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针刺抑制哺乳动物雷帕霉素靶蛋白,促进自噬,并减轻大鼠出血性中风模型的神经功能缺损。

Acupuncture inhibits mammalian target of rapamycin, promotes autophagy and attenuates neurological deficits in a rat model of hemorrhagic stroke.

机构信息

Department of Acupuncture and Moxibustion, Tongde Hospital of Zhejiang Province, Hangzhou, China.

Zhejiang Academy of Traditional Chinese Medicine, Hangzhou, China.

出版信息

Acupunct Med. 2022 Feb;40(1):59-67. doi: 10.1177/09645284211028873. Epub 2021 Jul 20.

Abstract

BACKGROUND

Intracerebral hemorrhage (ICH) accounts for approximately 15% of all stroke cases. Previous studies suggested that acupuncture may improve ICH-induced neurological deficits. Therefore, we investigated the effects of acupuncture on neurological deficits in an animal model of ICH.

METHODS

Adult male Sprague-Dawley rats were injected with autologous blood (50 μL) into the right caudate nucleus. Additional rats underwent sham surgery as controls. ICH rats either received acupuncture (GV20 through GB7 on the side of the lesion) or sham acupuncture (1 cm to the right side of the traditional acupuncture point locations). Some ICH rats received acupuncture plus rapamycin injection into the right lateral ventricle. Neurological deficits in the various groups were assessed based on composite neurological score. The perihemorrhagic penumbra was analyzed by histopathology following hematoxylin-eosin staining. Levels of autophagy-related proteins light chain (LC)3 and p62 as well as of mammalian target of rapamycin (mTOR)-related proteins, and phosphorylated (p)-mTOR and p-S6K1 (ribosomal protein S6 kinase beta-1), were assessed by Western blotting.

RESULTS

Acupuncture significantly improved composite neurological scores 7 days after ICH (17.7 ± 1.49 vs 14.8 ± 1.32, p < 0.01). Acupuncture augmented autophagosome and autolysosome accumulation based on transmission electron microscopy. Acupuncture significantly increased expression of LC3 (p < 0.01) but decreased expression of p62 (p < 0.01). Acupuncture also reduced levels of p-mTOR and p-S6K1 (both p < 0.01).

CONCLUSION

Acupuncture improved neurological deficits in a rat model of ICH, possibly by inhibiting the mTOR pathway and activating autophagy.

摘要

背景

脑出血(ICH)约占所有中风病例的 15%。先前的研究表明,针刺可能改善 ICH 引起的神经功能缺损。因此,我们研究了针刺对 ICH 动物模型中神经功能缺损的影响。

方法

成年雄性 Sprague-Dawley 大鼠将自体血(50μL)注入右侧尾状核。另外一些大鼠接受假手术作为对照。ICH 大鼠接受针刺(病变侧的 GV20 和 GB7)或假针刺(传统针刺点右侧 1cm)。一些 ICH 大鼠接受针刺加雷帕霉素侧脑室注射。根据复合神经评分评估各组的神经功能缺损。苏木精-伊红染色后通过组织病理学分析出血周围半影区。通过 Western blot 评估自噬相关蛋白 LC3 和 p62 以及哺乳动物雷帕霉素靶蛋白(mTOR)相关蛋白,以及磷酸化(p)-mTOR 和 p-S6K1(核糖体蛋白 S6 激酶 beta-1)的水平。

结果

针刺治疗可显著改善 ICH 后 7 天的复合神经评分(17.7±1.49 比 14.8±1.32,p<0.01)。针刺治疗通过透射电镜增强自噬体和自噬溶酶体的积累。针刺治疗显著增加 LC3 的表达(p<0.01),但减少 p62 的表达(p<0.01)。针刺治疗还降低了 p-mTOR 和 p-S6K1 的水平(均 p<0.01)。

结论

针刺治疗可改善 ICH 大鼠的神经功能缺损,可能通过抑制 mTOR 通路和激活自噬。

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