[Effect of manual acupuncture on expression of BDNF/TrkB/ERK/CREB signaling in infarcted tissue of cerebral ischemia rats]
- PMID: 35218623
- DOI: 10.13702/j.1000-0607.20210048
[Effect of manual acupuncture on expression of BDNF/TrkB/ERK/CREB signaling in infarcted tissue of cerebral ischemia rats]
Abstract
Objective: To observe the effect of acupuncture on the expression of cortical brain-derived neurothrophic factor (BDNF) and tyrosine kinase receptor B (TrkB) mRNAs, and phosphorylated extracellular regulated protein kinases (p-ERK) 1/2 and phosphorylated cAMP response element binding protein (p-CREB) proteins in cerebral ischemia (CI) rats, so as to explore its neuroprotective mechanism on ischemic brain tissue.
Methods: Thirty male SD rats were randomly divided into sham-operation (control), model and acupuncture groups, with 10 rats in each group. The CI model was established by occlusion of the left middle cerebral artery (MCAO) using thread embolization method. Manual acupuncture was applied to"Baihui"(GV20),"Quchi"(LI11),"Neiguan"(PC6),"Hegu"(LI4),"Zusanli"(ST36),"Sanyinjiao"(SP6) and"Shenmai"(BL62) once daily, 6 days a week for 2 weeks. The modified neurological severity score (mNSS) including motor, sensation, balance, and neural reflex functions (0 point, normal; 18 points, maximal deficit) was used to assess the neurological impairment state. The expression levels of p-ERK 1/2 and p-CREB proteins, and BDNF and TrkB mRNAs in the ischemic cerebral cortex were measured by Western blot and real-time fluorescence quantitative PCR, respectively.
Results: The mNSS was significantly increased on day 1, 7 and 14 in the model group compared with the control group (P<0.01), and evidently decreased on day 14 in the acupuncture group in contrast to the model group (P<0.05). The expression levels of BDNF and TrkB mRNAs, and p-ERK1, p-ERK2 and p-CREB proteins on day 7 and 14 were significantly lower in the model group than in the control group (P<0.001). Following acupuncture treatment, the down-regulated expression levels of the two genes and the three proteins on day 14 were reversed (P<0.001, P<0.05, P<0.01).
Conclusion: Acupuncture may promote neurological recovery in rats with cerebral ischemia, which may be related to its function in up-regulating the activities of BDNF/TrkB-ERK-CREB signaling in the cerebral cortex on the ischemic side.
目的:观察针刺对脑缺血大鼠皮层脑源性神经营养因子(BDNF)、酪氨酸激酶受体B(TrkB)及磷酸化细胞外调节蛋白激酶(p-ERK)1/2、磷酸化cAMP反应元件结合蛋白(p-CREB)表达的影响,探讨针刺改善缺血性脑卒中的神经保护机制。方法:将30只SD大鼠随机分为假手术组、模型组、针刺组,每组10只。用线栓法行左侧大脑中动脉阻塞术以建立脑缺血大鼠模型。针刺组针刺“百会”“曲池”“内关”“合谷”“足三里”“三阴交”“申脉”,1次/d,连续6 d,休息1 d,共干预2周。于造模后1、7、14 d对大鼠进行神经功能缺损量表(mNSS)评分评估,Western blot法检测缺血侧大脑皮层内p-CREB、p-ERK1/2蛋白的表达,实时荧光定量PCR法检测缺血侧大脑皮层BDNF、TrkB mRNA的表达。结果:与同时点假手术组比较,模型组大鼠造模后1、7、14 d时mNSS评分均明显升高(P<0.01),造模后7、14 d时梗死侧大脑皮层中p-CREB、p-ERK1、p-ERK2蛋白及BDNF、TrkB mRNA相对表达量均明显下降(P<0.001)。与同时点模型组比较,针刺组大鼠造模后14 d时神经功能评分降低(P<0.05),造模后7、14 d时梗死区域皮层BDNF mRNA的表达明显升高(P<0.01,P<0.001),造模后14 d时梗死区域皮层p-CREB、p-ERK1、p-ERK2蛋白及TrkB mRNA相对表达量均明显升高(P<0.001,P<0.05,P<0.01)。结论:针刺可能是通过上调大脑缺血侧皮层中p-CREB、p-ERK1、p-ERK2蛋白及BDNF、TrkB mRNA表达,促进脑缺血大鼠神经功能恢复。.
Keywords: Acupuncture; BDNF/TrkB-ERK-CREB signaling pathway; Cerebral ischemia; Neurological function.
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