Heavy Muscle Tablets Anti Myasthenia Gravis Mechanism

Myasthenia gravis (MG) is a T cell-regulated , antibody-mediatedautoimmune disease. Impaired neuromuscular transmission characteristic ofMG results from antibodies against the nicotinic acetylcholine receptor(AchR) of skeletal muscle.Experimental autoimmune myasthenia gravis (EAMG)is a well-established animal model for human myasthenia gravis (MG),whichis induced in susceptible strains of animal by s.c. immunizations with anemulsion of AchR and CFA.The Th1 cytokines IFN-γ and IL-2 and TNF-α,aswell as the Th2 cytokines IL-4,IL-6,IL-10, might be involved in thedeveloped of both MG and EAMG, while TGF- β and IFN- α may have asuppressive effect in both diseases. Zhong Jiling is an effective herbal prescription to treat Myastheniagravis (MG) mainly consisting in Radix Astragali Seu Hedysari, RadixGinseng and Hairy Antler etc. Zhong Jiling has been used to treat more thanthousands MG cases and got good result.This thesis, which establishing EAMGmodel in rats and focusing on cytokines IFN-γ,IL-4, TGF-βetc, studiedthe functional mechanism of Zhong Jiling preventing from MG. The main contents are below:1 Effect of Zhongjiling Tablet on experimental autoimmune myastheniagravis (EAMG) rat To investigate the influence of Zhongjiling tablet to experimentalautoimmune myasthenia gravis (EAMG). Lewis rats were immunized with N2-AchR(from Torpedo's electrical organ) in CFA. EAMG rats on day 25 after thefirst immunization were treated by Zhongjiling Tablet .The rats'weights,symptoms, activities electromyograms,anti-N2-AchRab titers, the numbersof AchR in muscles and lymphocyte proliferation were observed . we foundthat EAMG rats of Zhongjiling Tablet groups: the weights ,activities andthe numbers of AchR in muscle increased, anti-N2-AchRab titers decreased,symptoms and electromyograms were improved, the numbers of lymphocytestimulated by ConA were increased and those by AchR were reduced(P<0.01or P<0.05). Zhongjiling Tablet inhibits lymphocyte proliferation excitedby AchR and up-regulates those stimulated by ConA, which shows ZhongjilingTablet treat EAMG by immunoloregulation.2 Effect on immune function of Zhong Jiling to normal and immunosuppressivemice4 重肌灵片抗重症肌无力作用机理研究 Zhong jiling enhances lymphocyte proliferation responses to Con A andIL-2 secreting of normal mice, as well as immunosuppressive mice. Thisprove that Zhong jiling takes on character of immunoregulation.3 Effect of Zhongjiling Tablet on IFN- γ , IL-4 , TGF- β and mRNA inexperimental autoimmune myasthenia gravis (EAMG) ratTo explore the molecular mechanism of Zhongjiling Tablet therapy to EAMG.Lewis rats were immunized with puried N2-AchR (from Torpedo's electricalorgan) in CFA. ELISA and RT-PCR were adopted to determine IFN-γ,IL-4,TGF-β levels and mRNA expression. IFN-γ,IL-4 mRNA and levels in modelgroup were higher than CFA group(P<0.01 ); . IFN-γmRNA and level inmodel group was dramatically higher than Zhongjiling Tablet groups(P< 0.01 ) . IL-4 mRNA and levels in Zhongjiling Tablet groups weresignificantly lower than model group(P<0.05). TGF-βmRNA and levels inZhongjiling Tablet groups were higher than model group (P<0.01 or P<0.05). In conclusions IFN-γplays a dominant role in the developmentof EAMG. Zhongjiling Tablet inhibits over-secreting of IFN-γand IL-4 byincreasing TGF-β level. In result, anti-N2-AchR total IgG, IgG1, IgG2titers in serum of EAMG rats were reduced.To explore the effect of Zhongjiling Tablet on NO and NOS in EAMG. Lewisrats were immunized with puried N2-AchR (from Torpedo's electrical organ)in CFA. NO and NOS levels in model group were higher than CFA group(P<0.01 ); NO and NOS levels in Zhongjiling Tablet group was dramaticallylower than model group(P<0.01). Zhongjiling Tablet inhibits NO and NOSlevels to treat EAMG. In another side, Zhong Jiling has a obvious functionof inducing activated T-cell apoptosis of EAMG .