| 武林娟,靳雅惠,高枫.桔皮素通过rno-miR-9a-5p/Notch通路促进脊髓损伤大鼠神经功能恢复.[J].中南医学科学杂志.,2026,(1):7-13. |
| 桔皮素通过rno-miR-9a-5p/Notch通路促进脊髓损伤大鼠神经功能恢复 |
| Tangeretin promotes neural function recovery in spinal cord injury rats through rno-miR-9a-5p/Notch pathway |
| 投稿时间：2025-04-27 修订日期：2025-10-23 |
| DOI：10.15972/j.cnki.43-1509/r.2026.01.002 |
| 中文关键词: 脊髓损伤 桔皮素 rno-miR-9a-5p Notch通路 神经功能恢复 |
| 英文关键词:SCI tangeretin rno-miR-9a-5p Notch pathway neurological recovery |
| 基金项目:国家自然科学基金资助项目(82460765) 作者简介:武林娟,硕士研究生,主治医师,研究方向为神经生物学,E-mail为Chaoyi0331@163.com。通信作者高枫,硕士,教授,硕士研究生导师,研究方向为神经生物学,E-mail为Yadxgf@163.com。 |
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| 中文摘要: |
| 目的探究桔皮素(TAN)对脊髓损伤(SCI)大鼠神经功能恢复的机制。 方法将60只SD大鼠随机均分为假手术(Sham)组、SCI组、SCI+TAN组、阴性对照拮抗剂(NC-antagomir)组和大鼠miR-9a-5p拮抗剂(rno-miR-9a-5p-antagomir)组。各组大鼠均干预21天。采用Basso、Beattie和Bresnahan(BBB)评分评价各组大鼠运动功能；HE、Nissl和TUNEL染色观察各组大鼠脊髓组织损伤、存活神经元数量和细胞凋亡情况；采用试剂盒检测脊髓组织炎症因子及氧化应激指标水平。采用qRT-PCR检测脊髓组织中rno-miR-9a-5p以及发状分裂相关增强子1(Hes1)和Notch2 mRNA水平；采用Western blotting检测脊髓组织B细胞淋巴瘤-2(Bcl-2)、Bcl-2相关X蛋白(Bax)、Nestin、神经元特异性烯醇化酶(NSE)、Hes1、Notch2蛋白表达水平；采用免疫组化法检测脊髓组织溴脱氧尿苷(BrdU)、Nestin、NSE蛋白表达水平。结果TAN干预后,SCI大鼠的脊髓形态明显改善,脊髓神经元数量增多,BBB评分升高,脊髓组织中TUNEL阳性细胞比例降低,炎症和氧化应激被抑制,Bax、Hes1和Notch2水平降低,Bcl-2、BrdU、Nestin、NSE和rno-miR-9a-5p水平升高。rno-miR-9a-5p-antagomir干预显著削弱了TAN的神经保护作用。 结论桔皮素通过调控rno-miR-9a-5p/Notch通路介导的炎症、氧化应激、内源性神经干细胞增殖和神经元定向分化,从而缓解大鼠SCI并促进神经功能恢复。 |
| 英文摘要: |
| AimTo investigate the mechanism of tangeretin (TAN) on nerve function recovery in rats with spinal cord injury (SCI). MethodsTotally 60 SD rats were randomly and equally divided into the sham group (Sham), SCI group, SCI+TAN group, negative control antagomir (NC-antagomir) group, and rat miR-9a-5p antagomir (rno-miR-9a-5p-antagomir) group. Rats in each group were treated for 21 days. The motor function of the rats in each group was assessed using the Basso, Beattie, and Bresnahan (BBB) scale. HE, Nissl, and TUNEL staining were used to observe spinal cord tissue damage, the number of surviving neurons, and cell apoptosis in each group. The levels of inflammatory factors and oxidative stress indicators in the spinal cord tissue were measured by using kits. The levels of rno-miR-9a-5p, hairy and enhancer of split 1 (Hes1), and Notch2 mRNA in the spinal cord tissue were detected by qRT-PCR. The protein expression levels of B-cell lymphoma-2 (Bcl-2), Bcl-2-associated X protein (Bax), Nestin, neuron-specific enolase (NSE), Hes1, and Notch2 in the spinal cord tissue were measured by Western blotting. The expression levels of bromodeoxyUridine (BrdU), Nestin, and NSE proteins in the spinal cord tissue were examined by immunohistochemical staining. ResultsAfter TAN intervention, the spinal cord morphology of SCI rats significantly improved, with an increase in the number of spinal cord neurons, elevated BBB scores, a reduction in the proportion of TUNEL-positive cells in spinal cord tissue, and suppression of inflammation and oxidative stress. The levels of Bax, Hes1, and Notch2 were decreased, while the levels of Bcl-2, BrdU, Nestin, NSE, and rno-miR-9a-5p were increased. rno-miR-9a-5p-antagomir intervention significantly attenuated the neuroprotective effects of TAN. ConclusionTAN alleviates SCI in rats and promotes neurological function recovery by regulating the rno-miR-9a-5p/Notch pathway mediated inflammation, oxidative stress, endogenous neural stem cell proliferation, and neuronal directed differentiation. |
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