中国临床药理学与治疗学 ›› 2026, Vol. 31 ›› Issue (4): 551-560.doi: 10.12092/j.issn.1009-2501.2026.04.015
张洁妤, 翁伊娜, 曹飞(
)
收稿日期:2025-01-05
修回日期:2025-08-15
出版日期:2026-04-26
发布日期:2026-04-30
通讯作者:
曹飞
E-mail:kongzhongchenke@126.com
作者简介:张洁妤，硕士，副教授，研究方向：神经退行性疾病
基金资助:
Jieyu ZHANG, Yina WENG, Fei CAO()
Received:2025-01-05
Revised:2025-08-15
Online:2026-04-26
Published:2026-04-30
Contact:
Fei CAO
E-mail:kongzhongchenke@126.com
摘要：
帕金森病（Parkinson's disease， PD）是一种年龄相关性缓慢进行性锥体外系疾病，其患病率随我国人口老龄化进程逐年增长。由于高特异性生物标志物的缺乏，PD早期诊疗仍是一个巨大挑战。微小 RNA（microRNAs，miRNAs）是一类短链非编码RNA分子，已被发现在PD患者体液中异常表达，且通过调节内源性基因参与PD病理过程。miRNAs特异性表达谱的发现使其成为具有吸引力的非侵入性生物标志物和新型治疗靶点。本文将综述miRNAs表达异常与PD诊疗关系的相关研究，并从表达谱的变化、诊断价值、治疗潜力三个方面，阐述miRNAs在PD诊疗中的研究进展。
中图分类号:
张洁妤, 翁伊娜, 曹飞. microRNAs在帕金森病患者中表达谱的变化及诊疗潜力展望[J]. 中国临床药理学与治疗学, 2026, 31(4): 551-560.
Jieyu ZHANG, Yina WENG, Fei CAO. microRNAs expression profile changes in patients with Parkinson's disease and prospects for potential diagnosis and treatment[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2026, 31(4): 551-560.
| 作者 | 样本量 | 样本来源 | miRNAs | 相对 表达量 | |
| PD组 | 对照组 | ||||
| Martins et al.[ | 19 | 13 | PBMCs | miR-335, miR-374a/b, miR-199, miR-126, miR-151-5p, miR-29b/c, miR-147, miR-28-5p, miR-30b/c, miR-301a, miR-26a | 下降 |
| Zhuang et al.[ | 120 | 120 | 血浆、脑脊液 | miR-125b | 下降 |
| Pavelka et al.[ | 387 | 416 | 血浆 | miR-145-5p, miR-151a-3p, miR-145-3p, miR-130a-3p, miR- | 升高 |
| Li et al.[ | 53 | 60 | 血浆 | miR-10b-5p, miR-150-5p, miR-342-3p, miR-186-5p, miR-192-5p,miR-361-3p, miR-155-5p, miR- | 下降 |
| miR-4433b-5p, miR-335-3p, miR-130b-5p, miR-766-3p, miR-744-5p, miR- | 升高 | ||||
| Qiu et al.[ | 23 | 30 | 血浆 | miR-1976, miR-153, miR-103a, miR-29q | 升高 |
| miR-210, miR-375, miR-146a, miR-101a | 下降 | ||||
| Rai et al.[ | 16 | 16 | 血浆 | miR- miR-203b-5p, miR-205-5p, miR-708-3p, miR-106b-3p, miR-23b-3p, miR-203a-3p | 升高 |
| miR-143-5p, miR- | 下降 | ||||
| Chen et al.[ | 75 | 73 | 血浆 | miR-153, miR-223 | 下降 |
| Jang et al.[ | 5 | 20 | 血浆 | miR-195-5p, miR-495-3p, miR-23b-3p, miR-323a-3p, miR-30c-2-3p, miR-27a-3p | 升高 |
| Zhang et al.[ | 13 | 27 | 脑脊液 | miR-124 | 下降 |
| Tan et al.[ | 7 | 4 | 脑脊液 | miR-486-5p, miR-122-5p, miR-451a, miR-423-5p, let-7b-5p, miR-151a-3p, miR-320a, miR-574-5p, miR-206, miR-204-5p, miR- | 升高 |
| Tong et al.[ | 209 | 50 | 血清、脑脊液 | miR-151a-5p, miR-24, miR-485-5p, miR-331-5p, miR-214 | 升高 |
| miR-331-3p, miR-485-3p | 下降 | ||||
| Wu et al.[ | 50 | 50 | 血清 | miR-19b-3p | 下降 |
| Wan et al.[ | 51 | 51 | 血清 | miR-218-5p, miR-320-5p | 下降 |
| Aguilar et al.[ | 60 | 40 | 血清 | miR-26b-5p, miR-25-3p, miR-191-5p, miR-330, miR- | 升高 |
| Lin et al.[ | 92 | 64 | 血清 | miR*485-3p | 下降 |
| Soto et al.[ | 20 | 40 | 血清 | miR-22-3p, miR-16-5p, miR-19b-3p | 下降 |
| Manna et al.[ | 40 | 33 | 血清 | miR-22-3p, miR-223-5p | 升高 |
| Citterio et al.[ | 45 | 39 | 血清 | miR-7-1-5p, miR-223-3p | 升高 |
| Guévremont et al.[ | 287 | 168 | 血清 | miR-24-3p | 升高 |
| Cressatti et al.[ | 83 | 77 | 唾液 | miR-223, miR-153 | 下降 |
| Chen et al.[ | 30 | 330 | 唾液 | miR-874, miR-145-3p | 升高 |
表 1 帕金森病患者中微小 RNA（miRNAs）的异常表达
Table 1 Abnormal expression of miRNAs in patients with Parkinson's disease
| 作者 | 样本量 | 样本来源 | miRNAs | 相对 表达量 | |
| PD组 | 对照组 | ||||
| Martins et al.[ | 19 | 13 | PBMCs | miR-335, miR-374a/b, miR-199, miR-126, miR-151-5p, miR-29b/c, miR-147, miR-28-5p, miR-30b/c, miR-301a, miR-26a | 下降 |
| Zhuang et al.[ | 120 | 120 | 血浆、脑脊液 | miR-125b | 下降 |
| Pavelka et al.[ | 387 | 416 | 血浆 | miR-145-5p, miR-151a-3p, miR-145-3p, miR-130a-3p, miR- | 升高 |
| Li et al.[ | 53 | 60 | 血浆 | miR-10b-5p, miR-150-5p, miR-342-3p, miR-186-5p, miR-192-5p,miR-361-3p, miR-155-5p, miR- | 下降 |
| miR-4433b-5p, miR-335-3p, miR-130b-5p, miR-766-3p, miR-744-5p, miR- | 升高 | ||||
| Qiu et al.[ | 23 | 30 | 血浆 | miR-1976, miR-153, miR-103a, miR-29q | 升高 |
| miR-210, miR-375, miR-146a, miR-101a | 下降 | ||||
| Rai et al.[ | 16 | 16 | 血浆 | miR- miR-203b-5p, miR-205-5p, miR-708-3p, miR-106b-3p, miR-23b-3p, miR-203a-3p | 升高 |
| miR-143-5p, miR- | 下降 | ||||
| Chen et al.[ | 75 | 73 | 血浆 | miR-153, miR-223 | 下降 |
| Jang et al.[ | 5 | 20 | 血浆 | miR-195-5p, miR-495-3p, miR-23b-3p, miR-323a-3p, miR-30c-2-3p, miR-27a-3p | 升高 |
| Zhang et al.[ | 13 | 27 | 脑脊液 | miR-124 | 下降 |
| Tan et al.[ | 7 | 4 | 脑脊液 | miR-486-5p, miR-122-5p, miR-451a, miR-423-5p, let-7b-5p, miR-151a-3p, miR-320a, miR-574-5p, miR-206, miR-204-5p, miR- | 升高 |
| Tong et al.[ | 209 | 50 | 血清、脑脊液 | miR-151a-5p, miR-24, miR-485-5p, miR-331-5p, miR-214 | 升高 |
| miR-331-3p, miR-485-3p | 下降 | ||||
| Wu et al.[ | 50 | 50 | 血清 | miR-19b-3p | 下降 |
| Wan et al.[ | 51 | 51 | 血清 | miR-218-5p, miR-320-5p | 下降 |
| Aguilar et al.[ | 60 | 40 | 血清 | miR-26b-5p, miR-25-3p, miR-191-5p, miR-330, miR- | 升高 |
| Lin et al.[ | 92 | 64 | 血清 | miR*485-3p | 下降 |
| Soto et al.[ | 20 | 40 | 血清 | miR-22-3p, miR-16-5p, miR-19b-3p | 下降 |
| Manna et al.[ | 40 | 33 | 血清 | miR-22-3p, miR-223-5p | 升高 |
| Citterio et al.[ | 45 | 39 | 血清 | miR-7-1-5p, miR-223-3p | 升高 |
| Guévremont et al.[ | 287 | 168 | 血清 | miR-24-3p | 升高 |
| Cressatti et al.[ | 83 | 77 | 唾液 | miR-223, miR-153 | 下降 |
| Chen et al.[ | 30 | 330 | 唾液 | miR-874, miR-145-3p | 升高 |
| 作者 | miRNAs | 模型 | 治疗方法 | 功能 |
| Wang et al.[ | miR-205 | SH-SY5Y细胞 | miR-205模拟物 | 抑制 LRRK2表达 |
| Fan et al.[ | miR-153 | PD小鼠 | miR-153模拟物 | 抑制α-突触核蛋白表达 |
| He et al.[ | miR-137 | PD小鼠 | miR-137模拟物 | 抑制α-突触核蛋白表达 |
| Zhou et al.[ | miR-7 | PD小鼠 | miR-7模拟物 | 抑制NLRP3表达 |
| Li et al.[ | miR-30e | PD小鼠 | miR-30e模拟物 | 抑制NLRP3表达 |
| Zeng et al.[ | miR-135b | SH-SY5Y、PC-12细胞 | miR-135b模拟物 | 抑制NLRP3表达 |
| Hu et al.[ | miR-425 | PD小鼠 | miR-425模拟物 | 抑制RIPK1表达 |
| Wu et al.[ | miR-543-3p | PD小鼠 | miR-543-3p模拟物 | 抑制α-突触核蛋白表达 |
| Li et al.[ | miR-150 | BV2细胞 | miR-150模拟物 | 抑制促炎细胞因子表达 |
| Wang et al.[ | miR-29c-3p | PD小鼠 | miR-29c-3p模拟物 | 激活NFAT5 |
| He et al.[ | miR-100a-5p | MN9D细胞 | miR-100a-5p模拟物 | 激活Nox4/ROS/Nrf2信号通路 |
| Esfahani et al.[ | miR-101-3p | SH-SY5Y细胞 | miR-101-3p模拟物 | 促进PGC1α表达 |
| Yao et al.[ | miR-221 | PD小鼠 | miR-221模拟物 | 抑制Bim/Bax/caspase-3信号通路 |
| Esteves et al.[ | miR-124-3p | PD小鼠 | miR-124-3p模拟物 | 减少多巴胺能神经元死亡 |
| Almeida et al.[ | miR-134 | PD大鼠 | miR-134抑制剂 | 减弱纹状体多巴胺能神经元损伤 |
| Vallelunga et al.[ | miR-30c-5p | PD小鼠 | miR-30c-5p抑制剂 | 上调ATG5表达 |
| Lv et al.[ | miR-3473b | PD小鼠 | miR-3473b抑制剂 | 增加TREM2和ULK1的表达 |
| Dong et al.[ | miR-421 | PD小鼠 | miR-421抑制剂 | 抑制调节MEF2D的表达 |
| Kaurani et al.[ | miR-129-5p | PD小鼠 | miR-129-5p抑制剂 | 抑制谷氨酸转运蛋白表达 |
表 2 miRNAs与PD治疗
Table 2 miRNAs and treatment of Parkinson's disease
| 作者 | miRNAs | 模型 | 治疗方法 | 功能 |
| Wang et al.[ | miR-205 | SH-SY5Y细胞 | miR-205模拟物 | 抑制 LRRK2表达 |
| Fan et al.[ | miR-153 | PD小鼠 | miR-153模拟物 | 抑制α-突触核蛋白表达 |
| He et al.[ | miR-137 | PD小鼠 | miR-137模拟物 | 抑制α-突触核蛋白表达 |
| Zhou et al.[ | miR-7 | PD小鼠 | miR-7模拟物 | 抑制NLRP3表达 |
| Li et al.[ | miR-30e | PD小鼠 | miR-30e模拟物 | 抑制NLRP3表达 |
| Zeng et al.[ | miR-135b | SH-SY5Y、PC-12细胞 | miR-135b模拟物 | 抑制NLRP3表达 |
| Hu et al.[ | miR-425 | PD小鼠 | miR-425模拟物 | 抑制RIPK1表达 |
| Wu et al.[ | miR-543-3p | PD小鼠 | miR-543-3p模拟物 | 抑制α-突触核蛋白表达 |
| Li et al.[ | miR-150 | BV2细胞 | miR-150模拟物 | 抑制促炎细胞因子表达 |
| Wang et al.[ | miR-29c-3p | PD小鼠 | miR-29c-3p模拟物 | 激活NFAT5 |
| He et al.[ | miR-100a-5p | MN9D细胞 | miR-100a-5p模拟物 | 激活Nox4/ROS/Nrf2信号通路 |
| Esfahani et al.[ | miR-101-3p | SH-SY5Y细胞 | miR-101-3p模拟物 | 促进PGC1α表达 |
| Yao et al.[ | miR-221 | PD小鼠 | miR-221模拟物 | 抑制Bim/Bax/caspase-3信号通路 |
| Esteves et al.[ | miR-124-3p | PD小鼠 | miR-124-3p模拟物 | 减少多巴胺能神经元死亡 |
| Almeida et al.[ | miR-134 | PD大鼠 | miR-134抑制剂 | 减弱纹状体多巴胺能神经元损伤 |
| Vallelunga et al.[ | miR-30c-5p | PD小鼠 | miR-30c-5p抑制剂 | 上调ATG5表达 |
| Lv et al.[ | miR-3473b | PD小鼠 | miR-3473b抑制剂 | 增加TREM2和ULK1的表达 |
| Dong et al.[ | miR-421 | PD小鼠 | miR-421抑制剂 | 抑制调节MEF2D的表达 |
| Kaurani et al.[ | miR-129-5p | PD小鼠 | miR-129-5p抑制剂 | 抑制谷氨酸转运蛋白表达 |
图 1 微小 RNA 抑制剂的作用机制
Fig.1 Mechanism of action of miRNA inhibitors This figure illustrates three main strategies for inhibiting miRNA function: A: anti-miRNA Oligonucleotides (AMOs) that directly bind to and degrade mature miRNAs; B: antagomirs, which are cholesterol-conjugated AMOs for enhanced in vivo stability and delivery.
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