川芎茶调散对帕金森病小鼠多巴胺神经元损伤的保护作用及机制研究

目的:研究川芎茶调散对1-甲基-4-苯基-1,2,3,6-四氢吡啶(MPTP)致小鼠多巴胺(DA)神经元损伤的保护作用,并从抗氧化角度探讨其神经保护作用的可能机制.方法:将3～5月龄的雄性C57/BL小鼠随机分为6组:正常组、川芎茶调散高、中、低(75,50,25 g·kg~(-1)生药量)3个剂量组、模型组.每组8只动物.观察爬杆实验测试行为学改变,HPLC检测小鼠纹状体中DA及其代谢产物含量,免疫组化检测小鼠黑质中TH阳性细胞数,荧光比色检测黑质中超氧化物歧化酶(SOD)活力.结果:高、中、低剂量川芎茶调散对帕金森氏病(PD)小鼠的行为损害均有一定的保护作用(P<0.01);川芎茶凋散高剂量组小鼠纹状体中DA含量及TH阳性神经元数量明显高于模型组(均P<0.05);川芎茶调散中、高剂量组相对于模型组,SOD活力显著增高(P<0.05).结论:川芎茶调散可明显改善MPTP所致的小鼠PD模型的运动障碍,同时能对MPTP引起的DA神经元损伤起到保护作用,川芎茶调散对DA神经元的保护作用可能与其较强的抗氧化能力有关.

Neuroprotective effects and mechanisms of Chuanxiong Chatiao pulvis against MPTP-induced dopaminergic neurotoxicity in mice model of parkinson's disease

Objective: To investigate the neuroprotective effects and mechanisms of Chunxiong Chatiao pulvis (CXCT) on the MPTP-induced dopaminergic neurodegneration in mice model of PD. Method: 3-5 months old male mice were randomly divided into following six treatment groups (NS+NS, 50 kg^-1 CXCT+NS, 25 kg^-1 CXCT+MPTP, 50 kg^-1 CXCT+MPTP, 75 kg^-1 CXCT+MPTP, NS+MPTP) (n=8/group). For behavioral measurement, the mice were evaluated for their motor coordination by pole-test; Striatal dopamine content of mice was measured using standard reverse-phase HPLC; Number of tyrosine hydroxylase (TH)-positive cells in the substantia nigra of mice was detected by immunohistochemistry; SOD activity in the substantia nigra of mice were measured by fluorimetry. Result: The score of pole test (25, 50, 75 kg^-1), the striatal dopamine contents (75 kg^-1), the residual DA contents (75 kg^-1) and the SOD activity in substantia nigra (50, 75 kg^-1) all showed that, the CXCT-pretreated groups significantly higher than that of the group NS +MPTP (P<0.05 or P<0.01). Conclusion: Chuanxiong Chatiao pulvis improved the motor deficit in MPTP-induced mice, and attenuate MPTP-induced dopaminergic neurodegeneration in mice. Importantly, the neuroprotective effect of Chuanxiong Chatiao pulvis against dopaminergic neurodegeneration may be associated with its strong antioxidant capacity in vivo.