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Clinical Observation Of Mongolian Medicine Zhonglun A Decoction In The Active Period Of RA And Its Effect On Immunoregulation Mechanism Of CIA Model Rats

Posted on:2016-05-04Degree:DoctorType:Dissertation
Country:ChinaCandidate:R M D L NaFull Text:PDF
GTID:1104330461493149Subject:Chinese medical science
Abstract/Summary:
Part 1 Literature ReviewReview 1 Research progress of Mongolian medicine on RAReview 2 Research progress of Mongolian medicine Zhong Lun AtangReview 3 Research progress of Cell factor in RAPart 2 Clinical ResearchTopic:Mongolian medicine Zhong Lun Atang on active period RA clinical efficacy and safety evaluationObjective:The research of Mongolian medicine Zhong Lun Atang in treating active rheumatoid arthritis clinical efficacy and safety.Methods:90 patients with active RA were randomly divided into treatment group control group,45 patients in each group.The treatment group was given Methotrete tablets 10mg/w +Zhong Lun Atang 2/d,5g/times, shuijianbi;The control group was given Methotrexate tablets 10mg/w,two groups were treated for 12 weeks. Observe and record, two groups of patients before and after treatment the changes of clinical indices.Timely observation,patients with possible adverse reactions, signs.The data were statistically analyzed, to evaluate the clinical efficacy and safety of two groups.Results:l.The completion of the situation:The study included 90 patients with active rheumatoid arthritis patients,among them a total of 87 patients completed the trial,fall off in 3 cases (treatment group 1 cases, control group 2 cases),no elimination patients,the fall off rate is 3.33%.The two groups in sex, age, course of disease, clinical index before treatment, there was no significant difference (P>0.05), comparable.2.The clinical symptoms, physical signs:Two groups of patients after treatment time of morning stiffness,number of joint pain, joint tenderness count, swollen jointcount,average grip strength of hands,15m walking time,patient selfassessmentVAS, doctor evaluation VAS, joint function index etc clinical symptoms, signs were obviously improved than before treatment, the difference was statistically significant (P<0.05); The treatment group after treatment, improve the clinical symptoms, signs and significantly better than the control group, the difference was statistically significant (P< 0.05).3.In the Mongolian medicine syndrome symptoms, physical signs:Two groups of patients after treatment redness, fever, joint joint joint swelling, joint burning or tingling, encounter heat intensified,fever, chills, malaise, fatigue, loss of appetite, etc Mongolian medicine syndrome symptoms were obviously improved than before treatment, the difference was statistically significant (P<0.05); The treatment group after treatment, Improve the Mongolian medicine syndrome ymptoms significantly better than the control group,the difference was statistically significant (P< 0.05).4.In the laboratory indexes:Two groups of patients after treatment RF, CRP, ESR etc laboratory indexes than before treatment significantly improved, with significant difference (P<0.05); The treatment group after treatment RF, CRP, ESR etc laboratory indicators improved significantly better than the control group, the difference was significant (P<0.05). The treatment group after treatment anti CCP antibody significantly improved than before treatment, with significant difference (P<0.05); The control group after treatment anti CCP antibody than before treatment had no obvious improvement, no significant difference (P>0.05); The two groups after treatment comparison of anti CCP antibody, no significant difference (P>0.05).5.In terms of the evaluation of the health status of the patients:Two groups of patients after treatment the HAQ disability index, HAQ discomfort index, HAQ total etc were significantly improved compared with before treatment,with significant difference (P<0.05);The treatment group after treatment the HAQ disability index, HAQ discomfort index, HAQ total the improvement was significantly better than the control group, with significant difference (P<0.05).6.Mongolian medicine syndrome comprehensive curative effect:The total effective rate of treatment group is 100%(reveals rate 22.73%), control group the total effective rate was 76.74%(reveals rate 0%), after statistical analysis, the total efficiency of two groups and reveals rate there was significant difference (P< 0.05).7.The DAS28 score:Comparison of two groups of patients before treatment, DAS28 score, there was no significant difference (P>0.05); The two groups after treatment in patients with DAS28 scores were significantly improved than before treatment, with significant difference (P<0.05); After treatment, DAS28 score of the treatment group was better than control group, with significant difference (P< 0.05).8.The ACR effect evaluation:44 cases of ACR20 improvement in treatment group after treatment, for 100% of the total numbers; 21 cases of ACR20 improvement in control group, for 48.84% of the total numbers; After statistical analysis two groups of ACR20 improvement rate, with significant difference (P<0.05); 35 cases of ACR50 improvement in treatment group after treatment, for 79.55% of the total numbers; 0 cases of ACR50 improvement in control group, for 0.00% of the total numbers; After statistical analysis two groups of ACR50 improvement rate, with significant difference(P<0.05); 0 cases of ACR70 improvement in two groups after treatment, failure to do statistical analysis.9.The safety evaluation:The treatment group there were 4 cases of gastrointestinal adverse reactions in patients with, control group had 3 cases of gastrointestinal adverse reaction,3 cases of patients with skin rash, symptomatic treatment after the symptoms have been alleviated.Two groups of patients before and after treatment, blood, urine, stool routine, electrocardiogram and liver, renal function was in normal range.Conclusion:Mongolian medicine Zhong Lun Atang has certain curative effect on the active stage of rheumatoid arthritis, safe, reliable, can and antirheumatic (Methotrexate Tablets) combined with the use of, have a good synergistic effect. the total numbers; 0 cases of ACR50 improvement in control group, for 0.00% of the total numbers; After statistical analysis two groups of ACR50 improvement rate, with significant difference(P<0.05); 0 cases of ACR70 improvement in two groups after treatment, failure to do statistical analysis.part 3 ExperimentalTopic:Effects of Mongolian medicine Zhong Lun Atang on immune regulation mechanism of CIA model ratsObjective:To investigate the effect of Mongolian medicine Zhong Lun A Tang on immune regulation mechanism of CIA model rats.Method:This study first use of bovine collagen type Ⅱ Establishment of SD rat CIA model, the rats were randomly divided into normal group, the CIA model group, Mongolian medicine high, middle, low dose group and much glucoside of thunder god cane positive control group. Were observed the general condition of the rats, measurements at different time points body weight, a rear foot thickness and arthritis index; After treatment the thymus index of rats was detected, the spleen index and peyer’s patch; HE staining and immunohistochemical staining of ankle joint tissue of rats, histopathological changes of joints were observed under the light microscope and the expression of IFN-γ、TGF-β in joints; Detection of ELISA method in serum of rats IFN-γ、TGF-β、anti CⅡ antibody content; Expression of western blot method in rat joint detection IFN-γ protein.Results:1.Observe the general situation:The normal group rats were generally in good condition; CIA rats diet, stool, activities reduce the volume, sleepiness, hair ruffled, matt, hair removal etc; After administration, except for the model group, rats in each treatment group generally situation getting better, among them the Tripterygium wilfordii group and Mongolian medicine high dose group was significantly better than the other treatment groups.2.The change of body weight:The normal weight group rats increased gradually, and valueadded fastest,compared with CIA group, there was significant difference (P<0.01). After administration, in addition to the model group outside of each treatment group were all improved body weight growth, among them tripterygium wilfordii group and Mongolian medicine high dose group improved the most obvious, is a significant difference compared with model group and Mongolian medicine low dose group (P<0.01).3.Rear foot thickness change:After immunization started around lOd, a rear foot thickness increased significantly, compared with the normal group, there was significant difference (P<0.01). Among which the model group is most obvious, after immunization of 20-25d peaked, after slight easing, but in the 40d, at the end of treatment to heal the situation still is not optimistic. Rats in each treatment group a rear foot thickness with time have different degrees of improvement, among them tripterygium wilfordii group and Mongolian medicine high dose group improved the most obvious, is a significant difference compared with model group and Mongolian medicine low dose group (P<0.01).4.Arthritis index (AI) changes:After immunization started around 5d,CIA rats were significantly increased AI value, compared with the normal group, there was significant difference (P<0.01). The model group has been at a high level, after slight easing, but in the 40d, at the end of treatment to heal the situation still is not optimistic. Rats in each treatment group AI values decreased with time, from the 20d start after vaccination compared with the model group, there was significant difference (P<0.05), among them the decline of Tripterygium wilfordii group and Mongolian medicine high dose group was most obvious, is a significant difference compared with the Mongolian medicine low dose group (P<0.05).5.The thymus index, spleen index and peyer’s patch counting change:Rats model group thymus index, spleen index and peyer’s patch counting was significantly increased than normal group (P<0.01), the thymus index, spleen index and peyer’s patch counting the rats in the model group compared with the normal group, there was significant difference (P<0.01), each treatment group could reduce the CIA rats thymus index, spleen index and peyer’s patch counting, among them the decline of Tripterygium wilfordii group and Mongolian medicine high dose group was most obvious, is a significant difference compared with model group and Mongolian medicine low dose group (P<0.05).6.The histological change of articular tissue pathology:The model group rats ankle HE slice, synovial hyperplasia, cell infiltration and bone destruction of integral were significantly increased, compared with the normal group, there was significant difference (P<0.01):Rats in each treatment group ankle joint synovial proliferation, cell infiltration and bone destruction integral integral have different degrees of improvement, among them the decline of Tripterygium wilfordii group and Mongolian medicine high dose group was most obvious, is a significant difference compared with the model group (P<0.05).7.Serum IFN-γ、TGF-β、anti CⅡ antibody content change:In serum of model group IFN-y anti CⅡ antibody level was significantly higher,compared with the normal group, there was significant difference (P<0.01); Rats in each treatment group serum IFN-γ、anti CⅡ antibody levels were decreased to different extent, is a significant difference compared with the model group (P<0.01), among them the decline of Tripterygium wilfordii group and Mongolian medicine high dose group was most obvious, is a significant difference compared with model group and Mongolian medicine low dose group (P<0.01). In serum of model group TGF-β decreased level, compared with the normal group, there was significant difference (P<0.01); Rats in each treatment group serum TGF-P levels were increase to different extent, is a significant difference compared with the model group (P<0.01), among them the increase of Tripterygium wilfordii group and Mongolian medicine high dose group was most obvious, is a significant difference compared with model group and Mongolian medicine low dose group (P<0 .01).8.Ankle joint IFN-γ、TGF-β changes of positive expression:Ankle joint of model group IFN-y positive expression obvious rise,compared with the normal group, there was significant difference (P<0.01); Rats in each treatment group ankle joint IFN-y levels were decreased to different extent, is a significant difference compared with the model group (P<0.01), among them the decline of Tripterygium wilfordii group and Mongolian medicine high dose group was most obvious, is a significant difference compared with model group and Mongolian medicine low dose group (P<0.05).Ankle joint of model group TGF-β positive expression Decreased obviously, compared with the normal group, there was significant difference (P<0.01); Rats in each treatment group ankle joint TGF-β levels were increase to different extent, is a significant difference compared with the model group (P<0.01), among them the increase of Tripterygium wilfordii group and Mongolian medicine high dose group was most obvious, among them the decline of Tripterygium wilfordii group and Mongolian medicine high dose group was most obvious, is a significant difference compared with model group and Mongolian medicine low dose group (P<0.01).9.Joint IFN-y protein expression changes:Joint of model group IFN-γ protein expression obvious rise,compared with the normal group, there was significant difference (P<0.01); Rats in each treatment group joint IFN-γprotein expression levels were decreased to different extent, among them the decline of Tripterygium wilfordii group and Mongolian medicine high dose group was most obvious, is a significant difference compared with model group and Mongolian medicine low dose group (P<0.01).Conclusion:Mongolian medicine Zhong Lun Atang improve the general condition of the rats arthritis, body weight, rear foot thickness, arthritis index, thymus index, spleen index, peyer’s patch counting change and histological change of articular tissue pathology; Can improve rat serum IFN-γ、TGF-β、anti CⅡ antibody content changes and ankle joint IFN-γ、TGF-β changes of positive expression; Can improve rat joint IFN-y protein expression changes; Its curative effect is close to the positive control medicine Tripterygium glycosides, But there is dose effect relation, Mongolian medicine Zhong Lun Atang high dose curative effect than middle dose and low dose.
Keywords/Search Tags:Mongolian medicine Zhong Lun Atang, Active stage of rheumatoid arthritis, Curative effect, safety, CIA model, Immune regulation mechanism
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