Intervention Of Jiali Lihuang Decoction On P2X 7 R Inflammatory Pathway In Patients With Sjogren's Syndrome And Anxiety And Depression

Background:Sjogren's syndrome(SS)is a chronic systemic autoimmune disease characterized by lymphocyte infiltration and subsequent dysfunction of exocrine glands,and may lead to the dysfunction in the affected organs and tissues.Patients with SS are often accompanied by symptoms of anxiety and depression,most of which are subthreshold.The precise mechanism of SS remains unclear.Purinergic ligand-gated ion channel 7 receptor(P2X7R)can induce cells to produce and release inflammatory cytokines as well as activate relevant signal pathways to trigger downstream immune reactions.At the same time,it can also affect the function of the central nervous system according to a series of complex reactions.P2X7R may play an important role in the development of SS,and has something to do with anxiety and depression.SS belongs to the category of "dry Bi disease" of traditional Chinese medicine.The type of "yin xu xue yu" is common around SS patients."Yang yin run zao,huo xue qu yu" is one of the most effective treatment for SS with subthreshold anxiety and depression.Modified Baihe Dihuang Decoction also achieved certain effect in the previous clinical experience.Objective:The purpose of this study was to observe the clinical and serological changes of SS with anxiety and depression before and after the intervention of Modified Baihe Dihuang Decoction,so as to clarify the therapeutic effect on patients with SS,and to explore its possible mechanism.Methods:60 patients diagnosed with SS with anxiety and depression were enrolled in this study and were randomized into two groups.The control group was treated with Total Glucosides of White Paeony Capsules,the treatment group combined with the Modified Baihe Dihuang Decoction.The course of treatment was 12 weeks.SS disease activity was assessed by ESSDAI?ESSPRI and TCM syndrome scale.Subthreshold anxiety and depression was assessed using Hospital Anxiety and Depression Scale(HADS).Data concerning general signs and safety indicators?Erythrocyte sedimentation rate(ESR),C-reactive protein(CRP)?immunoglobulin G(IgG)and Salivary gland ultrasonography(SGUS)were also collected.Serum expression of IL-1??IL-6 and TNF-awas evaluated by ELISA.Peripheral blood mononuclear cells(PBMCs)mRNA expression of P2X7R was evaluated by quantitative real-time polymerase chain reaction(qPCR).Data were analyzed by SPSS20.0Results:Sixty patients with SS with anxiety and depression were included.There were two cases off.Both of them came from control group.The total effective cases completed were 58 cases,including 28 cases in the control group and 30 cases in the treatment group.Before treatment,there was no statistical difference in demographic characteristics and clinical characteristics between the two groups of patients.1 Clinical Evaluation of Modified Baihe Dihuang Decoction in SS with Anxiety and Depression PatientsThe scores of TCM syndrome scale,HADS,ESSPRI,ESR,and IgG of the two groups were all decreased after treatment(P<0.05).The reduction of ESRPRI and ESR in the treatment group was significant,compared with the control group(P<0.05).After treatment,CRP decreased in the treatment group(P<0.05).Nimotipine was used to calculate the effective rate.The total effective rates of the treatment group and the control group were 96.67%and 64.29%,respectively.The treatment group improved eye dryness,hot flashes,night sweats,joint swelling and pain,skin arsenal,and constipation scores significantly(P<0.05).The ultrasound scores of salivary glands in both groups did not change significantly before and after treatment(P>0.05).2 Study on Biological Mechanisms of Modified Baihe Dihuang Decoction in SS with Anxiety and Depression PatientsSerum inflammatory cytokines showed a decreasing trend after treatment in both groups.The IL-1? level in the treatment group was lower than before(P<0.05).There was no significant difference in the IL-1? level in the control group(P>0.05).There was no significant difference in IL-6 levels between the two groups after treatment(P>0.05),and there was no significant difference between the two groups(P>0.05).The difference between the two groups in TNF-a before treatment was statistically significant,so TNF-a was not comparable after treatment.The level of TNF-a also showed a downward trend after treatment in both groups,but there was no significant difference in the level of decline(P>0.05).The relative expression of P2X7R mRNA in the two groups was lower than before(P<0.05),but there was no significant difference between the two groups(P>0.05).3 Study on the Safety of Modified Baihe Dihuang Decoction in SS with Anxiety and Depression PatientsBefore treatment,there were 3 patients with mild renal insufficiency in the treatment group,2 mild renal insufficiency and 1 mild liver function abnormality in the control group.After 12 weeks of treatment without revising the original treatment program,the index was reviewed.All eased earlier.There was no obvious abnormality in blood routine(mainly including white blood cell count,neutrophil percentage,red blood cell count,hemoglobin,platelet count)and urine routine before and after treatment in both groups.Conclusion:Modified Baihe Dihuang Decoction has a certain effect on the clinical symptom remission and improvement of serum markers in SS with anxiety and depression Patients,and has no obvious adverse effects on blood routine,urine routine,liver and kidney function.It may reduce IL-1? and other inflammatory cytokines through various mechanisms to inhibit inflammatory responses and improve the effects of anxiety and depression.P2X7R may be one of its targets,but due to the limited sample size,more research is needed to explore its specific mechanism of action.