mediators,leading to the activation of PCFs.Activated PCFs can release a large amount of inflammatory mediators and neuropeptide SP,etc.PCFs play an important role in respiratory diseases and acute lung injury.In the previous part of the experiment,we found that the direct factor leading to the secondary lung injury after ASCI in rats was the release of a large number of SP.Since the main source of SP in the lung was activated PCFs,we speculated that PCFs was also involved in the pathological process of secondary lung injury,which might be the downstream channel of adrenaline.The purpose of this study was to determine whether PCFs was involved in the pathological process of lung injury secondary to ASCI in rats,and to preliminarily explore its possible mechanism and signal pathway.Methods: Adult rats were divided into sham group,blank control group and ASCI group after high-dose pretreatment with capsaicin.Capsaicin group was treated with a large dose of capsaicin to completely inhibit PCFs,while the blank control group was treated with the same mixed solution without capsaicin.Pathological changes such as pulmonary hemorrhage and edema after ASCI were detected in each group and changes in SP expression in lung tissues were also detected.Results: The pathological changes of pulmonary hemorrhage and edema in capsaicin group after ASCI were significantly reduced compared with the blank control group,but were still markedly increased compared with the sham operation group.SP expression in lung tissues of rats in capsaicin group was also lower than that in the blank control group,but still higher than that in the sham operation group.Conclusion: PCFs is involved in the pathological process of lung injury secondary to ASCI in rats and plays a major role in mediating lung injury.Lung injury secondary to ASCI in rats is a multi-factor,multi-pathway and complex pathological process.