| Sjogren’s syndronm(SS)is a disease of autoimmune balance disorder,which is characterized by the damage of the structure and function of exocrine glands including salivary glands,lacrimal glands and so on,and a large amounts of lymphocyte infiltration can be observed in tissue.The clinical manifestations of SS mainly include dry mouth,dry eyes,dry skin,etc.Besides,SS can also cause the damage of systemic multisystem.SS is divided into Primary sjogren’s syndrome(pSS)and Secondary sjogren’s syndrome(sSS),and sSS can be accompanied by complications of other rheumatoid immune diseases,such as Rheumatoid arthritis and systemic lupus erythematosus.It is found that the immune inflammatory and neurotoxic damage of exocrine glands is important to the pathogenesis of SS,and the suppression of inflammatory and neurotoxic damage of exocrine glands is a new direction for the treatment of the disease.AMPK is an important anti-inflammatory factors.After AMPK is activated,it can inhibit the immune inflammatory response by activating the PPARy transcription to inhibit the NF-κb、AP-1、STAT-1 and other signaling pathways.So the AMPK is an important molecular to inhibits the immune inflammatory injury caused by SS.Banxia Qinlian Decoction is an empirical prescription used by my mentor to treat SS,it has the function,of improving the circular motion of Qi,clearing damp and turbidity,and has a remarkable clinical effect.This paper discusses the molecular mechanism of Banxia Qinlian Decoction that improve the immune inflammatory damage in exocrine gland which caused by SS and the treatment of clinical efficacy of SS,from the analysis of animal experiment and clinical efficacy,and provides a new way to treat SS.1.Experimental study.Objective:To observe the effect of Banxia Qinlian Decoction on the expression of AMPK:PPAR-γ:IL-17:AQP5 protein in the submandibular gland of NOD mice.Methods:Six BALB/c mice were set as normal group.The 24 female NOD mice were randomly divided into model group,positive drug group,Chinese medicine double dose group and conventional dose group after 4 weeks of adaptive feeding,each group had 6 mice.The blank control group and the model group were treated with normal saline with the dosage of 10 mL·kg-1·d-1 by gavage.The positive drug group was treated with glucosidorum tripterygll totorum with the dosage of 10mg·kg-1·d-1 by gavage.This dose is equivalent to 10 times the average clinical dose.Chinese medicine double dose group and conventional dose group were treated with Banxia Qinlian Decoction with the dosage of 40g·kg-1·d-1 and 20g·kg-1·d-1 by gavage respectively,which are calculated by the amount of raw medicine.These doses equivalent to 20 and l0times the average clinical dose respectively.After 12 weeks of continuous treatment,the bilateral submandibular gland tissues of mice were taken and fixed with a 10%concentration of the neutral buffered formalin solution,followed by paraffin embedding.The protein expression levels of AMPK α1、AMPK α2、PPARγ、IL-17 and AQP5 in the submandibular gland tissues of mice were detected by immunohistochemistry.Results:Compared with the normal group,the protein expression of AMPKα1、AMPKα2 and PPARy in the model group was decreased(P<0.05,P<0.01).The expression level of IL-17 protein was significantly increased(P<0.05).The expression level of AQP5 protein was significantly increased,mainly expressed in the basement membrane(P<0.01).Compared with the model group,there was no significant change in the expression of AMPKα1 protein in the positive drug group,Chinese medicine double dose group and conventional dose group,and the difference was also not statistically significant(P>0.05).In the positive drug group,Chinese medicine double dose group and conventional dose group,the expression level of AMPKa2 protein showed an increasing trend,but the difference was also not statistically significant(P>0.05).The expression level of PPARy protein was significantly increased,the difference was statistically significant(P<0.05,P<0.01).The expression level of IL-17 protein was significantly decreased in the positive drug group and the Chinese medicine double dose group,the difference was statistically significant(P<0.05,P<0.01).In conventional dose group,the expression level of IL-1 7 protein showed an decreasing trend,but the difference was not statistically significant(P>0.05).The expression level of AQP5 protein was significantly decreased,the difference was statistically significant(P<0.01),but the level in these groups were still higher than normal group,and the AQP5 protein was mainly expressed in the acinus membrane.Conclusion:The effect of Banxia Qinlian Decoction may be to improve exocrine inflammatory lesions by regulating AMPK or other pathways.The release of IL-17 and it’s downstream inflammatory cytokines was inhibited by activating the PPARy pathway.This effect can improve the microenvironment formed by inflammatory factors and improve the anomalous distribution of AQP5 protein.In this way,the AQP5 protein can reduce the distribution on the basement membrane and increase on the acinus membrane,thereby improving the function of exocrine water transfer and finally improving the SS symptoms.2 Clinical researchObjective:To observe the clinical effects and safety of Banxia Qinlian(BXQL)decoction on sjogren syndrome.Methods:We completed 35 patients with SS from March 2016 to February 2018 in the rheumatology.On the basis of routine treatment,all patients were treated with BXQL decoction for 3 months,and were followed up at 0 month(entering the group)and 1,2 and 3 months.Statistical laboratory inspection indicators were test before and after treatment.,and evaluating clinical efficacy and safety.(1)the primary outcomes:dry mouth VAS score,dry eyes VAS score.and the score of signs and syndrome;(2)secondary outcomes:1 TCM symptom score;2 inflammatory index:ESR,CRP;3 immune index:IgG,IgM,IgA.Safety indicators:adverse reactions in blood routine,liver and kidney function,electrocardiogram,and experimental process.Results:(1)Baseline data of 35 SS patients:3 males and 32 females,mean age 53.9±8.87 years,mean disease duration 7.86±4.29 years,26 patients with pSS,9 patients with sSS,3 patients secondary to SLE,followed 6 cases occurred in RA.(2)Main evaluation indicators:VAS of dry mouth and comparison of dry eye VAS scores:Compared with before treatment,dry mouth VAS and dry eye VAS scores showed a downward trend at the 4th week(P>0.05).At the 8th and 12th week of treatment,VAS of dry mouth and dry eye decreased significantly(P<0.01).The VAS of dry mouth and VAS scores of dry eyes were compared:The effective rate of VAS score was 77.14%for dry mouth and 85.72%for dry eye.The scores of TCM syndromes in patients with SS were significantly decreased(P<0.01).The total effective rate of SS of Chinese Herbs Banxia Qilian Decoction was 82.68%.(3)Secondary evaluation index:1,Compared with pre-treatment,weakness,shortness of breath,coughing up phlegm,fullness in the epigastrium,belching,epigastric upset and sour regurgitation,soreness of waist and backache,feverishness in palms and soles,arthralgia and dry stool scores decreased significantly,the difference was statistically significant(P<0,05,P<0.01).nasal cavity dryness,dry skin,cough,tinnitus,rash and tongue coating showed a downward trend(P>0.05).2,Compared with pre-treatment,the ESR of SS patients decreased significantly after treatment(P<0.05);the CRP showed a decrease trend,but the difference was not statistically significant(P>0.05).3,Compared with pre-treatment,the expression level of IgG protein decreased significantly after treatment(P<0.05);the expression level of IgM and IgA showed a decrease trend,but the difference was not statistically significant(P>0.05).4,There were no obvious abnormalities be observed in the safety indexes during the study,and no untoward effect were heppened during the treatment.Conclusion:Banxia Qinlian Decoction can significantly improve patients’ clinical symptoms and improve the levels of ESR and IgG,indicating that Banxia Qinlian Decoction is effective in the treatment of SS and can protect the patients’ exocrine glands better. |
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