| BackgroundGastrointestinal dysfunction and injury is a common complication in patients with central nervous system diseases.These patients could complain about nausea,vomiting,abdominal distension,dysphoria,and abdominal discomfort.In severe cases,Cushing’s ulcer could appear.This complication is mainly observed in patients who suffer from traumatic brain injury,cerebral tumor,cerebral hemorrhagic/ischemic stroke and other central nervous system lesions,or it could be a serious post-craniocerebral-operational complication.Although people have paid more and more attention to the prevention and treatment of gastrointestinal dysfunction in recent years,there are lacks of more effective intervention methods in clinical practice because of its unclear pathogenesis and the lack of treatments,resulting in poor treatment effect and high morbidity and mortality.A large number of studies have shown that dysregulation of the autonomic nervous system after acute central nervous system injury plays an important role in gastrointestinal dysfunction and injury after traumatic brain injury.It has been reported that amiodarone can inhibit the sympathetic nerve and excite the vagus nerve.Therefore,we measured the pathological changes of the duodenum and the concentration variation of catecholamine(NE),inflammatory factors,in rats with and without the application of amiodarone in rats by intraperitoneal injection after brain injury.In order to explore the relationship between the changes mentioned above and duodenal mucosal injury after brain damage。And we investigate the Protective effects of amiodarone on intestinal tract of rats with acute traumatic brain injufy,so that we can provide reference for the treatment of patients with Cushing’s ulcer after brain injury.Purpose1.To investigate the pathogenesis of gastrointestinal dysfunction and injury in rats after traumatic brain injury;2.To investigate the protective effect of amiodarone on intestinal tract of rats after traumatic brain injury.Methods1.The improved Marmarou method was used to establish the rat model of severe craniocerebral injury;2.SD rats were chosen to be the expreimental subject.The animals were randomly divided into 4 groups: amiodarone group,control group,model group and blank group,with 16 rats in each group.The blank group did not performed with any treatment,and the other groups were established animal models.The amiodarone group was intraperitoneally injected with amiodarone injection(50mg/kg amiodarone mixes with normal saline in 1ml);1ml normal saline was injected intraperitoneally immediately after the establishment of the model in the control group.The model group was not treated after the establishment of the model.According to the different time points,the corresponding experimental animals were killed and the samples were collected.3.The pathological changes of duodenum were observed by optical microscope;Norepinephrine(NE)and inflammatory factors(TNF-α,IL-1β,IL-16,IL-18)in blood and duodenal homogenate of rats were tested by enzyme-linked immunosorbents(ELISA).4.SPSS 25.0 software was used for correlation statistical analysis.Results1.All the models were observed there was a focal brain injury 3mm away from the middle of the brain,with edema and hemorrhage at the lesion site.The duodenal villi of the blank group were intact,upright and orderly.At 72 hours after the brain injury,the duodenal villi structure of the blank group was intact,the lamina propria was arranged neatly,and no obvious inflammatory cell infiltration was observed(HE×100).The duodenal villi were shed and the lamina propria collapsed in the trauma group and the placebo group,with inflammatory cell infiltration(HE×100).The duodenal mucosal structure of amiodarone group was basically complete,part of villi were shed,lamina propria was arranged neatly,and no obvious inflammatory cell infiltration was observed(HE×100).2.Compared with the blank group,the blood NE content of the control group and the model group was significantly increased at 4,24,72 hours and 1 week after modeling(P < 0.05),while there was no significant difference in NE content between the control group and the model group at any time point(P >0.05).Compared with the control group,the content of NE in amiodarone group was significantly decreased at 24 h and 72 h after modeling(P < 0.05).3.Compared with the blank group,NE content of duodenal tissue homogenate supernatant in control group and the model group was significantly increased at 4,24,and 72 hours after establishing model(P < 0.05).No statiscals difference in NE content between the control group and the model group at any time point except 1 week after modeling(P > 0.05).Compared with the control group,the content of NE measured at 4,24 and 72 hours after modeling was significantly lower in the amiodarone group(P < 0.05).4.Compared with the blank group,the blood TNF-α content of the control group and the model group was significantly increased at 24 hours after modeling(P< 0.05),while the results of the control group and the model group were not significantly different from those of the blank group at other time points(P >0.05).There was no significant difference in the level of TNF-α between the control group and the model group at different time points(P > 0.05).TNF-αlevels measured at 24 and 72 hours after modeling were significantly lower in the amiodarone group than in the control group(P < 0.05).5.Compared with the blank group,TNF-α content of duodenal homogenate supernatant in control group and model group was significantly increased at 4and 24 hours after modeling(P < 0.05).There was no significant difference in the level of TNF-α between the control group and the model group at different time points after injury(P > 0.05).Compared with control group,TNF-α content measured at 24 and 72 hours after modeling was significantly lower in amiodarone group(P < 0.05).6.Compared with the blank group,the blood IL-1β content in the control group and the model group was significantly increased at 24 hours,72 hours and 1week after modeling(P < 0.05).There was no significant difference in IL-1βlevels between the control group and the model group at different time points after injury(P > 0.05).Blood IL-1β levels measured at 24 hours after modeling were significantly lower in the amiodarone group than in the control group(P <0.05).7.Compared with the blank group,the content of IL-1β in duodenal homogenate supernatant of control group and model group was significantly increased at 4hours,24 hours,72 hours and 1 week after modeling(P < 0.05).There was no significant difference in IL-1β levels between the control group and model groups at different time points after injury(P > 0.05).IL-1β levels were significantly lower in the amiodarone group than in the control group at both 4and 24 hours after modeling(P < 0.05).8.Compared with the blank group,IL-16 content in blood samples of rats in control group and model group was significantly increased at 24 hours,72 hours and 1week after modeling(P < 0.05).There was no significant difference in IL-1βlevels between the control group and model groups at different time points after injury(P > 0.05).IL-1β levels were significantly lower in the amiodarone group than in the control group at 4,24,and 72 hours after modeling(P < 0.05).9.Compared with the blank group,the content of IL-16 in duodenal homogenate supernatant of rats in control group and model group was significantly increased at 4 h,24 h,72 h and 1 week after modeling(P < 0.05).There was no significant difference in IL-1β levels between the control group and model groups at different time points after injury(P > 0.05).IL-1β levels measured at 24 and 72 h after modeling were significantly lower in the amiodarone group than in the control group(P < 0.05).10.Compared with the blank group,the blood IL-18 content of the control group and the model group was significantly increased at 4 h,24 h,72 h and 1 week after modeling(P < 0.05).There was no significant difference in IL-18 levels between the control group and model groups at different time points after injury(P > 0.05).IL-1β levels measured at 24 and 72 h after modeling were significantly lower in the amiodarone group than in the control group(P < 0.05).11.Compared with the blank group,IL-18 content in duodenal homogenate supernatant of rats in the control group and the model group was significantly increased at 4 h,24 h,72 h and 1 week after modeling(P < 0.05).There was no significant difference in IL-18 levels between the control group and model groups at different time points after injury(P > 0.05).IL-1β levels measured at24 and 72 h after modeling were significantly lower in the amiodarone group than in the control group(P < 0.05).Conclusion1.The massive release of catecholamines and the abnormal anti-inflammatory pathway caused by the abnormal regulation of the autonomic nervous system after acute craniocerebral injury in rats are the important mechanisms of gastrointestinal dysfunction and injury.2.Early intravenous amiodarone injection after acute craniocerebral injury in rats can inhibit the release of catecholamines and pro-inflammatory factors,so as to prevent and treat gastrointestinal dysfunction and injury after traumatic craniocerebral injury. |
