Based On Metabolomics To Explore The Effect Of "kaixuan Detoxification, Invigorating Kidney And Cultivating Yuan" Method On Lipid Metabolism In Psoriasis

ObjectiveTo explore the efficacy and safety of "opening pore and detoxifying,tonifying the kidney and vitality"(Kaixuan Bushen)method in treating psoriasis through clinical observation and to observe the effect of Kaixuan Bushen method on lipid metabolism in psoriasis patients by targeted lipidomics,aiming to find the internal relationship of "Kaixuan Bushen method-lipid metabolism disorder-pathological phenotype" and provide theoretical basis and support for Kaixuan Bushen method in the treatment of psoriasis.MethodsStudy 1:This research adopted the self-pre-and post-control and blank control method.Patients with psoriasis who had been admitted to the Dermatology Clinic of Guang’anmen Hospital from September 2019 to November 2020 and met the inclusion criteria were recruited.The basic information,manifestations of skin lesions,prescriptions and examinations of patients were recorded by questionnaires and telephone interviews for 12 weeks to evaluate the clinical efficacy and safety of the Kaixuan Bushen method.At the same time,the biochemical test results of 30 healthy volunteers were collected by physical examination in the Prevention and Health Care Department of Guang’anmen Hospital as control to explore the regulatory effect of the Kaixuan Bushen method on blood lipids in psoriasis patients.Study 2:The high-performance liquid chromatography-tandem mass spectrometry metabolomics technology(UPLC-MS)was employed,and the LC-(±)ESI-MS spectrums were obtained using multiple reaction monitoring(MRM)mode at positive and negative ion status.After using Masslynx for peak extraction on these spectrums,the peak area was imported into SIMCA-P software(Version 14.1)for principal component analysis(PCA)and orthogonal partial least square discriminant analysis(OPLS-DA)to screen differential metabolites among the groups.The correlation analysis was carried out by R(Version 4.0.2),and the differential metabolites were identified by comparing the mass-charge ratio of mass to charge ratio m/z or accurate molecular weight of mass spectrometry using the online database(https://www.lipidmaps.org/).ResultsStudy 1:A total of 32 patients with psoriasis(20 males and 12 females)were recruited in the study,and 30 healthy volunteers(19 males and 11 females)were recruited as controls.Because 6 patients refused to be collected blood samples after treatment,their post-treatment biochemical test results were not available.1)The average BMI of psoriasis patients is 24.6 ± 0.63 kg/m2,which was higher than that of healthy people with a significant statistical diffrence(P<0.05).A total of 10 people in the psoriasis group reached the standard of overweight and obesity(BMI≥24 kg/m2),accounting for 31.25%of the psoriasis group.2)As for the biochemical indexes,compared with healthy people(n=30),patients with psoriasis(n=32)had lower level of high-density lipoprotein cholesterol(HDL-C)with a significant difference(P<0.05).Though the difference was not statistically significant,the level of cholesterol(CHO),triglyceride(TG),and low-density lipoprotein(LDL-C)showed an upward trend in the psoriasis group comparing with the control.3)After treating with the method for 12 weeks,the Psoriasis area and severity index(PASI)score of the psoriasis patients(n=32)were significantly reduced with a statistical difference(P<0.0001)and the effectual rate(PASI75)reached 66.87%.The VAS score for itching was significantly reduced with significant difference(P<0.0001).No significant abnormal parameters were observed among the blood routine test,urine routine test,liver function test and kidney function test and no adverse events were reported during the treatment.4)After the treatment,the levels of CHO(P=0.079),TG(P=0.211),and LDL-C(P=0.133)of psoriasis patients(n=26)showed a downward trend and the level of HDL-C(P=0.331)showed an upward trend,though the differences were not statistically significant.Study 2:A total of 30 healthy serum samples,26 pre-treatment serum samples,and 26 post-treatment serum samples were analyzed using UPLC-MS targeted lipidomics.The results were as follows:1)The lipid metabolism profiles of patients with psoriasis(n=26)and healthy individuals(n=30)were significantly different.There were 36 different metabolites(34 species in positive ion mode,2 species in negative ion mode),including triacylglycerol(TAG,n=19),free fatty acid(FFA,n=2),ceramide(Cer,n=5),sphingomyelin(SM,n=1),phosphatidylcholine(PC,n=3),phosphatidylethanolamine(PE,n=6).All the metabolites expressed highly in the psoriasis group except for FA 25:0.2)In the correlation analysis between significantly different metabolites and PASI score,the stearidienic acid(FA 18:2)was positively correlated with the severity of psoriasis.3)After the treatment of the Kaixuan Bushen method,the metabolic profile of psoriasis patients shifted to healthy people.Palmitic acid(FA 16:0)and stearic acid(FA 18:0)were significantly different between the two groups,the expression levels of which showed an upward trend in psoriasis patients compared with control,with no significant difference.However,the expression levels of these two metabolites decreased significantly after treatment.4)Applying PASI75 as standard to divide psoriasis patients into effective group(n=18)and ineffective group(n=8),a total of five different metabolites were identified between the two groups,namely TAG 48:1,TAG 48:2,TAG 48:3,TAG 50:2 and TAG 50 TAG 3.The prediction model of curative effect was established based on the five markers with 88.5%of prediction accuracy and 1 of AUC value.Conclusion:This study revealed that there were lipid disorders in psoriasis patients,mainly"lipid accumulation".The "opening pore and detoxifying,tonifying the kidney and vitality"method might treat psoriasis skin lesions by improving lipid metabolism disorders,which mainly reflected in the regulation of saturated fatty acid metabolism.