降糖药对帕金森病的影响和作用机制探讨

doi:10.16138/j.1673-6087.2025.05.10

摘要/Abstract

摘要：

帕金森病（Parkinson disease，PD）是一种慢性神经退行性疾病，其发生机制主要与神经元变性和α突触核蛋白异常聚集有关。研究表明，PD患者合并2型糖尿病的风险较高。降糖药物通过调节糖代谢、改善胰岛素敏感性等途径调控血糖，部分降糖药物还兼具神经保护或抗氧化作用，近年来其在神经退行性疾病中的作用机制研究日益深入。本文对PD的病理基础和相关发病机制进行综述，探讨降糖药物对PD病程进程的影响和作用。

关键词: 帕金森病, 糖尿病, 降糖药物

Abstract:

Parkinson disease (PD) is a chronic neurodegenerative disease, and the pathgenesis is mainly related to neuronal degeneration and abnormal accumulation of αSyn. Some studies have shown that patients with PD are more likely to suffer from type 2 diabetes mellitus. Hypoglycemic drugs regulate blood glucose through modulating glucose metabolism and improving insulin sensitivity. Some of hypoglycemic drugs also have neuroprotective or antioxidant effect, and their mechanisms of action in neurodegenerative diseases have been extensively studied in recent years. This article reviews the pathological basis and related pathogenesis of PD, exploring the effect of hypoglycemic drugs on the progression of PD.

Key words: Parkinson disease, Diabetes mellitus, Hypoglycemic agent

中图分类号:

R742

张海涵, 荆玮, 单悦童, 张玉玲, 陈安安, 龙思琪, 王宇泽, 李威, 潘卫东. 降糖药对帕金森病的影响和作用机制探讨[J]. 内科理论与实践, 2025, 20(05): 399-404.

ZHANG Haihan, JING Wei, SHAN Yuetong, ZHANG Yuling, CHEN Anan, LONG Siqi, WANG Yuze, LI Wei, PAN Weidong. Discussion on effect and mechanism of hypoglycemic drugs on Parkinson disease[J]. Journal of Internal Medicine Concepts & Practice, 2025, 20(05): 399-404.

图/表 1

表1

部分口服降糖药对PD影响的研究

降糖药	研究对象	剂量/浓度	评价参数	结论
双胍类	T2DM患者	不同暴露量和使用强度	糖尿病患者3年和5年PD发生率	接受低剂量和低强度二甲双胍患者PD发生率低^[32]
	成年雄性大鼠	每天口服500 mg/kg	大鼠脑组织中丙二醛、TNF-α水平等	二甲双胍改善糖尿病合并PD大鼠的炎性标志物^[33]
	12周龄小鼠	不同浓度范围	线粒体活性、神经元进程的长度	二甲双胍降低PD发病风险^[34]
	中老年退伍军人	不同平均日剂量	糖尿病患者使用二甲双胍2年后PD发生率	使用二甲双胍的患者PD风险更低^[35]
	荟萃分析，基于19份报告	/	基于STATA V.14.2 进行分析	二甲双胍单一疗法使PD发生率增加^[19]
	荟萃分析，纳入 10 项研究	/	基于Review Manager分析	二甲双胍会显著增加 PD风险^[36]
SGLT-2抑制剂	10周龄雄性大鼠	恩格列净每天口服 10 mg/kg和20 mg/kg	大鼠僵值杆测试、转棒测试、组织学检查	恩格列净在 PD大鼠中诱导有益的神经调节作用^[37]
SGLT-2抑制剂	40岁以上糖尿病患者	/	PD发病率	SGLT-2抑制剂与PD发病风险降低相关^[38]
DPP-4抑制剂、GLP-1激动剂	回顾性研究，纳入697例患者	/	多巴胺转运体可用性、运动并发症发生率等	DPP-4抑制剂在PD患者中减少运动并发症风险^[39]
	接受二甲双胍治疗的糖尿病患者	患者中位限定日剂量为0.32	PD发病率	糖尿病患者使用 DPP-4抑制剂和二甲双胍降低 PD发生风险^[40]
	荟萃研究，涉及15项研究	/	应用Review Manager 5.3进行分析	DPP-4抑制剂可能降低糖尿病患者患特发性 PD发生风险^[41]
	野生8周龄C57BL/6J雄鼠	艾塞那肽每天50 μg/kg，利格列汀每天5 mg/kg，小鼠颈后皮下注射	大鼠旷场测试、爬杆测试、步态分析等	艾塞那肽、利格列汀可逆转PD小鼠运动功能障碍^[42]
胰岛素增敏剂	回顾性研究，纳入62 400例糖尿病患者	/	PD年发病率	噻唑烷二酮的使用与 PD发生率呈负相关^[43]
胰岛素增敏剂	回顾性研究，纳入38 521例糖尿病患者	非TZD治疗组和TZD治疗组	PD发病率	噻唑烷二酮治疗组PD风险降低，且与使用剂量相关^[44]

表1

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