Anti-apoptotic effect of Shudipingchan granule in the substantia nigra of rat models of Parkinson's disease.
Anti-apoptotic effect of Shudipingchan granule in the substantia nigra of rat models of Parkinson's disease.
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DOI：
10.4103/1673-5374.193242
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发表时间：
2016-10
影响因子：
6.1
通讯作者：
Yang XM
中科院分区：
文献类型：
--
作者：
Ye Q;Yuan XL;He J;Zhou J;Yuan CX;Yang XM
左旋多巴是治疗帕金森病的金标准。然而，尽管它减轻了临床症状，但它不能延迟多巴胺能神经元的进行性凋亡或长期预防运动并发症。本研究采用6-羟基多巴胺（6-hydroxydopamine，6-OHDA）注射于大鼠黑质腹侧被盖区（ventral tegmental area）建立帕金森病（Parkinson's disease，PD）模型，观察舒地平颤颗粒对PD模型大鼠神经元凋亡的影响。腹腔注射左旋多巴20 mg/kg，每日2次，同时灌胃或不灌胃舒迪平产颗粒7.5 mL/kg，每日2次，共4周。长期使用左旋多巴通过激活细胞外信号调节激酶途径和下游凋亡因子加速黑质细胞凋亡并恶化行为症状。舒地平产颗粒与左旋多巴合用可降低磷酸化细胞外信号调节激酶1/2和Bax的表达，增加酪氨酸羟化酶和Bcl-2的表达，减少黑质细胞凋亡，明显改善运动障碍。说明舒地平颤颗粒通过抑制细胞外信号调节激酶的过度磷酸化和下调抗凋亡基因的表达来抑制神经细胞凋亡。舒地平颤颗粒与左旋多巴合用，可有效减轻帕金森病的症状。
Levodopa is the gold-standard treatment for Parkinson's disease. However, although it alleviates the clinical symptoms, it cannot delay the progressive apoptosis of dopaminergic neurons or prevent motor complications in the long term. In the present study, we investigated the effect of Shudipingchan granule on neuronal apoptosis in a rat model of Parkinson's disease, established by injecting 6-hydroxydopamine into the substantia nigra pars compacta and ventral tegmental area. We then administered levodopa (20 mg/kg intraperitoneally, twice daily) with or without Shudipingchan granule (7.5 mL/kg intragastrically, twice daily), for 4 weeks. The long-term use of levodopa accelerated apoptosis of nigral cells and worsened behavioral symptoms by activating the extracellular signal-regulated kinase pathway and downstream apoptotic factors. However, administration of Shudipingchan granule with levodopa reduced expression of phosphorylated extracellular signal-regulated kinase 1/2 and Bax, increased tyrosine hydroxylase and Bcl-2, reduced apoptosis in the substantia nigra, and markedly improved dyskinesia. These findings suggest that Shudipingchan granule suppresses neuronal apoptosis by inhibiting the hyperphosphorylation of extracellular signal-regulated kinase and downregulating expression of anti-apoptotic genes. Shudipingchan granule, used in combination with levodopa, can effectively reduce the symptoms of Parkinson's disease.