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[手动针刺对脑缺血大鼠梗死组织中BDNF/TrkB/ERK/CREB信号通路表达的影响]

[Effect of manual acupuncture on expression of BDNF/TrkB/ERK/CREB signaling in infarcted tissue of cerebral ischemia rats].

作者信息

Zhong Lu-Yu, Yu Tao, Wang Meng, Zhao Shan-Shan, Wang Si-Qi

机构信息

Department of Comprehensive Rehabilitation, National Clinical Research Center for Acupuncture and Moxibustion of Chinese Medicine, The First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin 300381, China.

出版信息

Zhen Ci Yan Jiu. 2022 Feb 25;47(2):135-40. doi: 10.13702/j.1000-0607.20210048.

DOI:10.13702/j.1000-0607.20210048
PMID:35218623
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 (<0.01), and evidently decreased on day 14 in the acupuncture group in contrast to the model group (<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 (<0.001). Following acupuncture treatment, the down-regulated expression levels of the two genes and the three proteins on day 14 were reversed (<0.001, <0.05, <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.

摘要

目的

观察针刺对脑缺血(CI)大鼠皮质脑源性神经营养因子(BDNF)和酪氨酸激酶受体B(TrkB)mRNA,以及磷酸化细胞外调节蛋白激酶(p-ERK)1/2和磷酸化环磷腺苷反应元件结合蛋白(p-CREB)蛋白表达的影响,以探讨其对缺血脑组织的神经保护机制。

方法

30只雄性SD大鼠随机分为假手术(对照)组、模型组和针刺组,每组10只。采用线栓法阻断左侧大脑中动脉(MCAO)建立CI模型。每天针刺“百会”(GV20)、“曲池”(LI11)、“内关”(PC6)、“合谷”(LI4)、“足三里”(ST36)、“三阴交”(SP6)和“申脉”(BL62)1次,每周6天,共2周。采用改良神经功能缺损评分(mNSS),包括运动、感觉、平衡和神经反射功能(0分,正常;18分,最大缺损)评估神经功能缺损状态。分别采用蛋白质免疫印迹法和实时荧光定量PCR法检测缺血皮质中p-ERK 1/2和p-CREB蛋白,以及BDNF和TrkB mRNA的表达水平。

结果

与对照组比较,模型组在第1、7和14天mNSS显著升高(<0.01);与模型组比较,针刺组在第14天mNSS明显降低(<0.05)。与对照组比较,模型组在第7和14天BDNF和TrkB mRNA,以及p-ERK1、p-ERK2和p-CREB蛋白的表达水平显著降低(<0.001)。针刺治疗后,第14天两个基因和三个蛋白下调的表达水平得到逆转(<0.001、<0.05、<0.01)。

结论

针刺可能促进脑缺血大鼠的神经功能恢复,这可能与其上调缺血侧大脑皮质BDNF/TrkB-ERK-CREB信号通路活性的作用有关。

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