Study On The Mechanism Of Action Of Traditional Chinese Medicine Combined With Internal And External Treatment To Improve Sebum Metabolism Disorder In Acne With Spleen And Stomach Damp-heat Syndrome Based On The Method Of Separation And Eliminatio

Objective:1.To explore the idea of treating acne with the method of"making evil have a way out"of the method of dispersing,distributing,eliminating and draining of pathogens,in order to provide new ideas and methods for the clinical treatment of acne.2.To observe the clinical efficacy of sanren decoction combined with pomegranate peel polyphenol cream under the guidance of the method of dispersing,distributing,eliminating and draining of pathogens in the treatment of acne with spleen-stomach damp-heat syndrome and its influence on insulin-like growth factor（IGF-1）and apolipoprotein B（Apo B）to apolipoprotein A-1（Apo A-1）ratio.3.To investigate the mechanism of sanren decoction combined with pomegranate peel polyphenol cream on the sebaceous spots of golden hamsters acne model of spleen-stomach damp-heat syndrome.Methods:1.Theoretical research:Based on Professor Ouyang Heng,founder of Huxiang TCM dermatosis school of"analogy thinking",and his theory of"giving the evil way out".It is interpreted that the method of dispersing,distributing,eliminating and draining of pathogens was"seeking outlets for pathogens",regulating Qi activity so that the road for the evil out unblocked,"regulating and treating three Jiao"to"make evil have a way out"on differentiation and drug selection for the treatment of acne,and the treatment will be carried out according to different cases to eliminating and exhausting pathogens or eliminating but not exhausting pathogens,the selected stem hollow Chinese medicine and the developed prescription are listed as evidence.2.Sixty eligible patients were divided into an observation group（30 cases）and a control group（30 cases）according to the random number table.Pomegranate peel polyphenol cream was applied externally in both groups,twice per day.In the observation group,sanren decoction formula granule was provided for oral administration,one dose per day.In the control group,Danggui Kushen pills was taken orally,6 g per time,twice a day.The treatment lasted for four weeks.The Global Acne Grading System（GAGS）score,TCM syndrome score,Children’s Dermatology Life Quality Index（CDLQI）score and Cardiff Acne Disability Index（CADI）score were recorded before and after treatment,followed by the detection of IGF-1level and Apo B/Apo A-1 ratio before and after treatment as well as the safety evaluation.3.Experimental study:32 Golden hamsters were randomly divided into model group,external treatment group with Chinese medicine,internal administration group with Chinese medicine,internal and external treatment group with Chinese medicine,with 8 hamsters in each group.A model of golden hamsters acne of spleen-stomach damp-heat type was constructed by compound factors（fat-sweet diet+external damp-heat environment）.External treatment group with Chinese medicine was given pomegranate peel polyphenols cream for both sides of the sebaceous gland spots（1 g per side each time）;internal administration group with Chinese medicine recieved sanren decoction by intragastric administration(0.56 g·kg^-1);internal and external treatment group with Chinese medicine was given sanren decoction by intragastric administration and pomegranate peel polyphenols cream for both sides of the sebaceous gland spots（the method and dosage were the same as those of external treatment group with Chinese medicine and internal administration group with Chinese medicine）.All interventions were twice per day for 14 d.The general condition,the total area of sebaceous gland spots and histopathological changes of golden hamsters in each group were observed.The non-targeted lipidomic analysis of sebaceous gland spots was carried out using liquid chromatography-tandem mass spectrometry（LC-MS/MS）technology combined with multivariate statistical analysis methods.Results:1.The essence of the method of dispersing,distributing,eliminating and draining of pathogens is to"give the evil way out",it includes seek the right way for the evils out when treat with acne,pay attention on the thinning of qi engine,remove all obstacles in the way of the evil,so that the way of evil is unimpeded.According to the situation,the evil or from the muscle surface to the outside,or to dissolve downward with the bowel movements,or because of regulating qi and blood,or by regulating the zang fu organs,regulating the three jiao,the rashes subside as the evil recedes.2.There were no case shedding during this clinical trial.After treatment,the GAGS,spleen-stomach damp-heat syndrome,CDLQI and CADI scores of the observation group were lower than those of the control group（P<0.05）.The IGF-1 level and Apo B/Apo A-1 ratio of the observation group were decreased as compared with those of the control group（P<0.05）.The overall response rate in clinical symptom alleviation of the observation group was 86.7%（26/30）,which was higher than 60.0%（18/30）of the control group（χ²=29.800,P<0.05）.The overall response rate in spleen-stomach damp-heat syndrome relief of the observation group was 90.0%（27/30）,still higher than 70.0%（21/30）of the control group（χ²=18.167,P<0.05）.No adverse reactions associated with the use of TCM were found.3.The experimental results showed that both the internal and external treatment groups could improve the general condition of golden hamster acne model.Except the model group,the other groups had different degrees of improvement in the pathological damage of sebaceous gland plaque.Compared with the model group,the total area of sebaceous gland plaques in the external treatment group with Chinese medicine and the combined treatment group with Chinese medicine was smaller than before treatment（P<0.05）.Compared with the model group,the metabolism of secondary metabolites lysophosphatidylcholine,lecithin,diglycerol and triglyceride were changed in the external treatment group with Chinese medicine.The metabolism of secondary metabolites lysophosphatidylcholine,lecithin,triglyceride and lysophosphatidylethanolamine were changed in the internal administration group with Chinese medicine.The metabolism of secondary metabolites lysophosphatidylcholine,diglycerol,triglyceride,lysophosphatidylethanolamine,monogalactosyldiglycerol,cardiolipin and sphingomyelin were changed in the internal and external treatment group with Chinese medicine.Under the screening condition of P<0.05,the metabolic pathways with significant differentially enriched metabolites wereα-linolenic acid metabolism,arachidonic acid metabolism and linoleic acid metabolism in the external treatment group with Chinese medicine,the expression of lecithin in these three metabolic pathways was up-regulated.The metabolic pathways with significant differentially enriched metabolites were triglyceride metabolism,α-linolenic acid metabolism,arachidonic acid metabolism and linoleic acid metabolism in the internal group with Chinese medicine,the expression of triacylglycerol was both up-regulated and down-regulated in the triglyceride metabolic pathway,and the expression of lecithin was up-regulated in the other three metabolic pathway.The metabolic pathway with significant differentially enriched metabolites was sphingolipid metabolism in the internal and external treatment group with Chinese medicine,the expression of sphingomyelin in this metabolic pathway was down-regulated.Conclusion:1.Drawing on the valuable experience of the scholars of the past,this paper explores the theoretical connotation of the method of dispersing,distributing,eliminating and draining of pathogens of the warm disease,inherits and creates the application value of the method of dispersing,distributing,eliminating and draining of pathogens for the diagnosis and treatment of acne,and has good practical significance for the understanding and development of the intuitive treatment theory of dermatosis in Huxiang traditional Chinese medicine.2.Sanren decoction combined with pomegranate peel polyphenol cream for acne patients with spleen and stomach dampness-heat syndrome,the two advantages are complementary,can relieve relieve both clinical symptoms and spleen and stomach dampness-heat syndrome,regulate the IGF-1 and Apo B/Apo A-1 ratio level,and improve the quality of life of patients with acne of spleen and stomach dampness-heat syndrome without inducing side effects.3.The curative effect of sanren decoction combined with pomegranate peel polyphenol cream is better than that of single use.The mechanism of the single treatment of pomegranate peel polyphenol cream or sanren decoction on the acne animal model of spleen-stomach damp-heat syndrome was mainly related to the regulation of the metabolism of sebum unsaturated fatty acids（arachidonic acid,linoleic acid andα-linolenic acid）by up-regulating lecithin level.After single treatment with sanren decoction,the expression of triglyceride metabolism in sebum triglyceride metabolism pathway was both up-regulated and down-regulated,suggesting that sanren decoction could regulate sebum metabolism bidirectionally.Lecithin may be used as a potential biomarker of pomegranate peel polyphenol cream or sanren decoction to improve sebum metabolism disorder in acne with spleen-stomach dampness-heat syndrome.The internal and external treatment with Chinese medicine played a role in the treatment of acne mainly by regulating sebum sphingolipin metabolism by down-regulating sphingolipin level.It was speculated that sphingolipin was a potential biomarker for the internal and external treatment with Chinese medicine to improve sebum metabolism disorder of acne with spleen-stomach damp-heat syndrome.