Department of Pharmacy, Zhejiang Integrated Traditional and Western Medicine Hospital, Hangzhou, Zhejiang 310003, P.R. China.
School of Clinical Medicine, Wannan Medicial College, Wuhu, Anhui 241002, P.R. China.
Mol Med Rep. 2021 Apr;23(4). doi: 10.3892/mmr.2021.11936. Epub 2021 Mar 2.
Ischemic stroke, the third leading cause of disability globally, imposes a notable economic burden. Tetrandrine (Tet), which has been widely used clinically, exhibits potential protective effects against stroke. However, there has been little pre‑clinical research to evaluate the therapeutic effects of Tet on stroke. The present study investigated the beneficial effect of Tet on ischemia‑reperfusion (I/R) injury and its underlying mechanism in rats. Rats were subjected to occlusion of the middle cerebral artery, then treated with Tet (30 mg/kg/day, intraperitoneal) in the subacute phase for 7 days. In order to detect the effects of Tet on the behavior of rats, modified neurological severity score and longa behavior, grasping capability and inclined plane tests were conducted on days 1, 3 and 7 following cerebral ischemia. In addition, neuronal apoptosis in the cortex and hippocampus following ischemia was assessed by Nissl staining and TUNEL assay. Finally, oxidative stress was evaluated by measurement of free radicals and immunofluorescence staining of LC3 was used to assess autophagy. Tet improved neurological function and decreased infarct volume in I/R injury rats. Tet also prevented neuronal apoptosis in the cortex and hippocampus region. In addition, Tet protected against oxidative damage following ischemia, which was reflected by decreased levels of nitric oxide and malondialdehyde and increased levels of glutathione (GSH) and GSH peroxidase. In addition, the expression levels of the autophagy marker LC3 decreased in the Tet treatment group. In conclusion, Tet attenuated I/R‑induced neuronal damage in the subacute phase by decreasing oxidative stress, apoptosis and autophagy.
缺血性脑卒中是全球第三大致残原因，造成了显著的经济负担。汉防己甲素（Tet）在临床上广泛应用，具有潜在的抗脑卒中作用。然而，针对 Tet 治疗脑卒中的疗效，临床前研究甚少。本研究旨在探讨 Tet 对大鼠缺血再灌注（I/R）损伤的保护作用及其潜在机制。大鼠大脑中动脉阻塞后，于亚急性期每天腹腔内给予 Tet（30mg/kg）治疗 7 天。为了检测 Tet 对大鼠行为的影响，在脑缺血后第 1、3、7 天进行改良神经功能缺损评分和 Longa 行为、抓握能力和斜面试验。此外，通过尼氏染色和 TUNEL 检测评估皮质和海马区神经元凋亡。最后，通过自由基测定评估氧化应激，免疫荧光染色 LC3 评估自噬。Tet 改善了 I/R 损伤大鼠的神经功能，降低了梗死体积。Tet 还可预防皮质和海马区神经元凋亡。此外，Tet 可减轻缺血后氧化损伤，表现为一氧化氮和丙二醛水平降低，谷胱甘肽（GSH）和 GSH 过氧化物酶水平升高。此外，Tet 治疗组自噬标志物 LC3 的表达水平降低。总之，Tet 通过降低氧化应激、凋亡和自噬，减轻了 I/R 诱导的亚急性期神经元损伤。
