Effects of autophagy on the protection of minocycline against cerebral ischemia-reperfusion injury in rats

doi:10.12092/j.issn.1009-2501.2019.07.002

Abstract

Abstract:

AIM: To investigate the effects of autophagy on the protection of minocycline against cerebral ischemia-reperfusion injury in rats. METHODS: Minocycline or Trimethyl adenine was injected to assess the neural function after the middle cerebral artery occlusion (MCAO) model established. The infarct volume was dertemined by TTC staining method at 24h after reperfusion. The ultrastructure of neurone and the quantity changes of autophagic vacuoles were observed by using transmission electron microscopy (TEM). The expression of protein LC3Ⅱ, Beclin1 and p62 were determined by Western blot. RESULTS:Minocycline (22.5 mg/kg, 45 mg/kg) significantly reduced rat nerve function scores and the cerebral infarction volume, while improved the expression of autophagy related proteins LC3Ⅱ and Beclin1 and increased the number of autophagosome and degradation of p62. Minocycline(90 mg/kg) could further increase the expression of LC3Ⅱ and Beclin1, with improvement of neural function and increase of infarct volume. Whereas the neuroprotective effects of minocycline(45 mg/kg) was reversed by the autophagy inhibitor 3-MA. CONCLUSION: Low dose minocycline attenuates cerebral ischemia reperfusion injury in rats, which might be mediated by up-regulating the protein LC3Ⅱand Beclin1 expression and promoting the degradation of p62/SQSTM l and then inducing autophagy; High dose minocycline aggravates cerebral ischemia reperfusion injury in rats by possible over activation of autophagy.

Key words: autophagy, minocycline, cerebral ischemia-reperfusion injury

CLC Number:

R965.2
R54

XIAO Shigeng, DONG Wenbin, YE Xiaodi, CHEN Aiying, CHENG Min, MIAO Yunping, ZHENG Gaoli. Effects of autophagy on the protection of minocycline against cerebral ischemia-reperfusion injury in rats[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2019, 24(7): 730-736.

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