Study Of "Bushen Qiangdu Therapy" On Anky Losing Spondylitis And Superficial Research Of The Anti-ossification Effect

Objective:1. To evaluate the clinical efficacy and safety of "Bushen Qiangdu Therapy" in the treatment of ankylosing spondylitis (AS) by a systematic review and meta analysis.2. To evaluate the clinical effect and reveal the anti-ossification effect of "Bushen Qiangdu-Integrated Therapy" on joint function and imaging progression of AS through a prospective, randomized and controlled study.3. To explore the anti-ossification effect of "Bushen Qiangdu Therapy" through vitro study of exploring the influence of Bushen Qiangdu Decoction on fibroblast cells proliferation and osteogenic differentiation based on connexin43.Methods:1. Literature review:Analysed the randomized controlled trials (1985/2015-5) that used "Bushen Qiangdu Therapy" in the treatment of AS. Used the key words searching PubMed (1985/2015-5). Embase (1985/2015-5)、ScienceDirect (1985/2015-5)、 CBM (1985/2015-5)、VIP (1985/2015-5)、CNKI (1985/2015-5) and WANFANG (1985/2015-5) database. Managed the literature database by using Note express V3.0.2.6367. Excel was used for data extraction and Cochrane Review Manager 5.2 was used for evaluation of risk of bias and the meta analysis.2. Clinical study:AS patients with Kidney Deficiency with Governor Vessel Cold Syndrome were randomized into the CM or WM group, with 15 patients into each group for a total of 30 patients in the study. All patients received instruction in a standard AS exercise regimen. Individuals randomized into CM treatment group also received oral therapy with Bushen Qiangdu Decoction of Chinese herbs and moxibustion therapy. Patients randomized into WM treatment group also received oral therapy with celecoxib 200mg twice daily. The primary outcome is Ankylosing Spondylitis Disease Activity Score (ASDAS)-C-reactive protein (-CRP) (ASDAS-CRP) at week 48 of each arm. Secondary outcome variables are Bath Ankylosing Spondylitis Functional Index (BASFI), Bath Ankylosing Spondylitis Metrology Index (BASMI), chest expansion, ankylosing spondylitis quality of life questionnaire (ASQoL) and imaging.3. Experimental study:Fibroblasts from rat ligament cultured in vitro were used in the study. MTS was used for the detection of the effect of Bushen Qiangdu Decoction on fibroblasts proliferation. Western blot was used for the detection of the effect of Bushen Qiangdu Decoction on cbfa 1 and Cx43/pCx43 protein expression.Results:1. Literature review:923 trials were searched.214 duplicates and 673 non-randomized controlled trials were excluded. And then 23 trials not accord with standard of inclusion/exclusion criteria were excluded.13 trials with 972 subjects were included. The results showed that "Bushen Qiangdu Therapy" were more effective on improving ASAS20, ESR, VAS, TCM syndrome and Schober of AS than WM therapy (RR=1.19 [1.03,1.24],Z=2.37, P=0.02; RR= 1.17 [1.07,1.28], Z=3.44, P=0.0006; MD=-0.62 [-1.08,-0.17],Z=2.67, P=0.008; MD=-14.23 [-22.58,-5.88],Z=3.34,P0.0008; MD=0.36 [0.20,0.53], Z=4.41, P<0.0001).2. Clinical study:Significant difference within the "Bushen Qiangdu-Integrated Therapy" group and "WM-Integrated Therapy" group compared to the baseline in ASDAS-CRP, BASFI, ASQoL and SPARCC (P<0.05). No significant difference within the two groups in BASMI and chest expansion. No significant difference between the two groups (P>0.05) except the bone sclerosis, lesions and syndesmophyte, on which "Bushen Qiangdu-Integrated Therapy" showed a better effect (P<0.05).3. Experimental study:Bushen Qiangdu Decoction inhibited the proliferation of rat ligament fibroblasts on a dose based manner. Bushen Qiangdu Decoction at concentration of 500p g/ml led to the highest inhibition rate of (18.791±4.637)%(P<0.001). The protein expression of Cbfa land Cx43/pCx43 was dramatically decreased by both Bushen Qiangdu Decoction and Celecoxib (P<0.05 or P<0.001). No significant difference showed between the Bushen Qiangdu Decoction and Celecoxib group (P<0.05).Conclusion:1. Literature review:"Bushen Qiangdu Therapy" showed a better clinical efficacy compared to WM therapy, which provided proofs for the application of "Bushen Qiangdu-Integrated Therapy" in the treatment of AS.2. Clinical study"Bushen Qiangdu-Integrated Therapy" showed a good clinical effect on improving the disease activity, functional status, quality of life and bone marrow edema progression in AS, even compared to WM therapy. What’s more, "Bushen Qiangdu-Integrated Therapy" showed a better effect on improving bone sclerosis, lesions and syndesmophyte progression. It indicates that "Bushen Qiangdu-Integrated Therapy" may have the effects not only on improving joint function but also on improving abnormal ossification progression.3. Experimental study:"Bushen Qiangdu Therapy" may exert anti-AS effects via suppression of cell proliferation and osteogenic differentiation of fibroblasts by regulating Cx43. Thus, molecular mechanisms underlying anti-AS effects of traditional Chinese medical compounds can be, at least in part, elucidated.