Duan Sijin, Wang Tian, Zhang Jianqiao, Li Minmin, Lu Chengwen, Wang Lijie, Zou Yan, Fu Fenghua
School of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation, Yantai University, Yantai, 264005, People's Republic of China.
Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Yantai University, Yantai, 264005, People's Republic of China.
BMC Complement Altern Med. 2017 Jan 5;17(1):19. doi: 10.1186/s12906-016-1516-z.
Ischemic stroke is the third leading cause of death in adults worldwide and is the first leading cause of long-term disability. Neurogenesis plays an important role in promoting behavioral recovery after stroke. Huatuo Zaizao pill (HT), a traditional Chinese medicine, has been used clinically in China to promote the rehabilitation after stroke, but the underlying mechanism of action was still unclear. This study is to investigate the effects of HT on the functional recovery in a rat model of cerebral ischemia-reperfusion (I/R) injury, and the potential molecular mechanisms.
Rats were randomly divided into sham, model with cerebral I/R injury, or HT-treated groups, then administered orally with vehicle (for the sham and model group) or HT (0.5, 1.0, or 2.0 mg/kg) respectively, for 3 or 7 days. Functional recovery was assessed by cylinder test, beam walking test, and adhesive test. Neurogenesis was investigated by double immunofluorescence staining for 5-ethynyl-2-deoxyuridine (EdU) and neuronal nuclear protein (NeuN). The proteins of kinase A (PKA), cAMP response element-binding protein (CREB), and brain-derived neurotrophic factor (BDNF) were assayed by western blotting. The level of BDNF mRNA was evaluated by RT-PCR.
Compared with the model group, treatment with HT significantly promoted functional recovery in I/R injured rats (p < 0.05 or p < 0.01). The generation of new neurons was increased in the HT groups. HT treatment for 3 days increased the level of BDNF mRNA in I/R injured rats. Expression of PKA, phosphorylated CREB, and BDNF were significantly (p < 0.05) increased with the 7-day HT treatment.
These results indicated that HT treatment could promote functional recovery after stroke. HT enhanced the expression of BDNF and increased the level of neurogenesis in cerebral I/R animal, which might be associated with the functional recovery.
缺血性中风是全球成年人第三大死因，也是长期残疾的首要原因。神经发生在促进中风后行为恢复中起重要作用。华佗再造丸（HT）是一种中药，在中国临床上已用于促进中风后的康复，但其潜在作用机制仍不清楚。本研究旨在探讨HT对脑缺血再灌注（I/R）损伤大鼠模型功能恢复的影响及其潜在分子机制。
将大鼠随机分为假手术组、脑I/R损伤模型组或HT治疗组，然后分别口服溶剂（假手术组和模型组）或HT（0.5、1.0或2.0mg/kg），持续3或7天。通过圆筒试验、横梁行走试验和黏附试验评估功能恢复情况。通过对5-乙炔基-2'-脱氧尿苷（EdU）和神经元核蛋白（NeuN）进行双重免疫荧光染色来研究神经发生。通过蛋白质印迹法检测蛋白激酶A（PKA）、环磷酸腺苷反应元件结合蛋白（CREB）和脑源性神经营养因子（BDNF）的蛋白水平。通过逆转录聚合酶链反应（RT-PCR）评估BDNF mRNA水平。
与模型组相比，HT治疗显著促进了I/R损伤大鼠的功能恢复（p<0.05或p<0.01）。HT组新神经元的生成增加。HT治疗3天可提高I/R损伤大鼠的BDNF mRNA水平。HT治疗7天可显著（p<0.05）提高PKA、磷酸化CREB和BDNF的表达。
这些结果表明，HT治疗可促进中风后的功能恢复。HT增强了BDNF的表达，增加了脑I/R动物的神经发生水平，这可能与功能恢复有关。
