聚肌苷酸聚胞苷酸对高血脂大鼠脑缺血/再灌注后Bcl-2和Bax表达的影响及神经保护作用

doi:10.16098/j.issn.0529-1356.2023.02.007

摘要/Abstract

摘要：

目的观察聚肌苷酸聚胞苷酸(Poly-IC)处理对高血脂大鼠脑缺血/再灌注（I/R）损伤后Bcl-2和Bax表达的影响，同时检测脑梗死灶、血脑屏障通透性和行为损伤症状，探讨其对高血脂合并脑I/R损伤是否发挥神经保护作用。方法高血脂大鼠随机分为脑I/R组、Poly-IC预处理组、Poly-IC后处理组和假手术（Sham）组，每组20只。0~4分神经行为评分记录各组大鼠的神经行为表现，伊文思蓝染色法检测各组大鼠血脑屏障通透性，TTC染色法观察各组大鼠脑组织梗死情况，TUNEL染色法测神经细胞的凋亡情况，Western blotting观察Bcl-2 和Bax相对表达水平。结果与sham组比较，I/R 组神经行为损伤症状严重，评分明显升高 (P<0.05)。而Poly-IC 预处理和后处理组评分较 I/R组均明显降低（P<0.05)。伊文思蓝染色结果显示，I/R组较sham组血脑屏障通透性明显增高（P<0.05），而Poly-IC预处理或后处理可明显改善血脑屏障通透性（P<0.05）。脑梗死体积检测结果显示，sham组未见梗死灶均匀红染，而I/R组脑组织可见白色梗死区。与I/R组比较，Poly-IC预处理和后处理组梗死灶体积均明显缩小（P<0.05）。I/R组大鼠大脑皮质内细胞凋亡指数较sham组显著升高（P<0.05），而Poly-IC预处理和后处理组大鼠大脑皮质内细胞凋亡指数较I/R组均明显降低（P<0.05）。与sham组比较，I/R组Bax表达明显升高（P<0.05），Bcl-2表达明显降低（P<0.05）。与I/R组比较，Poly-IC预处理和后处理组Bax表达均明显降低（P<0.05），Bcl-2表达明显升高（P<0.05）。结论 Poly-IC预处理或后处理可改善神经行为损伤症状，减轻血脑屏障损害，缩小脑梗死体积，降低神经细胞凋亡指数，对高血脂大鼠脑I/R损伤起到神经保护作用；该保护作用可能与Bcl-2和Bax表达水平改变有关。

关键词: 高血脂, 脑缺血/再灌注, 聚肌苷酸聚胞苷酸, B淋巴细胞瘤-2, Bcl-2相关X蛋白, 原位缺口末端标记, 大鼠

Abstract:

Objective To observe the effect of polyinosinic-polycytidylic acid (Poly-IC) treatment on the expressions of Bcl-2 and Bax after cerebral ischemia-reperfusion （I/R）injury in hyperlipidemia rats, and to detect the cerebral infarction, blood-brain barrier permeability and behavioral injury symptoms, to explore the neuroprotective effect of Poly-IC treatment on cerebral I/R injury in hyperlipidemia rats. Methods Hyperlipidemia rats were randomly divided into cerebral I/R group, Poly-IC pretreatment group, Poly-IC post-treatment group and sham operation group, 20 rats in each group. Neurobehavioral performance of rats in each group was recorded according to neurobehavioral score of 0-4 points. Blood-brain barrier permeability of rats in each group was detected by Evans blue staining. TTC staining was used to observe the cerebral infarction in each group. Apoptotic cells in the cerebral cortex of rats in each group was observed by TUNEL staining. The relative expression levels of Bcl-2 and Bax were determined by Western blotting. Results Compared with the sham group, the symptoms of neurobehavioral damage in the I/R group were serious and the score increased significantly(P<0.05). The scores of Poly-IC pretreatment and post-treatment groups were significantly lower than that of I/R group(P<0.05). Evans blue staining result showed that the blood-brain barrier permeability of the I/R group was significantly higher than that of the sham group (P<0.05), and Poly-IC pretreatment or post-treatment could significantly reduce the blood-brain barrier permeability(P<0.05). No infarct was observed in the sham group with uniform red staining, while white infarct was observed in the brain tissue of the I/R group. Compared with the I/R group, the volume of infarct in both Poly-IC pretreatment and post-treatment groups reduced significantly (P<0.05). The apoptosis index in cerebral cortex of rats in I/R group was significantly higher than that in sham group (P<0.05), while the apoptosis index in Poly-IC pretreatment or post-treatment group was significantly lower than that in I/R group(P<0.05). The result of Western blotting showed that, compared with the sham group, the expression of Bax in the I/R group was significantly increased(P<0.05), the expression of Bcl-2 was significantly decreased(P<0.05). Compared with the I/R group, the expression of Bax in the Poly-IC pretreatment or post-treatment group reduced significantly(P<0.05), the expression of Bcl-2 increased significantly(P<0.05). Conclusion Poly-IC pretreatment or post-treatment can improve the symptoms of neurobehavioral injury, reduce the damage of blood-brain barrier, reduce the volume of cerebral infarction, decrease the apoptosis index of nerve cells, play a neuroprotective effect on cerebral ischemia reperfusion injury in rats with hyperlipidemia, and this protective effect may be related to the change of Bcl-2 and Bax expression levels.

Key words:

Hyperlipidemia, Cerebral ischemia-reperfusion, Polyinosinic-polycytidylic acid, B-cell lymphoma-2, Bcl-2 assaciated X protein, Terminal UTP nickend labeling, Rat

中图分类号:

R322.8

高赛红张小良杨迎春乔海兵 . 聚肌苷酸聚胞苷酸对高血脂大鼠脑缺血/再灌注后Bcl-2和Bax表达的影响及神经保护作用[J]. 解剖学报, 2023, 54(2): 175-180.

GAO Sai-hong ZHANG Xiao-liang YANG Ying-chun QIAO Hai-bing .

Polyinosinic-polycytidylic acid affecting the expressions of Bcl-2 and Bax after cerebral ischemia-reperfusion in hyperlipidemic rats and its neuroprotective effect

[J]. Acta Anatomica Sinica, 2023, 54(2): 175-180.

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