左归丸和右归丸对实验性自身免疫性脑脊髓炎大鼠轴突再生过程中脑源性神经营养因子表达及环磷酸腺苷/蛋白激酶A信号转导通路的作用

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