| ObjectiveOn the basis of literature analysis and theoretical research,the core pathogenesis and general treatment principles of motion sickness were preliminarily clarified,and the relevant theory of treating motion sickness from spleen and stomach was further improved;to prove the correlation between TCM constitution and susceptibility to motion sickness through retrospective investigation of epidemiology,we provide evidence for the treatment of motion sickness from the theory of spleen and stomach;a rat model of motion sickness established,we evaluate the pharmacodynamic effect of the Zhiyunxiedingfang(ZYXDF),and identify the chemical components and clarify the chemical substance basis of ZYXDF;through the methods of metabonomics and network pharmacology,the biological markers of motion sickness and the main pharmacological mechanism of anti-motion sickness prescription were preliminarily explained,and the biological mechanism of ZYXDF in treating motion sickness from the theory of spleen and stomach was discussed,which provided scientific support for the clinical application and promotion of ZYXDF.MethodsLiterature research:Comprehensively sort out the clinical literature of Chinese medicine for the treatment of motion sickness,and conduct cluster statistical analysis based on the prescriptions selected by the excluded exclusion criteria,comb the prescriptions and traditional Chinese medicines for clinical treatment of motion sickness,explore the medication rules for prevention and treatment of this disease,and summarize the motion sickness general rule.Use drugs to prove,reverse speculate the core pathogenesis of motion sickness and the main types of syndromes.Theoretic study:Through the examination of ancient literature records,the theoretical basis and connotation of treating motion sickness from the spleen and stomach are explored.Retrieving relevant literatures at home and abroad,demonstrating that the treatment of motion sickness from the spleen and stomach meets the clinical prevention and treatment ideas,and explores the correlation between spleen and stomach and pancreatic secretion.Clinical research:The whole group of 300 escort troops was selected.Standardized TCM Constitution Questionnaire and Revised Motion Sickness Susceptibility Questionnaire and Seasickness Questionnaire were used to analyze related investigation of the situation of the TCM constitution distribution,the susceptibility distribution of motion sickness and degree of seasickness..And we research on four related aspects of escort troops,including the correlation between TCM constitution and susceptibility to motion sickness,the correlation between TCM constitution and the degree of seasickness,and the distribution of seasickness and susceptibility to motion sickness,the degree of seasickness of escort troops is compared under different physical conditions and different susceptibility to motion sickness.Experimental research:(1)Establish a rat model of motion sickness.After 3 days of pre-dose,the model was simulated by biaxial rotational acceleration for 2 hours,and the behavioral indexes of rats(motion sickness index,total spontaneous activity distance and activity time)were observed,and the use of neurotransmitter indicators(vestibular nucleus,plasma acetylcholine and histamine content)to verify the efficacy of anti-motion sickness;(2)The chemical composition of ZYXDF was identified by UHPLC-Q-TOF-MS to clarify its chemical basis.(3)Based on the pharmacodynamics study,the GC-MS method was used to analyze the serum metabolomics of rats,and the biomarkers of motion sickness were preliminarily analyzed,and the differential metabolites that could be regulated by ZYXDF were screened;(4)Combining the results of the chemical substance basis and metabolomics research of ZYXDF,through the network pharmacology method,we explore the relevant target proteins for the anti-halation action of ZYXDF,and associate it with the differential metabolites and enrich the pathway.To construct a network of "ingredient-target protein-metabolite-related protein-metabolites",we preliminarily explain the pharmacological mechanism of anti-motion sickness;(5)Enzyme-linked immunosorbent assay and radioimmunoassay were used to detect the levels of insulin,glucagon,epinephrine and leptin hormone in the serum of each group.And we further preliminary verify the results of metabolomics and network pharmacology.Therefore,it reveals the mechanism of anti-stun effect by regulating the blood sugar level of rats under the guidance of traditional Chinese medicine theory from the treatment of spleen and stomach.ResultsLiterature research:Through the statistical analysis of the frequency of drug occurrence,the core pathogenesis of motion sickness in the reverse direction is "spleen and stomach weakness,transport disorders".Through the cluster analysis of the prescription drugs used in the literature,it was found that Ginger,Tangerine peel,Poria cocos and Atractylodes were the core drugs for the prevention and treatment of motion sickness.It is speculated that the spleen and stomach qi deficiency and phlegm-dampness resistance are the most common syndromes of motion sickness.The therapeutic effect of the drug is mainly in the aspects of strengthening the spleen and replenishing qi,drying the wetness-evil and eliminating phlegm,delaying vomiting in warming,activating qi for lowering adverse qi,and calming the liver.Four basic prescriptions are decoction for Dissipating Humidity and Promoting Qi and Warming to Stop Vomiting strengthening the spleen and replenishing qi,tranquilizing by nourishing the heart,suppressing hyperactive liver for calming endogenous wind,clearing damp and promoting diuresis,wuling san.Theoretic study:"Spleen and stomach weakness,transport disorders" is the cause of motion sickness,and the elevated blood sugar produced by motion sickness is closely related to the theory of "qi of spleen cannot transmit nutrients to the whole body.",so we regulate blood sugar levels and relieve gastrointestinal symptoms of motion sickness by promoting insulin secretion.The symptoms of gastrointestinal reflect the train of treatment thought of spleen and stomach treatment of motion sickness.Clinical research:(1)Among the biased constitutions of long-distance naval crew,the first three are Qi deficiency(11.97%),damp-heat(10.26%)and phlegm-dampness(5.98%);(2)Among the 234 crew members who met the standard of the row in this study,the crew members has susceptibility to mild,moderate,and severe motion sickness accounted for 36.32%,41.03%,and 22.65%,respectively.The influence of the position on the susceptibility of the crew member to motion sickness is different.The officer is more susceptible to motion sickness than the warrior.The difference is statistically significant(P<0.01)and has a positive correlation(r=0.187,P=0.004).The degree of education,age,military age,and BMI had no effect on the susceptibility scores of long-lived crew members’motion sickness,and the differences were not statistically significant(P>0.05);(3)234 long-ship crew members were in the same class of waves,21 cases(8.97%)were not seasick,50 cases(21.37%)were mild seasickness,51 cases(21.79%)were moderate seasickness,and 22 cases were severe seasickness(9.40%),there were 90 cases(38.46%)of seasickness disease,but the grade,education level,age,military age,and BMI had no effect on the seasickness of long-haul crew members,and the difference was not statistically significant(P>0.05);(4)Among the long-lived crew members with mild,moderate,and severe motion sickness susceptibility,the top three Chinese medicine physiques were peaceful(70.59%,52.08%,41.51%)and qi deficiency(10.59%,12.50%,13.21%),damp heat(7.06%,12.50%,11.32%),of which the proportion of damp-heat disease and dampness in the susceptibility to severe motion sickness was 11.32%.Susceptibility to motion sickness was positively correlated with phlegm-dampness(r=0.731,P=0.003);(5)Qi deficiency,damp heat and phlegmatic hygrosis are also the three biased physiques most likely to cause seasickness;(6)The susceptibility to motion sickness was positively correlated with the degree of seasickness(r=0.370,P=0.000).(7)The susceptibility to motion sickness was significantly different for the effects of peace and phlegm on seasickness(P<0.01;P<0.05).Experimental study:(1)In behavioral aspects:motion sickness index,total spontaneous activity distance and activity time in model group were significantly higher than of that normal group(P<0.001;P<0.01;P<0.001);the motion sickness index of medium and high doses was lower than the model group(P<0.05;P<0.01),and the total distance and activity time of spontaneous activity were higher than that of the model group(P<0.05,P<0.001;P<0.05,P<0.001).The levels of acetylcholine and histamine in the vestibular nucleus and plasma of the model group were significantly higher than those in the normal group(P<0.05;P<0.001).The content of acetylcholine and histamine in the vestibular nucleus and plasma in dose group of ZYXDF was significantly lower than the model group(P<0.05);(2)The chemical composition of ZYXDF was compared with 490 compounds in the known chemical composition database,and some amino acids and fatty acid compounds were eliminated,and a total of 122 chemical components were identified.(3)Each dose group of ZYXDF could up-regulate 89 differential metabolites induced by the model group.And the differential metabolites are up-regulated after treatment with each dose of ZYXDF are pyruvate,proline and methionine.(4)The results of network pharmacology showed that ZYXDF may achieve the effect of preventing motion sickness by regulating the metabolism of arachidonic acid.(5)The expression of insulin,glucagon,epinephrine and leptin hormone in serum of motion sickness rats with anti-motion sickness prescription intervention tends to be normal.ConclusionBased on the above studies,it is found that "spleen and stomach weakness,transport disorders"is the cause of motion sickness,and the elevated blood sugar produced by motion sickness is closely related to the theory of "qi of spleen cannot transmit nutrients to the whole body.".The stagnation of the crew with qi deficiency,damp heat and phlegmatic hygrosis is higher,indicating that it may be more prone to motion sickness.The treatment of spleen and qi,dampness and phlegm,and anti-reverse vomiting are the principles of spleen and stomach,and the treatment of motion sickness from the spleen and stomach meets its basic pathogenesis.Experimental studies have confirmed that ZYXDF could prevent or alleviate the motion sickness of motion sickness rats,and it is reflected by spontaneous activity experiments that ZYXDF does not produce adverse reactions such as mental fatigue and other central inhibition.ZYXDF could inhibit the release of acetylcholine and histamine neurotransmitters,which is also evidence of its anti-corona effect.The expression of insulin,glucagon,epinephrine and leptin hormone in the serum of motion sickness rats treated with the stagnation protocol was normal,indicating that ZYXDF of strengthening the spleen and replenishing qi and eliminating dampness and eliminating phlegm,downbear counterflow and check vomiting could promote the secretion of insulin and maintain the stability of blood sugar through the metabolic pathway of arachidonic acid,so as to achieve the effect of anti-motion. |
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