【摘 要】
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Danshen has been used in stroke treatment for thousands of years in China.However, the underlying mechanism still remains elusive.Neuron loss is the cardinal feature of stroke.Stimulating endogenous n
【机 构】
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Dept of Pharmacology,School of Basic Medical Sciences,Capital Medical University,Beijing l00069,Chin
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Danshen has been used in stroke treatment for thousands of years in China.However, the underlying mechanism still remains elusive.Neuron loss is the cardinal feature of stroke.Stimulating endogenous neurogenesis, especially neuronal differentiation, might potentially provide therapeutic effects to these diseases.To interpret Danshen s diseasemodifying effects, the effects of tanshinone Ⅱ A (T Ⅱ A), the major lipophilic component of Danshen, on neuronal differentiation in rat PC12 pheochromocytoma cells and the rat embryonic cortical neural stem cells (NSCs) were observed.PC12 cells and NSCs were incubated with T ⅡA for 7 days.To detect the neuronal differentiation, GAP43 expression was detected by western blots assay and βtubulin Ⅲ expression was detected by immunocytochemical staining.Results showed that T Ⅱ A dosedependently promoted neuronal differentiation.T Ⅱ A activated mitogenactivated protein kinase 42/44 (MAPK42/44) and its downstream transcription factor, cAMP response elementbinding protein (CREB).In addition, T Ⅱ A upregulated the expressions of brain derived neurotrophic factor (BDNF) and nerve growth factor (NGF).The MEK inhibitor and the antagonist to the receptors of NGF and BDNF could partially attenuate the differentiation effects, indicating that MAPK42/44 mediated BDNF and NGF signals were involved in T Ⅱ A s differentiation effects.Caveolin1 (CAV1), the major functional protein of membrane caveolae, plays critical roles in the endocytosis of exogenous materials.CAV1, which was activated by T Ⅱ A, might help T ⅡA transport across cell membrane to initiate its differentiation effects.It was proven by the evidences that suppressing the function of caveolin inhibited the differentiation effects of T Ⅱ A.Therefore, it was concluded that T Ⅱ A promoted neuronal differentiation partially through MAPK42/44 mediated BDNF and NGF signals in a caveolaedependent manner.
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