| Research Background:In recent years,with the increasing aging of the population,the incidence of stro ke in my country has increased at an annual rate of 8.7%.Among them,dysphagia i s one of the most serious and common sequelae of stroke,and the incidence can be as high as 71%.Coughing,aspiration and aspiration pneumonia caused by dysphagia greatly prolong the hospital stay of patients,not onlly increase the suffering of patient s,but also increase the mortality of patients.At present,there are no specific treatme nts and drugs for stroke in clinic.Western medicine balloon dilatation,gastric tube im plantation and corresponding rehabilitation training can have certain therapeutic effects,but patients suffer great pain and high treatment costs.Traditional Chinese medicine usually uses traditional Chinese medicine orally,acupuncture Fengchi,Tiantu,Acupunc ture points such as Lianquan,or therapies such as "Tongue Three Needles" and "Nap e Three Needles" to treat dysphagia,the treatment effect is good,but due to the char acteristics of the disease itself,which is easy to aspirate,oral administration of traditi onal Chinese medicine has certain risks;acupuncture Acupuncture points are mostly lo cated near the throat,trachea,and large arteries,which are dangerous.Patients are pr one to fear and suffer from poor compliance.Therefore,the above methods have cert ain limitations.The oral spray in the external treatment of traditional Chinese medicin e directly acts on the oropharynx and is absorbed into the blood through the buccal mucosa and sublingual mucosa.This method of administration has been clinically pro ven to be effective and improve clinical symptoms quickly,and is safe and convenien t to use Therefore,the spray of external treatment of traditional Chinese medicine has great advantages in the treatment of dysphagia after stroke.Tongyan spray is compos ed of ginger,Weilingxian and cinnamon.It helps to clear the throat,promote blood c irculation and remove blood stasis,and directly act on the throat and tongue,with dir ect effect and no adverse reactions.It is clinically effective in the treatment of dysph agia after stroke Significantly.At present,the mechanism of Tongyan spray to improv e dysphagia and the key drugs that work are in the exploratory stage,so it is planne d to conduct the experimental research on the disassembly of Tongyan spray from the neuroelectrophysiology of the tongue muscle-hypoglossal nerve conduction system,th e swallowing function,and the neurotransmitter in the hypoglossal nucleus of the swa llowing center,and to provide more data support and basis for its clinical promotion and use.Research Method:(1)48 Wistar male rats,weighing(200-220g),were randomLy divided into sham operation group,model group,ginger+cinnamon group,ginger+weilingxian group,cin namon+weilingxian group,cinnamon+ginger+ Weilingxian group(whole medicine grou p),each group has 8 animals.Except for the sham operation group,the other 5 grou ps used the method of squeezing the right hypoglossal nerve for 30 seconds to establ ish a model.The sham operation group only separated the hypoglossal nerve without clamping.After modeling,each drug group was given the corresponding drugs in the tongue and pharynx.The sham operation group and the model group were given the same amount of deionized water.After 10 minutes of administration,the hypoglossal nerve discharge,the threshold intensity of the tongue muscle,the single contraction a mplitude,The amplitude of tonic contraction,the latency of swallowing and the numb er of swallows caused by distilled water within 30 s,after continuous administration f or 7 days,the above indicators were tested again.The rats tested at the two time poi nts belonged to the same batch.(2)Seven days after the administration,the heart was perfused and fixed,and th e medulla oblongata of the rat was taken to make frozen sections.(3)Nissl staining method to detect the number of neurons in the hypoglossal nuc leus.(4)The enzyme-linked immunosorbent assay was used to detect the expression of substance P(SP)in the serum,and to study the effect of each drug group on the s wallowing reflex.(5)Immunohistochemical staining was used to detect changes in the expression le vels of 5-hydroxytryptamine(5-HT),phosphorylated p38(p-p38),and neuronal nitric o xide synthase(nNOS)in the hypoglossal nucleus after administration.Research result:(1)Neuroelectrophysiological results1)Hypoglossal nerve discharge:After hypoglossal nerve squeezing injury,10 min after administration and 7 days after administration,compared with the sham operati on group at the corresponding time point,the discharge integral area of the model gr oup was significantly reduced(P<0.05));10 minutes after administration,compared w ith the model group,the discharge points area of the ginger+cinnamon group and the whole drug group were significantly increased(P<0.05),and the discharge points of the ginger+weilingxian group and the cinnamon+weilingxian group There was no signi ficant change in the area(P>0.05);after 7 days of administration,compared with the model group,the discharge integral area of the ginger+cinnamon group,ginger+W eilingxian group,cinnamon+Weilingxian group and the whole drug group increased significantly compared with the model group.The nerve discharge area of the ginger+Weilingxian group was significantly higher than that of the whole drug group(P<0.05);compared with 10 min after the administration,the ginger+cinnamon group and the cinnamon+Weilingxian group had The discharge area of the hypoglossal nerve increased significantly(P<0.05).2)Glossal muscle threshold intensity:After hypoglossal nerve squeezing injury,10 min after administration and 7 days after administration,compared with the sham o peration group at the corresponding time point,the tongue muscle threshold intensity of the model group was significantly increased(P<0.05);Compared with the model gr oup at the corresponding time point,the threshold of the tongue muscle of the ginger+cinnamon group,ginger+weilingxian group,cinnamon+weilingxian group and the who le drug group after 10 min and 7 days after administration The intensity was signific antly reduced;compared with 10 minutes after the administration,the tongue muscle t hreshold intensity of the model group was significantly reduced after 7 days of the a dministration(P<0.05)3)Single contraction amplitude of the tongue muscle:After the hypoglossal nerve squeezing injury,10 minutes after administration and 7 days after administration,co mpared with the sham operation group at the corresponding time point,the single con traction amplitude of the tongue muscle in the model group was significantly reduced(P<0.05);10 minutes after the administration,compared with the model group,the si ngle contraction amplitude of the tongue muscles of the ginger+weilingxian group,cin namon+weilingxian group and the whole drug group were significantly increased(P<0.05).There was no significant change in the single contraction amplitude of the tongu e muscle in the ginger+cinnamon group(P>0.05);7 days after administration,compar ed with the model group,the ginger+cinnamon group,the ginger+weilingxian group,t he cinnamon+weilingxian group and the whole group were compared with the model group.The amplitude of single contraction of the tongue muscle in the drug group w as significantly increased(P<0.05).4)Glossary muscle rigidity and contraction amplitude:After hypoglossal nerve co mpression injury,10 min after administration and 7 days after administration,compare d with the sham operation group at the corresponding time point,the tongue muscle rigidity and contraction amplitude of the model group was significantly reduced(P<0.05);10 minutes after the administration,compared with the model group,the single c ontraction amplitude of the tongue muscles of the ginger+weilingxian group,cinnamon+weilingxian group and the whole drug group were significantly increased(P<0.05).T here was no significant change in the tonic contraction amplitude of the tongue muscl e in the ginger+cinnamon group(P>0.05);7 days after the administration,compared with the model group,the ginger+cinnamon group,the ginger+weilingxian group,the cinnamon+weilingxian group and the whole group were compared with the model gro up.The amplitude of tonic contraction of the tongue muscle in the medicine group w as significantly increased(P<0.05).Compared with 10 min after administration,the to ngue muscles of the model group,ginger+cinnamon group,ginger+weilingxian group and cinnamon+weilingxian group had significantly increased tongue muscle contraction amplitudes 7 days after administration(P<0.05).(2)Swallowing function1)Swallowing latency:After hypoglossal nerve compression injury,10 min after administration and 7 days after administration,compared with the sham operation gro up at the corresponding time point,the swallowing latency of the model group was s ignificantly prolonged(P<0.05);After 10 minutes,compared with the model group,th e swallowing latency of the whole drug group,the ginger+cinnamon group,and the g inger+Weilingxian group was significantly shortened,and the swallowing latency of th e cinnamon+Weilingxian group had no significant change(P>0.05);administration 7 D ays later,the swallowing latency of the ginger+cinnamon group,ginger+weilingxian gr oup,cinnamon+weilingxian group and the whole drug group was significantly shortene d(P<0.05).Compared with 10 min after administration,7 days after administration T he swallowing latency of the drug group was significantly shortened(P<0.05).2)Number of swallows:After hypoglossal nerve squeezing injury,10 minutes aft er administration and 7 days after administration,compared with the sham operation g roup at the corresponding time point,the swallowing times of the model group were significantly reduced(P<0.05);After 10 minutes,compared with the model group,the swallowing times of the ginger+cinnamon group,ginger+weilingxian group,and cinna mon+weilingxian group had no significant changes(P>0.05),but the swallowing times of the whole drug group increased significantly(P<0.05);7 days after the administra tion,there was no significant change in swallowing times in the cinnamon+Willingx ian group(P>0.05),and the swallowing times of the ginger+cinnamon group,ginger+Willingxian group and the whole medicine group were significantly increased(P<0.05).3)Substance P:After hypoglossal nerve squeezing injury,the content of substanc e P in the model group was significantly lower than that in the sham operation grou p(P<0.05);7 days after administration,compared with the model group,the whole m edicine group was compared with the ginger+cinnamon group The content of substa nce P increased most obviously,followed by the ginger+Weilingxian group and the ci nnamon+Weilingxian group,with significant differences(P<0.05).(3)Number of Nissl bodiesInjured side:Compared with the sham operation group,the number of Nissl bodi es in the hypoglossal nucleus of the model group decreased after hypoglossal nerve i njury(P<0.05);compared with the model group,the ginger+cinnamon group,cinnamo n+weilingxian group Compared with the whole drug group,the number of Nissl bodie s was significantly increased(P<0.05),and there was no significant change in the gin ger+Weilingxian group(P>0.05);the non-injured side:the number of Nissl bodies i n each group had no significant difference(P>0.05).Only the injured side of the mo del group compared with the non-injured side,the number of Nissl bodies was signifi cantly reduced(P<0.05),and there was no significant difference between the two side s of the other groups.(4)Neurotransmitters in the hypoglossal nucleus:1)5-HT:Injury side:Compared with the sham operation group,the expression of 5-HT in the model group after hypoglossal nerve injury decreased(P<0.05);compare d with the model group,the ginger+cinnamon group,ginger+wei The expression of 5HT in Lingxian,Cinnamon+Weilingxian group and whole medicine group increased si gnificantly(P<0.05).Non-injured side:There was no significant difference in 5-HT ex pression between each group(P>0.05).Only the expression of 5-HT on the injured si de of the model group was significantly lower than that on the non-injured side(P<0.05),and there was no significant difference between the two sides of the other group s(P>0.05).2)p-p38:Injured side:Compared with the sham operation group,the expression of p-p38 in the model group after hypoglossal nerve injury increased(P<0.05);compa red with the model group,the ginger+cinnamon group,ginger+wei The expression of p-p38 in Lingxian,Cinnamon+Weilingxian group and whole medicine group all decrea sed(P<0.05).Non-injured side:There is no significant difference in the expression of p-p38 between each group(P>0.05).Only the expression of p-p38 on the injured sid e in the model group was significantly higher than that on the non-injured side(P<0.05),and there was no significant difference between the two sides of the other group s(P>0.05).3)nNOS:Injury side:Compared with the sham operation group,the expression of nNOS in the model group after hypoglossal nerve injury increased(P<0.05);comp ared with the model group,ginger+cinnamon group,ginger+weilingxian,cinnamon+The expression of nNOS in the Weilingxian group and the whole drug group decrease d(P<0.05).Non-injured side:There was no significant difference in the expression of nNOS between each group(P>0.05).Only the expression of nNOS on the injured si de of the model group was significantly higher than that on the non-injured side(P<0.05),and there was no significant difference between the two sides of the other gro ups(P>0.05).Analysis Conclusion:(1)The model that damages the hypoglossal nerve by clamping and squeezing fo r 30 seconds can prolong the latent period of swallowing in rats,reduce the frequenc y of swallowing,and cause swallowing dysfunction.(2)After hypoglossal nerve injury,give Tongyan spray prescription(full medicine)once,which can enhance the discharge activity of hypoglossal nerve,reduce the thre shold intensity of tongue muscle contraction,enhance the contractility of tongue muscl e,shorten the swallowing latency,and increase Swallowing times can improve swallo wing function;after 7 days of continuous administration,the incubation period of swa llowing can be further shortened.In clinical practice,continuous medication is more e ffective in treating dysphagia.(3)After the disassembly of Tongyan spray,ginger+cinnamon group,ginger+weili ngxian group,cinnamon+weilingxian group all have different degrees of improvement effects on dysphagia.In terms of enhancing the activity of hypoglossal nerve discharg e,ginger+Weilingxian has the best effect,ginger+cinnamon,cinnamon+Weilingxian ha ve the same effect,slightly inferior to ginger+Weilingxian;in terms of enhancing the excitability and contractility of the tongue muscle,the ginger+cinnamon group is the s ame as ginger+Weilingxian.The effect is similar,followed by cinnamon+Willingxian;in terms of enhancing the swallowing function,ginger+cinnamon has the best effe ct,followed by ginger+Willingxian,and cinnamon+Willingxian has limited effect.The results show that in the process of Tongyan spray improving swallowing function,the effects of each drug are ginger>cinnamon>weilingxian,which is compatible with the prescription of ginger as the king medicine and cinnamon and cinnamon as the s ubject medicine.Combination of three drugs has the best effect.(4)The different combinations of Tongyan spray have effects on Nissl body,5-H T,p-p38 and nNOS in the hypoglossal nucleus.The mechanism for improving swallo wing disorders may be as follows:?At the central level of swallowing:Increase the number of Nissl bodies in the hypoglossal nucleus,protect neuron function;inhibit t he activation of p38MApk pathway,reduce inflammation and nerve damage;down-reg ulate the expression of nNOS,reduce the cytotoxic effect of NO production;up-regul ate The expression of the excitatory transmitter 5-HT excites the hypoglossal nerve nu cleus and enhances the innervation of the tongue muscle;?In terms of sensory affer ent:activates the TRPV1 and TRPA1 channels of the sensory nerve endings,enhances the content of substance P,Enhance the swallowing reflex;?In the aspect of exerci se transmission:improve the discharge activity of the hypoglossal nerve,enhance the excitability and contractility of the tongue muscle. |
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