, Volume 20, Issue 1, pp 24-30

Effects of Zuogui Pill (左归丸) and Yougui Pill (右归丸) on the expression of brain-derived neurotrophic factor and cyclic adenosine monophosphate/protein kinase a signaling transduction pathways of axonal regeneration in model rats with experimental autoimmune encephalomyelitis

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Abstract

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 post-immunization (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 mechanism of ZGP may be different from those of YGP.

Supported by the National Natural Science Foundation of China (No. 30873230), Beijing Natural Science Foundation (No. 7092014), Scientific Research Common Program of Beijing Municipal Education Commission (No. KM2007100025015), and Funding Project for Academic Human Resources Development in Institutions of Higher Learning Under the Jurisdiction of Beijing Municipality (No. PHR201008401)