Effect of acupuncture combined with hypothermia on MAPK/ERK pathway and apoptosis related factors in rats with cerebral ischemia reperfusion injury

Yaping LIN; Qin LIU; Chutao CHEN; Wen CHEN; Heng XIAO; Qianyun YANG; Haomei TIAN

ABSTRACT

Objective:

To observe effect of acupuncture combined with hypothermia therapy on MAPK/ERK pathway and apoptosis related factorsin rats suffered cerebral ischemia reperfusion and to explore underlying mechanisms.

Methods:

Middle cerebral artery ischemia model were established.Ninety SD rats were randomly assigned into a blank group,a control group,a model group,an acupuncture group,a mild hypothermia group,and an acupuncture with hypothermia group.After 72 h treatment,nervefunction defect scores were observed,and infarction area percent was detected by 2,3,5-triphenyl-2H-tetrazolium chloride (TTC) staining;expressions of Bcl-2 and Bax were examined by immunohistochemistry;apoptotic cells were detected by TUNEL assay;and expression levels of phospho-mitogen-activated protein kinase(p-MEK2) and phospho-extracellular signal regulated kinase 1/2 (p-ERK1/2) in the rats' hippocampus ischemic side were determined by Western blot.

Results:

In the rats of the model group,the neural function defect scores,the infarction area percent,the expression level of Bax,and apoptotic cells increased,while the level of Bcl-2 decreased significantly.The level of p-MEK2 and p-ERK1/2 increased obviously compared with the blank and control groups (P＜0.05 or P＜0.01).After treatment with acupuncture and hypothermia,the neural function defect scores,infarction area percent,and the level ofBax,apoptotic cells and the levels of p-MEK2 and p-ERK1/2 were significantly decreased,while the level of Bcl-2 in the treatment group was significantly elevated (P＜0.05 or P＜0.01) compared with the model group.Compared with the acupuncture group or the hypothermia group,the neural function defect scores and the levels of p-MEK2 and p-ERK1/2 in the acupuncture combined with hypothermia group were significantly reduced (P＜0.05 or P＜0.01).

Conclusion:

Acupuncture and hypothermia therapy can improve cerebral function,and reduce the cerebral injury through down-regulation of Bax level,and up-regulation of Bcl-2 level,which is related to reducing the levels of p-MEK2 and p-ERK1/2.The therapeutic effects on cerebral ischemia reperfusion injury for combination of acupuncture with hypothermia are better than those with single application of acupuncture or hypothermia.