TY - JOUR
AB - Ischemic stroke seriously threatens human health and creates a large social burden. The present study investigated whether tissue inhibitor of metalloproteinases‑3 (TIMP3) prevented cerebral ischemia/reperfusion (I/R), with the aim to explore the underlying mechanism. A transient middle cerebral artery occlusion model was conducted in mice, and oxygen glucose deprivation and reoxygenation (OGD/R) was investigated in PC12 cells to mimic cerebral ischemia‑reperfusion injury (CIRI). Western blotting was used to determine the expression of TIMP3, Bax, Bcl‑2 and AKT. TUNEL was used to detect apoptosis in cerebral tissues or cultured PC12 cells. Expression levels of reactive oxygen species (ROS), superoxide dismutase (SOD) and malondialdehyde (MDA) were detected to reveal oxidative stress. The results demonstrated that TIMP3 expression was significantly decreased after I/R in vivo or OGD/R in vitro, and the number of TUNEL‑positive cells was reduced by the overexpression of TIMP3. The attenuation of Bax/Bcl‑2 ratio in OGD/R‑induced PC12 cells suppressed the expression levels of ROS and MDA; while also elevating SOD activity in the OGD/R‑induced neurocytes in vitro. In addition, TIMP3‑overexpression reversed the downregulation of phosphorylated‑AKT (Thr308 and Ser473) in OGD/R‑treated PC12 cells. However, the anti‑apoptotic and anti‑oxidative stress roles of TIMP3 in OGD/R‑induced PC12 cells were partially abolished after treatment with the AKT inhibitor, AZD5363. Overall, TIMP3 exerted an anti‑apoptotic and anti‑oxidative stress role in CIRI through the AKT pathway, which may be a potential therapeutic target for the treatment of CIRI.
AD - Department of Imaging, Xingtai People's Hospital, Xingtai, Hebei 054001, P.R. China
Department of Imaging, Xingtai Orthopedic Hospital, Xingtai, Hebei 054001, P.R. China
Department of Cardiothoracic Surgery, Xingtai People's Hospital, Xingtai, Hebei 054001, P.R. China
Department of Neurology, Xingtai People's Hospital, Xingtai, Hebei 054001, P.R. China
AU - Meng,Linglei
AU - Zhang,Yongting
AU - Li,Demao
AU - Shang,Xinfang
AU - Hao,Xuejia
AU - Chen,Xin
AU - Gao,Fengxiao
DA - 2021/09/01
DO - 10.3892/etm.2021.10405
IS - 3
JO - Exp Ther Med
KW - cerebral ischemia‑reperfusion injury
tissue inhibitor of metalloproteinases‑3
AKT pathway
oxidative stress
TUNEL
PY - 2021
SN - 1792-0981
1792-1015
SP - 973
ST - TIMP3 attenuates cerebral ischemia/reperfusion‑induced apoptosis and oxidative stress in neurocytes by regulating the AKT pathway
T2 - Experimental and Therapeutic Medicine
TI - TIMP3 attenuates cerebral ischemia/reperfusion‑induced apoptosis and oxidative stress in neurocytes by regulating the AKT pathway
UR - https://doi.org/10.3892/etm.2021.10405
VL - 22
ER -