Objective：To study the molecular mechanism of Zuogui Pill（左归丸,ZGP） and Yougui Pill（右归丸,YGP） on axonal regeneration in rats with experimental autoimmune encephalomyelitis（EAE）.Methods： EAE rat model was established by bilateral rear pedes subcutaneous injection of antigen made by mixing myelin basic protein（MBP） and complete Freud＇s adjuvant（CFA） in the volume ratio of 1：1.The pathological changes of axonal injury and regeneration in the brain and the spinal cord were observed on the 14th（the acute stage） and the 28th day（the remission stage） after modeling,with hematoxylin-eosin（HE） staining,silver stain, and immunohistochemical staining.The rats treated with prednisone acetate were taken as controls.Results： Observation under the light microscope with HE staining showed a sleeve-like change in rats＇ cerebrospinal parenchyma with inflammatory cell infiltration around the small vessels and neuronic denaturation,while silver staining showed excessive tumefaction and abscission of axon,and immunohistochemical analysis showed decreasing of nerve growth factor（NGF） expression at the acute stage of EAE,which was even more remarkable at the remission stage,showing significant difference as compared with the normal control（P〈0.05）. And the expressions of Nogo A,an axon growth inhibitor,and its receptor（Nogo-66 receptor,Ng R） were significantly higher than those in the normal control at the acute stage（P〈0.01）.However,after the intervention of ZGP and YGP,the pathological changes and axon damage in rats＇ brain and spinal cord were much more alleviated,and the NGF expression was significantly higher than that in the model group at the acute stage （P〈0.05）.The expression of NGF was even stronger during the remission stage,and a better effect was shown by YGP.As for Nogo A and Ng R expressions,they were significantly lower than those in the model group at the acute stage（P〈0.05）,but a better effect was shown by ZGP.Conclusions：ZGP and
Objective：To study the effects of Zuogui Pill（左归丸,ZGP）and Yougui Pill（右归丸,YGP）on the expressions of brain-derived neurotrophic factor（BDNF）and cyclic adenosine monophosphate（cAMP）/protein kinase A（PKA）signaling of axonal regeneration in the Lewis rats with experimental autoimmune encephalomyelitis（EAE）,in order to explore the possible mechanism of ZGP and YGP on promoting axonal regeneration.Methods：The rats were randomly divided into normal control（NC）,model（MO）,prednisone acetate（PA）,ZGP and YGP groups.The EAE model of rat was established by injecting antigen containing myelin basic protein（MBP）68-86.The brain and spinal cord were harvested on the 14th and 28th day postimmunization（PI）,the protein and mRNA expression of BDNF and PKA in the brain and spinal cord of rats were detected by Western blot analysis and real-time quantitative polymerase chain reaction（PCR）,and the cAMP levels were detected by using enzyme-immunoassay method.Results：（1）On the 28th day PI,the mRNA expression of BDNF in brain white matter and spinal cord of rats in ZGP and YGP groups were up-regulated,especially in YGP group（P〈0.05 or P〈0.01）.（2）On the 14th day PI,the cAMP levels in brain white matters significantly increased in PA and YGP groups compared with MO group（P〈0.05 or P〈0.01）,and the cAMP level in YGP group was higher than that in ZGP group（P〈0.05）.The cAMP level in spinal cord also significantly increased in YGP group compared with MO,PA and ZGP groups,respectively（P〈0.01）.（3）On the 14th day PI,the PKA expression in spinal cord of rats in ZGP group was significantly decreased compared with MO and YGP groups,respectively（P〈0.05）.（4）On the 28th day PI,there was a positive correlation between cAMP and PKA expression in the brain white matter of YGP rats.Conclusions：The results suggest that ZGP and YGP may promote axonal regeneration by modulating cAMP/PKA signal transduction pathway,but the targets of molecular mec
