| ［Background］Because the facial nerve is superficial and has long anatomical features,trauma or some iatrogenic injury factors can cause facial nerve damage,leading to partial or complete facial nerve paralysis,which seriously affects people’s daily life.Among them,the most important cause of facial nerve injury is trauma.The facial nerve fracture caused by trauma is generally treated by surgical repair.However,there is a special type of facial paralysis caused by trauma,which is called delayed facial paralysis.Conservative treatment of corticosteroids seems to have achieved a certain effect on the treatment of glucocorticoids to a certain extent.At the same time,many studies have shown that glucocorticoids have a role in all types of facial paralysis.The reason why glucocorticoids can play their role is mainly because glucocorticoids regulate the apoptosis of facial nerve cells through a pathway,and the p38 MAPK pathway is activated in various apoptotic reactions,which is closely related to apoptosis.Important pathway.Our study combines clinical and basic research to explore whether glucocorticoids regulate neuronal apoptosis after facial nerve injury through the p38 MAPK pathway.［Objective ］(1)Clinical observation and discovery of clinical features and outcomes of delayed facial paralysis;(2)Proteomic analysis to find pathways or genes that may affect neuronal apoptosis,differentiation and regeneration after facial nerve injury;(3)It was verified by experiments that the p38 MAPK pathway was involved in the apoptosis of nucleus cells in the posterior facial nerve injury.(4)It was verified that glucocorticoids regulate the apoptosis of facial nucleus cells by inhibiting the p38 MAPK pathway.［Method］The study was divided into three parts:(1)Clinical part of the study:From March 2008 to March 2019,a total of 35 patients with delayed facial paralysis were found in 1620 patients who were admitted to our hospital due to head trauma.To evaluate the facial paralysis level and its recovery in a specific time,to summarize the clinical features and outcomes of delayed facial paralysis after traumatic brain injury;(2)Proteomic analysis of facial nerve nuclei after facial nerve injury: constructing facial nerve squeezing in rats The model was compressed,and the control group was a sham operation group.Three of them were selected from each group.The tissue was then subjected to qualitative and quantitative analysis of the facial nerve nucleus to identify differential proteins,followed by bioinformatics analysis,and R software was used to make volcanoes.Figure and heat map,followed by GO and KEGG enrichment analysis and PPI protein interaction network to find possible gene functions and pathways;(3)Study the role of p38 MAPK pathway in facial nerve injury apoptosis and glucocorticoid Whether the hormone acts on this pathway.Rats were randomly divided into five groups:(1)sham operation group;(2)extrusion model+ saline;(3)extrusion model + glucocorticoid;(4)extrusion model + SB203580;(5)extrusion model + SB203580+ Glucocorticoid were used to evaluate the facial nerve recovery of facial paralysis rats,and the facial nerve function and morphological differences of each group were observed under the electron microscopy.Then,q PCR and Western-Blot were used to detect RNA and protein levels of Caspase3 and Bcl-2,Bax,p38,p-p38 in facial nucleus of rats in each group.Finally HE staining and TUNEL method were used to observe the apoptosis of facial nucleus cells.［Results］(1)Among the 35 patients,18 had facial paralysis on the right side,17 had the same symptoms on the left side;30 patients had different degrees of coma after injury,2 of which were deep coma;the fracture type included longitudinal fracture(17 Cases),transverse fractures(5 cases)and mixed fractures(3 cases);among the 33 patients who underwent conservative treatment,27 patients(81.8%)recovered completely,3 patients(9.1%)returned to grade Ⅱ,and 3 patients(9.1%)returned to grade Ⅲ or Ⅳ.Two patients who underwent surgery were returned to grades Ⅱ and Ⅲ,respectively.(2)Compared with the nucleus of the sham operation group,there are 233 upregulated genes and 11 down-regulated genes in the extrusion models;GO is enriched with 6 molecular functions and 12 biological processes;KEGG enrichment There are 18 meaningful signal pathways.(3)q PCR and Western-Blot results of Bax,Bcl-2 and Caspase3: Bax and Caspase3 gene expression was up-regulated after facial nerve injury,and glucocorticoids and were used to down-regulate the expression of Bax and Caspase3 genes and proteins.Gene and protein expression of Bcl-2.(4)Western-Blot results of p38 and p-p38: group C(extrusion model +glucocorticoid),group D(extrusion model + SB203580)and group E(extrusion model + SB203580 + Glucocorticoids)were significantly down-regulated in RNA and protein expression levels of p38 and p-p38 than group B(extrusion model + saline).(5)HE staining and TUNEL results: in group C(extrusion model +glucocorticoid),group D(extrusion model + SB203580)and group E(extrusion model + SB203580 + glucocorticoid),apoptosis was significantly less than group B(extrusion model + saline).［Conclusion］(1)After head trauma,the incidence of delayed facial paralysis is 2.2%,generally occurring 2 weeks after injury;tibiofibular fractures and ear hemorrhage are more common in patients with delayed facial paralysis after head trauma;After facial trauma,delayed facial paralysis generally does not require decompression surgery,and conservative treatment can achieve better results.(2)p38 MAPK channel may play a major role in neuronal apoptosis after facial nerve injury.(3)Glucocorticoids reduce the apoptosis of nerve cells after facial nerve injury by inhibiting the p38 MAPK pathway,thereby promoting facial nerve function recovery. |
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