Study on the mechanism of autophagy regulation in neural repair in rats with subacute ischemic stroke
ZHOU Ping1 XU Weijie1 ZANG Rui2 LI Youkuan1 WU Yuming1#br#
1.Human Anatomy Teaching and Research Section, Kunming Health Vocational College, Yunnan Province, Kunming 650600, China;
2.Department of Emergency, Zhaotong Hospital of Traditional Chinese Medicine, Yunnan Province, Zhaotong 657000, China
Abstract:Objective To explore the mechanism of autophagy regulation in neural repair in rats with subacute ischemic stroke. Methods A total of 96 SPF male SD rats aged eight weeks old from 250-280 g were divided into sham operation group, model group, Rapamycin group, and 3-methyladenine group according to random number table method, with 24 rats in each group. The model group, Rapamycin group, and 3-methyladenine group were used to establish the left middle cerebral artery occlusion reperfusion model of rats, and Zea-Longa score of 1-3 points indicated that the model was successful. In the sham operation group, all other steps were the same except the insertion of the thread plug. Rapamycin group was given Rapamycin (8 ng dissolved in 5 μl 0.1%DMAO), 3-methyladenine group was given 3-methyladenine (100 μg dissolved in 5 μl 0.1%DMAO), sham operation group and model group were given 5 μl 0.1%DMAO solution, all pumped through the lateral ventricle. After injection, the four groups kept the needle for 5 minutes, once a day, for seven consecutive days. At the end of the experiment, the changes of neural function and autophagy related indexes in the penumbra area of rats with subacute ischemic stroke were investigated by modified neurological severity score (mNSS), TTC staining, fluorescence staining, Western blot, and immunofluorescence. Results The mNSS, percentage of the infarct volume, percentage of microtubule-associated protein light chain 3 (LC3) positive cells, Beclin-1, and LC3-Ⅱ/LC3-Ⅰ protein levels in model group were higher than those in sham group, and the proportion of neuronal nuclei (NeuN) positive cells was lower than sham group, the differences were statistically significant (P < 0.05 or P < 0.01). The mNSS and percentage of the infarct volume of Rapamycin group were lower than those of model group, proportion of LC3 positive cells, Beclin-1, and LC3-Ⅱ/LC3-Ⅰ protein level, proportion of NeuN positive cells were higher than those of model group, the differences were statistically significant (P < 0.05 or P < 0.01). The mNSS and proportion of the infarct volume of 3-methyladenine group were higher than those of model group, proportion of LC3 positive cells, Beclin-1, and LC3-Ⅱ/LC3-Ⅰ protein level, proportion of NeuN positive cells were lower than those of model group, the differences were statistically significant (P < 0.05 or P < 0.01). Conclusion Activation of autophagy in rats with subacute ischemic stroke has a neuroprotective effect, while inhibition of autophagy increases the neurological damage. Moderate autophagy may be the key to the study of ischemic stroke.
周平1 徐伟杰1 臧瑞2 李友宽1 武煜明1. 自噬调控在大鼠缺血性脑卒中亚急性期神经修复中的机制研究[J]. 中国医药导报, 2022, 19(22): 20-24.
ZHOU Ping1 XU Weijie1 ZANG Rui2 LI Youkuan1 WU Yuming1. Study on the mechanism of autophagy regulation in neural repair in rats with subacute ischemic stroke. 中国医药导报, 2022, 19(22): 20-24.