仙茅苷对脊髓损伤大鼠的神经保护作用研究
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篇名: | 仙茅苷对脊髓损伤大鼠的神经保护作用研究 |
TITLE: | Study on the neuroprotective effect of curculigoside on rats with spinal cord injury |
摘要: | 目的 基于人第10号染色体缺失的磷酸酶及张力蛋白同源基因诱导的假定激酶1(PINK1)/E3泛素连接酶Parkin信号通路探讨仙茅苷(CUR)对脊髓损伤(SCI)大鼠的神经保护作用。方法以雄性SD大鼠为对象,随机选取15只作为假手术组,其余大鼠以脊髓撞击法建立SCI模型并将造模成功的大鼠分为模型组、CUR低剂量组(36mg/kgCUR,灌胃)、CUR高剂量组(72mg/kgCUR,灌胃)、CUR高剂量+3-甲基腺嘌呤(3-MA)组(72mg/kgCUR,灌胃+20mg/kg自噬抑制剂3-MA,腹腔注射),每组15只。各组大鼠给予相应药液/生理盐水,每天1次,持续28d。于给药后第14、28天对各组大鼠进行Basso-Beattie-Bresnahan(BBB)评分和Rivlin斜板实验;观察各组大鼠脊髓组织的病理学变化,检测其脊髓组织的细胞凋亡情况、氧化应激因子[丙二醛(MDA)、超氧化物歧化酶(SOD)、谷胱甘肽(GSH)]水平以及脑源性神经营养因子(BDNF)、胶质细胞原纤维酸性蛋白(GFAP)、PINK1、Parkin、p62、微管相关蛋白轻链3(LC3)蛋白的表达水平。结果与假手术组比较,模型组大鼠脊髓组织可见明显的水肿和出血,并伴有大量炎症细胞浸润,其BBB评分和斜板角度,SOD和GSH水平,BDNF、PINK1、Parkin蛋白的表达水平和LC3Ⅱ/Ⅰ比值均显著降低,脊髓组织的细胞凋亡率、MDA水平和GFAP、p62蛋白的表达水平均显著升高(P<0.05);与模型组比较,各药物组大鼠脊髓组织水肿、出血、炎症细胞浸润均有所减少,上述各定量指标均显著改善(P<0.05);3-MA可显著逆转CUR对上述指标的改善作用(P<0.05)。结论CUR能促进SCI大鼠神经功能和运动功能的恢复,改善其脊髓组织病理损伤并抑制细胞凋亡,上述作用可能与CUR可激活PINK1/Parkin信号通路介导的线粒体自噬有关。 |
ABSTRACT: | OBJECTIVE To investigate the neuroprotective effect of curculigoside (CUR) on rats with spinal cord injury (SCI) based on phosphatase and tensin homologue deleted on chromosome ten gene-induced putative kinase 1 (PINK1)/E3 ubiquitin ligase Parkin signaling pathway. METHODS Taking male SD rats as subjects, 15 rats were randomly selected as sham operation group; the rest rats were chosen to establish SCI model by spinal cord impact method, and then were divided into model group, CUR low-dose group (36 mg/kg CUR, gavage), CUR high-dose group (72 mg/kg CUR, gavage) and CUR high-dose+3- methyladenine (3-MA) group (72 mg/kg CUR, gavage+20 mg/kg autophagy inhibitor 3-MA, intraperitoneal injection), with 15 rats in each group. Rats in each group were given corresponding liquid/normal saline, once a day, for 28 consecutive days. Basso- Beattie-Bresnahan (BBB) score and Rivlin inclined plate experiment were performed on the 14th and 28th day after administration; the pathological changes of spinal cord tissue in rats were observed in each group; the apoptosis of spinal cord tissue, the levels of oxidative stress factors [malondialdehyde (MDA), superoxide dismutase (SOD), glutathione (GSH)], and the protein expressions of brain-derived neurotrophic factor (BDNF), glial fibrillary acidic protein (GFAP), PINK1, Parkin, p62 and microtubule- associated protein light chain 3 (LC3) were all determined. RESULTS Compared with the sham operation group, obvious edema and bleeding in the spinal cord tissue of rats were observed in the model group, accompanied by a large number of inflammatory cell infiltration; BBB score and inclined plate angle, SOD and GSH levels, the protein expressions of BDNF, PINK1 and Parkin, and LC3Ⅱ/Ⅰ ratio were significantly reduced; the apoptosis rate, MDA level, the protein expressions of GFAP and p62 in spinal cord tissue were significantly increased (P<0.05). Compared with the model group, the edema, bleeding and infiltration of inflammatory cells in the spinal cord tissue of rats were reduced in the administration groups, and the above quantitative indicators had been significantly improved (P<0.05); 3-MA could significantly reverse the improvement effects of the above indexes by CUR (P<0.05). CONCLUSIONS CUR can promote the recovery of neurological and motor functions in SCI rats, improve the pathological injury of the spinal cord and inhibit apoptosis, which may be related to mitochondrial autophagy mediated by activating the PINK1/Parkin signaling pathway. |
期刊: | 2024年第35卷第12期 |
作者: | 刘娜;黄培培;杨静;李亚菲 |
AUTHORS: | LIU Na,HUANG Peipei,YANG Jing,LI Yafei |
关键字: | 仙茅苷;脊髓损伤;神经保护;PINK1/Parkin信号通路;线粒体自噬 |
KEYWORDS: | curculigoside; spinal cord injury; neuroprotection; PINK1/Parkin signaling pathway; mitochondrial autophagy |
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