羟氯喹促进ERK1/2磷酸化减轻大鼠脑缺血再灌注损伤

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Abstract Objective: To evaluate the attenuation of hydroxychloroquine(HCQ) for cerebral ischemia reperfusion(I/R) injury induced by transient middle cerebral artery occlusion(MCAO) in rats and potential mechanisms. Methods: A total of 72 healthy male SD rats were randomly divided into 6 groups (n=12):control group, ischemiareperfusion group (group I/R), low dose HCQ pretreatment group (group HCQ250), medium dose HCQ pretreatment group (group HCQ500),high dose HCQ pretreatment group (group HCQ1000) and extracellular regulated protein kinase 1/2(ERK1/2) inhibitor U0126 pretreatment group (group U0126). MCAO was used to establish rat ischemic stroke model. Control group was the same as group I/R, but not occluded the middle cerebral artery; group I/R was reperfused after MCAO for 2 h; group HCQ250, group HCQ500, group HCQ1000 and group U0126 were injected with 8 μL 250 μmol/L, 500 μmol/L, 1 000 μmol/L and 1 000 μmol/L HCQ by lateral ventricle (LV) at 24 h, 48 h and 72 h, respectively, before MCAO, and U0126 group was injected with 8 μL of 1 000 μmol/L U0126 after 12 h each injection of HCQ. Brain tissues were collected by decollation after reperfusion 6 h, the expression of ERK1/2, pERK1/2, antiapoptotic factor Bcl2,proapoptotic factor cleaved caspase3,pCREB and pAkt was detected by Western blotting in ischemic penumbra. Neurological deficit score was measured and followed infarct volume was detection by TTC staining 24 h after reperfusion. Results: Compared with control group, neurological deficit score was reduced, infarct volume was magnified, the expression of pERK1/2, cleaved caspase3, pCREB, pAkt was increased, Bcl2 expression was decreased in group I/R , group HCQ250, group HCQ500, group HCQ1000 and group U0126(P<0.05). Compared with group I/R, neurological deficit score was enlarged, infarct volume was reduced, the expression of pERK1/2, Bcl2, pCREB, pAkt was increased, the expression of cleaved caspase3 was decreased in group HCQ1000 (P<0.05). However, compared with group HCQ1000, neurological deficit score was reduced, infarct volume was magnified, the expression of pERK1/2, Bcl2, pCREB, pAkt was decreased, the expression of cleaved caspase3 was increased in group U0126(P<0.05). Conclusion: Hydroxychloroquine may promote the expression of pERK1/2 and protects agaist cerebral ischemia through reperfusion injury through CREB/Akt signaling way in rats.

Received: 11 April 2018

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http://zzs.ujs.edu.cn/xbyxb/EN/ OR http://zzs.ujs.edu.cn/xbyxb/EN/Y2019/V29/I01/31

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