| The paper is divided into three parts,the first part is the clinical trial;the second part is the animal experiment;the third part is the literature review;the clinical trial part observes the reliability and effectiveness of acupuncture for ankylosing spondylitis(AS)and the relevant mechanism of acupuncture for AS.From the perspective of AS and IL-23/Th17(interleukin-23/helper cells),the scientific connotation of the mechanism of acupuncture on AS,and this paper discusses the aspects of the cause,pathogenesis,ankylosing spondylitis(AS),western medicine,and the role of IL-23/Th 17 inflammation axis in AS.research backgroundIn recent years,with the progress of society and the development of The Times,the incidence of ankylosing spondylitis(ankylosing spondylitis,AS)patients is getting higher and higher in the population,and it is getting younger and younger.Epidemiological studies show that the peak of AS onset is 15 to 35 years old,and the average age of onset is about 25 years old.It is rare in the age group of less than 8 years old and greater than 40 years old,and it is more common in men.Ankylosing spondylitis is a chronic and progressive inflammatory autoimmune disease,which is universally recognized as difficult to cure.It is generally believed that the disease is caused by the interaction of genetic,infectious,environmental,autoimmune and endocrine factors.The lesions mainly involve the invasion of the axial joint,with sacroiliac arthritis,apitis and new bone formation as the main pathological changes,which lead to joint deformity and rigidity in severe cases.Therefore,generally patients with AS are accompanied by limited spinal activity and movement.For the treatment of AS,there is still a lack of radical cure.The purpose of the treatment is mainly to relieve the back and joint pain,reduce inflammation,delay the evolution and development of the disease,improve the spinal activities and limb movement function,improve the quality of life,and prevent the complications of spinal diseases.Moreover,the pathogenesis of AS is still not clear,so the pathogenesis and treatment of ankylosing spondylitis urgently need new research and exploration.A lot of previous studies have shown that the IL-23/Th17 inflammatory axis and related inflammatory cytokines(including IL-23,IL-17,TNF-α,CRP,ESR,etc.)play an important role in the development of AS,Become a new target for treating AS,In addition,the tutor group achieved satisfactory results through acupuncture in the early stage,Can significantly improve the joint range of motion in patients with AS,Relieve symptoms such as low back and joint pain,However,the mechanism of acupuncture for AS has not been defined,And no rigorous animal experiments and randomized controlled clinical(RCT)trials,Based on the above facts,This study is intended to adopt a rigorous randomized controlled clinical trial(RCT)and animal experiments,systematically observe the clinical efficacy of acupuncture in patients with AS,and to explain its mechanism of action.This experiment was obtained from the National Nature Foundation of China project "Study on the mechanism of ankylosing spondylitis based on IL-23/Th17immune-inflammatory axis"(81960897)purpose of researchThe clinical efficacy of acupuncture in AS patients was systematically evaluated by a rigorous RCT test.The bovine cartilage-derived proteoglycan-induced AS animal model(PGIA mouse model)was used to investigate the regulatory effect of acupuncture on IL-23/Th17 inflammatory axis-related indicators(TNF-α,IL-17,and IL-23,etc.),so as to provide a theoretical basis for the effectiveness of clinical acupuncture in treating AS.research techniques1.Clinical study: 70 cases of ankylosing spondylitis patients from the second and third Affiliated hospitals of Yunnan University of Traditional Chinese Medicine were randomly divided into acupuncture group and control group by randomized control and 36 cases of acupuncture group and 34 cases of control group.The control group and acupuncture group were all conducted on the basic treatment of combined medication.The control group received oral sulfasalazine enteric-coated tablets and celecoxib capsules combined with common acupuncture treatment.Celecoxib capsules: 1 tablet/time,2times/day;sulfasalazine enteric-coated tablets: 1 week,1 tablet/time,3 times/day;2 week,2 tablets/3 times/day;3 week,4 tablets/3 times/day;continue to maintain the current dose for 1 month;acupuncture(mainly spinal)once/day,7 consecutive treatment for one course,3 days,3 courses of treatment,namely 1 month.The acupuncture group gave empirical acupuncture treatment on the basis of combined medication(mainly the meridian,bladder meridian,kidney meridian),selected a group of acupoints every day,alternating use,once a day,7 consecutive treatment for a course,each course of rest for 3 days,a total of 3 courses of treatment,that is,1 month.Ankylosing spondylitis measuring index(BASMI)and Keitel function test scale for AS patients before and after treatment,and at the same time for peripheral blood inflammatory factors,using C response protein(CRP)and blood sink(ESR)expression level,finally to the above scale and peripheral blood inflammatory factors were statistically treated.2.Animal experiments: Bovine cartilage-derived protein glycans were used by intraperitoneal injection of mouse induced arthritis model(PGIA)as an animal model of ankylosing spondylitis.Thirty-two BALB/c mice were randomly assigned to blank control(N),model(M),acupuncture(Z),and celecoxib(S)in each group,and 24 were PGIA except for the normal group.The equal amounts of core proteoglycan were injected intraperitoneally on days 0,20,and 40,along with an equal dose of 0.9% saline.After mold making,during days 41-70,the intervention was performed as required by the experimental design [acupuncture treatment 3 times per week,1 other day,a total of 12times].After the experiment,the mice were treated and all the experimental indicators were observed.The main experimental observations include:(1)International Animal Joint Score Scale;(2)collected serum,enzyme-linked immunosorbent test(IL-23 to measure the expression levels of TNF-α and IL-17;(3)performed histopathological observation of the sacroiliac joint and claw joints by HE staining.findings1.clinical research(1)Baseline: A total of 70 cases were included,9 cases were lost,and 1 case was eliminated.The shedding rate was 12.85%,the elimination rate was 1.42%,and 60 effective cases were completed(30 cases each in the observation group and 30 cases in the control group).There was no significant difference in gender,age,scale score(BASMI,Keitel function test)and inflammatory index(CRP,ESR)between the two AS groups before statistical analysis,and there was no significant difference(P>0.05),and the baseline was comparable.(2)Scale score: After treatment,the BASMI and Keitel function scores were significantly lower than before treatment,and the difference was highly significant(P=0.000<0.01);after treatment,the acupuncture group decreased significantly in BASMI and Keitel function scores compared with the control group,and the difference was highly significant(P=0.002<0.01).Moreover,it was found that the BASMI scores of the two groups fluctuated significantly with the trend of time points(P=0.000<0.01),and the two groups had a significant effect on time interaction,and the difference was highly statistically significant(P=0.000<0.01),while the acupuncture group showed a more significant fluctuation in the BASMI score and Keitel functional test score than the control group.The rating scale proved that both groups could effectively improve AS limb motion and spinal mobility,while the acupuncture group was better than the control group in improving limb motion function and spinal activity,proving that acupuncture could effectively improve limb joint motion function and spinal mobility in AS patients,prevent joint stiffness and deformation,and reduce the disability rate.(3)Expression of inflammatory factors levels in peripheral blood: after treatment,CRP and peripheral expression,ESR in peripheral group compared with those before treatment,However,the decreasing trend in the control group of CRP was not significant,No statistically significant data(P=0.069>0.05),However,the ESR expression level was significantly reduced compared with that before treatment,The difference was highly statistically significant(P=0.000<0.01);However,in the observation group,the expression of CRP and ESR levels was significantly reduced compared with that before treatment,The difference was highly statistically significant(P=0.000<0.01);post-treatment,Comparing the observed group with the control group,The observation group decreased the ESR expression level in AS patients compared with the control group,The difference was statistically significant(P=0.011<0.05),In terms of the suppression of the CRP expression levels,Trend of decrease was more significant in the observed group,The difference was extremely highly statistically significant(P=0.000<0.01).In addition,it was found that the peripheral ERP and ESR expression levels fluctuated significantly with the time point(P=0.000<0.01),and the observation and control group had a very significant effect on time interaction,and the difference was highly statistically significant(P=0.000<0.01).This shows that both groups could inhibit the expression levels of CRP and ESR in peripheral blood,while the observation group was better than the control group in inhibiting inflammatory cytokines,further proving that acupuncture could effectively inhibit the expression level of inflammatory cytokines,and the mechanism of action may be related to the anti-inflammatory effect of acupuncture.2.Animal experiments(1)Arthritis score: relative to the blank control group,after immunization of BALB/c mice with bovine cartilage-derived protein glycan,each group spontaneously developed swelling of paw joints,and the arthritis score increased significantly(P<0.01),indicating successful mold making.After treatment,compared with the model group,the acupuncture group decreased,and the difference was statistically significant(P=0.047<0.05),while between the celecoxib group and the model group,the difference was not statistically significant(P>0.05),indicating that the acupuncture had a better effect on the inflammation of PGIA mice,while the acupuncture group showed a downward trend compared with the celecoxib group,but the difference was not statistically significant(P>0.05).(2)Serum IL-17 and serum IL-23:relative to the blank control group,the serum expression of IL-23 and IL-17 in the other groups,with a highly statistically significant difference(P=0.000<0.01),indicating that the expression of serum IL-23 and IL-17 in mice,which proved the imbalance of IL-23/Th-17 inflammatory axis in the PGIA mouse model.After treatment,the serum expression trend of IL-23 and IL-17 were significantly decreased in the acupuncture and celecoxib group compared with the model group,and the difference was highly statistically significant(P<0.01).post-treatment,There was no significant difference in serum IL-23 levels in the acupuncture group as compared with IL-23 in the celecoxib group,not statistically significant difference(P>0.05),It shows that there is no obvious difference between acupuncture and celecoxib in inhibiting serum IL-23 expression;The serum IL-17 expression of IL-17 in IL-17 in the celecoxib group,The difference was very highly significant(P<0.01),Shstrated that acupuncture caused more significant serum IL-17 inhibition in PGIA mice than celecoxib drugs,Acupuncture can effectively modulates the IL-23/Th-17 inflammatory axis,Inhibition of inflammatory factors,which in turn inhibited and decreased the inflammatory response.(3)Serum TNF-α: after molding,With the blank control group,High serum expression level of TNF-α in PGIA mice(P=0.000<0.01),This indicates that there is an inflammatory factor imbalance in PGIA mice;After the treatment,Compared to the model group,The TNF-α expression levels were decreased in both the acupuncture and celecoxib groups,Among them,the trend of TNF-α expression level in the celecoxib group,The difference was statistically significant(P<0.05),TNF-α expression level in the serum of the acupuncture group,The difference was extremely highly statistically significant(P=0.000<0.01).It shows that acupuncture can inhibit the expression of TNF-α level and reduce inflammatory factors.The difference was significant from acupuncture group to celecoxib group(P<0.01),indicating that acupuncture reduced TNF-α levels compared with celecoxib group.(4)HE staining of the sacroiliac and hind paw joints: After HE staining,the space of the sacroiliac joint was narrowed,a large number of inflammatory cells infiltrated in the sacroiliac and surrounding tissues,the cartilage distribution of the sacroiliac joints was uneven and inflammatory cells infiltrated to different degrees in the hind paw,indicating the success of the PGIA mouse model.After treatment,the involvement of the sacroiliac joint and the hind paw was improved compared with the model group,the sacroiliac joint space was slightly improved,the distribution of cartilage at the sacroiliac joint edge was more regular than that of the model group,and the inflammatory cell infiltration in the sacroiliac and hind paws was reduced,but there was still some inflammatory cell infiltration.According to the HE staining images,the invasion degree of sacroiliac and hinpenitis cells was significantly less than that of the celecoxib group,indicating that the acupuncture group was better than the celecoxib group in the improvement of sacroiliac and hind paw arthritis.conclusions1.Acupuncture can effectively improve AS patients limb joint movement function and spinal motion(such as waist bending,waist bending,neck rotation degree,squatting,standing,and chest breathing function mobility,etc.),prevent,delay joint stiffness deformation,reduce disability rate,its mechanism may be associated with acupuncture has anti-inflammatory,regulate the level of inflammatory factors.2.The results of this study showed that the BALB/c mouse induced AS model(PGIA mouse model)was successfully constructed,and there was an imbalance of the IL-23/Th17 inflammatory axis in PGIA mice.Acupuncture can play an anti-inflammatory and immune role by regulating the expression level of TNF-α,IL-17 and IL-23 inflammatory factors in the IL-23/Th 17 axis,improving the infiltration of inflammatory lymphocytes in the hindpaw joint and repairing the destruction of the bone of the joint surface,which may be one of the mechanisms of acupuncture for AS. |
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