Astragalus Compound Treatment Of Myasthenia Gravis Clinical And Experimental Research

Myasthenia gravis is a kind of autoimmune disease,it mainly involves the Acetylcholine receptor(AchR) on the postsynaptic membrane of neuromuscular junction,mediated by the specific nicotinic acetylcholine receptor(N₂AchRab), and the complement participates its process.Its characteristics involve:1.Clinical symptoms:weakness of skeletat muscle,aggravated after action,and relieved after rest,slight in daytime and gravis at night.2.Electromyography:the amplitude decreased after echo-low frequency transduction of electric stimulation,at the same time,the miniature end-plate potential decreased,and the jitter of single fiber EMG widened,even blocked.3.Pharmacology:treated with cholinesterase inhibitor is effective, and over anaphylaxis to tubocurarine.4.Immunology:the increasing of acetylcholine receptor antibody in blood serum.5,Immunopathology:the wrinkles of postsynaptic membrane at neuromuscular junction decreased,flattened,and the AchR on the postsynaptic membrane decreased,myasthenia gravis is a cosmopolitan stubborn disease,the western medical treatment has its side effect, therefore,develop the effective Chinese patent medicine is the urgent mission. the complex recipe of Astragalus membranaceus is a pure Chinese drugs pharmaceutics,developed by Pro.Zhang Jingsheng under the directions of PISHEN theory,and obtained manifest therapeutic effect on the clinical and experimental study till now.Purpose:Observe the complex recipe of Astragalus membranaceus's clinical effect in treating Myasthenia graves,provide its experimental basement;Observe the influence of the complex recipe of Astragalus membranaceus to T lymphocyte,Tc1/Tc2,Th1/Th2,IFN-γ,IL-4,TNF-α,IgG,IgA,IgM,C3,C4,AchRAb in peripheral blood of myasthenia gravis patients,reveal its immunological regulation effect on the cellulax level.Methods:1.According to the hospitalization date and the random-double blind-control principle,the myasthenia gravis patients was randomly divided into 2 groups, the curing group and the control group,30 cases per group.Patients of curing group administered the complex recipe of Astragalus membranaceus and prednisone placebo,Patients of control group administered prednisone tablet and Zhongjiling tablet placebo.Course of treatment is 90 days.Compare the pre-treatment and post-treatment clinical curative effect scores and Chinese medicals symptom scores.2.Detect the pre-treatment and post-treatment distribution of T lymphocyte subgroup of myasthenia gravis patients with flow cytometry.3.Detect the pre-treatment and post-treatment distribution of T lymphocyte subgroup Th1,Tc1,Th2,Tc2 of myasthenia gravis patients with flow cytometry.4.Detect the the pre-treatment and post-treatment level of IFN-γ,IL-4,TNF-αof myasthenia gravis patients with ELISA assay technology。5.Using the immunoturbidimetric and ELISA assay technology to detect the level of IgG,IgA,IgM,C3,C4,AChRAb in patients' peripheral blood pre-and post-administration.Results:1.Clinical research:The complex recipe of Astragalus membranaceus has significant effect to myasthenia gravis,the clinical syndrome score statistic result shows that the effective ratio of curing group is 70.0%,and that if control group is 56.7%,manifest difference exit between these two groups, P＜0.05;the change of Chinese medical symptom score statistic result shows that the effective ratio of curing group is 73.33%,and that if control group is 56.67%,manifest difference exit between these two groups,P＜0.01,it indicate that the curing group is better than that control group in improving Chinese medical symptoms.In this study,the patients in control group appeared side-effects such as sight hepatic dysfunction,increasing fasting serum glucose,femoral head necrosis and central obesity,on the contrary,The complex recipe of Astragalus membranaceus has exact curing effect without any side-effect,these shows that it is better than control group.2.Before treatment,the CD4⁺ cell percentage and CD4⁺/CD8⁺ of these two groups are higher than that of normal group,P＜0.01,the CD8⁺ and NK(CD16⁺/56⁺)cell percentage of these two groups are lower than that of normal group,P＜0.01.The CD3⁺ and B(CD19⁺) cell percentage of these two groups have no difference with that of normal group,P＞0.05.After treatment,there is no change on the CD3⁺ cell percentage of these two groups,P＞0.05,CD4⁺ and CD19⁺ cell percentage and the ratio of CD4⁺/CD8⁺ decreased significantly,CD8⁺ and NK(CD16⁺/56⁺) cell increased significantly,P＜0.05.Compare with that of control group,there is significant difference for the CD4⁺,CD8⁺,CD4⁺/CD8⁺,CD19⁺ and CD16⁺/56⁺ cell percentage,P＜0.05.3.The Th1,Th2,Tc1 and Tc2 cell percentage of these two groups are higher than that of normal group,P＜0.01,Th1/Th2 and Tc1/Tc2 have difference with that of normal group,P＜0.05.After treatment,The Th1 and Tc1 cell percentage of the curing group decreased significantly,P＜0.01,there is obvious difference with that of control group.4.The IFN-γ,IL-4 and TNF-αlevel of these two groups are significant higher than that of normal group,P＜0.01.After treatment,the IFN-γ,IL-4 and TNF-αlevel of two groups depressed,compared with that of pre-treatment, significant difference exited,P＜0.01.While in control group,the IFN-γ,IL-4 and TNF-αlevel decreased significantly,there is obvious difference with that of control group,P＜0.05.5.The AchRab level of these two groups are higher than that of normal group, P＜0.01.The IgA and IgM level of these two groups are lower than that of normal group,P＜0.01.The C₃ and C₄ level of these two groups decreased significantly, there is obvious difference with that of normal group,P＜0.05.After treatment, the C₃ and C₄ level of curing group increased,compared with that of pre-treatment,significant difference exited,P＜0.05,the AChRAb level of the curing group decreased significantly,P＜0.01,while in control group,the C₃, C₄ and AchRab level are obvious difference with that of control group,P＜0.05. Conclusion:1.The complex recipe of Astragalus membranaceus can significantly improve the myasthenia gravis pationts' clinical symptoms and Chinese medicine syndromes,Its effect of improving Chinese medicine symptoms is better than that of only using prednisone,and no adverse reaction exited in this study.2.The complex recipe of Astragalus membranaceus caused the redistribution of T lymphocyte subgroup ratio,this effect maybe due to its inhibition of Th cell proliferation,promoting Ts cell's activation and depress CD4⁺/CD8⁺ ratio, then rectified the abnormal immune response of myasthenia gravis patients, as a result,inhibited the production of auto antibody,mainly AchRab.3.Th1 and Tc1 subsets decreased in the peripheral blood after MG patients were treated with leflunomide.The effect of leflunomide might be related to the prevention of Th1 and Tc1 differentiation and the decrease of Th1 and Tc1 cytokines such as IFN-γ.4.After treatment with the complex recipe of Astragalus membranaceus,the IFN-γ, IL-4 and TNF-αlevel depressed,compared with that of pre-treatment,this indicated its immunological regulation effect.The complex recipe of Astragalus membranaceus+ prednisone has exact curing effect,it is better than that of only using prednisone.These indicate that The complex recipe of Astragalus membranaceus's immunological regulation is multi-targets and tow-way regulation.It is different with that of western medicine,which is overall inhibition to patients' immune function,and this manifest The complex recipe of Astragalus membranaceus's holo-regulation characteristic and predominance.5.After treatment,the C₃ and C₄ level of curing group increased,it suggests that defecting of the levels of the complements in MG patients has attributions to mobile MG and maybe an objective index in determing the disease severity.