多模态MRI技术评估丹参酮IIA对阿尔茨海默病大鼠类淋巴系统功能的影响

doi:10.11958/20260440

天津医药 ›› 2026, Vol. 54 ›› Issue (7): 693-698.doi: 10.11958/20260440

多模态MRI技术评估丹参酮IIA对阿尔茨海默病大鼠类淋巴系统功能的影响

韩婉婷(), 付彤, 刘林栋, 倪玲玲, 武新英()

南京医科大学附属南京医院（南京市第一医院）医学影像科（邮编210000）

收稿日期:2026-02-10 修回日期:2026-03-22 出版日期:2026-07-15 发布日期:2026-07-13
通讯作者: ^△E-mail：rebeccahxt@163.com
作者简介:韩婉婷（2000），女，硕士在读，主要从事磁共振成像方面研究。E-mail：hanwendy04@163.com
基金资助:
江苏省自然科学基金(BK20230155)

An experimental study of multimodal MRI technology for evaluating the impact of tanshinone ⅡA on glymphatic system function in rats with Alzheimer's disease

HAN Wanting(), FU Tong, LIU Lindong, NI Lingling, WU Xinying()

Department of Radiology, Nanjing First Hospital, Nanjing Medical University, Nanjing 210000, China

Received:2026-02-10 Revised:2026-03-22 Published:2026-07-15 Online:2026-07-13
Contact: ^△E-mail：rebeccahxt@163.com

韩婉婷, 付彤, 刘林栋, 倪玲玲, 武新英. 多模态MRI技术评估丹参酮IIA对阿尔茨海默病大鼠类淋巴系统功能的影响[J]. 天津医药, 2026, 54(7): 693-698.

HAN Wanting, FU Tong, LIU Lindong, NI Lingling, WU Xinying. An experimental study of multimodal MRI technology for evaluating the impact of tanshinone ⅡA on glymphatic system function in rats with Alzheimer's disease[J]. Tianjin Medical Journal, 2026, 54(7): 693-698.

摘要/Abstract

摘要：

目的采用多模态MRI技术评估丹参酮ⅡA（Tan-ⅡA）对阿尔茨海默病（AD）大鼠类淋巴系统功能的影响。方法将12只雄性SD大鼠随机分为Control组、AD模型组、AD+Tan-ⅡA组及AD+Tgn-073组，每组3只。除Control组外，其余3组均通过立体定位注射Aβ1-40构建AD模型，建模后AD+Tan-ⅡA组及AD+Tgn-073组分别给予Tan-ⅡA与AQP4激动剂Tgn-073干预4周。采用多b值扩散加权成像（DWI）分析大鼠脑组织水分子扩散特性，计算表观扩散系数（ADC）、分布扩散系数（DDC）及异质性指数α值。通过动态对比增强MRI（DCE-MRI）及免疫荧光技术分析大鼠海马、纹状体及皮质区域信号强度变化及水通道蛋白4（AQP4）表达。结果与Control组相比，AD组ADC、DDC及异质性指数α值均降低（P<0.05）。与AD组相比，经药物干预后AD+Tan-ⅡA组ADC、DDC及异质性指数α差异均无统计学意义；Tgn-073上述参数均升高（P<0.05）。DCE-MRI显示，在海马与皮质区域，AD+Tgn-073组在对比剂注射后早期（40或60 min）信号强度比高于AD组（P<0.05），AD+Tan-ⅡA组海马区域则在中后期（100、120、150 min）信号强度升高（P<0.05）。免疫荧光显示，与Control组相比，AD组大鼠仅海马区AQP4表达升高，而与AD组相比，AD+Tgn-073组及AD+Tan-ⅡA组海马和纹状体区域AQP4表达下调。结论 Tan-ⅡA可改善AD大鼠脑内类淋巴系统转运功能，其机制可能涉及非AQP4直接依赖的途径。

关键词: 阿尔茨海默病, 大鼠, 磁共振成像, 丹参酮ⅡA, 类淋巴系统

Abstract:

Objective To evaluate the effects of tanshinone ⅡA (Tan-ⅡA) on glymphatic system function in Alzheimer's disease (AD) rats using multimodal MRI techniques. Methods Twelve male SD rats were randomly divided into the control group (healthy controls), the AD model group, the AD+Tan-ⅡA group and the AD+Tgn-073 group, with 3 rats in each group. Except for the control group, all remaining three groups underwent stereotaxic injection of Aβ1-40 to establish the AD model. Following modeling, the AD+Tan-ⅡA group and the AD+Tgn-073 group received four weeks of intervention with Tan-ⅡA and the AQP4 agonist Tgn-073, respectively. Multi-b-value diffusion-weighted imaging (DWI) was used to analyze water molecule diffusion characteristics in rat brain tissue, with calculation of the apparent diffusion coefficient (ADC), distributed diffusion coefficient (DDC) and heterogeneity index α. Dynamic contrast-enhanced MRI (DCE-MRI) and immunofluorescence were employed to assess signal intensity changes and aquaporin-4 (AQP4) expression in the hippocampal, striatal and cortical regions. Results Compared with the control group, the ADC, DDC and heterogeneity index α values were significantly decreased in the AD group (all P<0.01). Compared with the AD group, there were no statistically significant differences in ADC, DDC or α values in the AD+Tan-ⅡA group after drug intervention. In contrast, all three parameters were elevated in the AD+Tgn-073 group (P<0.05). DCE-MRI revealed that in the hippocampal and cortical regions, the signal intensity ratio was higher in the AD+Tgn-073 group than that of the AD group in the early post-contrast phase (40 or 60 min, P<0.05), whereas the AD+Tan-ⅡA group showed elevated signal intensity in the cortical region during the mid-to-late phase (100, 120, and 150 min, P<0.05). Immunofluorescence demonstrated that compared with the control group, AQP4 expression was elevated exclusively in the hippocampus of AD rats. Compared with the AD group, AQP4 expression was downregulated in both hippocampal and striatal regions of the AD+Tgn-073 group and the AD+Tan-ⅡA group. Conclusion Tan-ⅡA can improve glymphatic transport function in brain of AD rats, and the underlying mechanism may involve pathways that are not directly dependent on AQP4.

Key words: Alzheimer's disease, rats, MRI, tanshinone-ⅡA, glymphatic system

中图分类号:

R445.2，R749.16

图/表 5

表1 各组大鼠脑部扩散参数（ADC，DDC，α）比较

Tab.1 Comparison of diffusion parameters（ADC，DDC and α） in brain of rats between the four groups （n=3，$\stackrel{-}{x}\pm s$）

组别	ADC/（×10^-3mm²/s）	DDC/（×10^-3mm²/s）	异质性指数α
Control组	1.11±0.03	0.83±0.10	0.84±0.02
AD组	0.61±0.04^a	0.42±0.05^a	0.64±0.03^a
AD+Tgn-073组	0.91±0.08^b	0.69±0.03^b	0.73±0.10^b
AD+Tan-ⅡA组	0.76±0.20	0.55±0.13	0.67±0.05
F	11.030^＊＊	14.120^＊＊	28.250^＊＊

图1 各组海马、纹状体和皮质的信号强度随时间变化的趋势＊＊P<0.01；海马：F组间=13.570＊＊，F时间=28.800＊＊，F交互=6.388＊＊；纹状体：F组间=1.506，F时间=12.580＊＊，F交互=0.862；皮质：F组间=10.860＊＊，F时间=13.250＊＊，F交互=5.345＊＊；a与AD组相比，P<0.05。

Fig.1 Temporal trends of signal intensity variations in hippocampus, striatum and cortex of each group

图2 各组代表性的T1加权MR平扫+增强影像比例尺代表1 cm。

Fig.2 Representative T1-weighted MR plain scan combined with contrast-enhanced images between the four groups

表2 各组大鼠海马、纹状体和皮质中AQP4表达的比较

Tab.2 Comparison of AQP4 in hippocampus，striatum and cortex of rats between the four groups （n=12，$\stackrel{-}{x}\pm s$）

组别	海马	纹状体	皮质
Control组	0.98±0.08	0.99±0.05	1.00±0.04
AD组	1.28±0.08^a	0.98±0.13	0.94±0.10
AD+Tgn-073组	1.11±0.12^b	0.81±0.07^b	0.84±0.06^b
AD+Tan-ⅡA组	1.09±0.14^b	0.88±0.04^b	0.91±0.05
F	14.790^＊＊	13.210^＊＊	10.670^＊＊

图3 各组大鼠海马、纹状体及皮质区域AQP4的表达（免疫荧光染色，×200）黄色荧光为AQP4表达，蓝色荧光为DAPI表达。

Fig.3 Expression of AQP4 in the hippocampus, striatum and caudal cortex of rats in four groups (immunofluorescence staining, ×200)

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多模态MRI技术评估丹参酮IIA对阿尔茨海默病大鼠类淋巴系统功能的影响

An experimental study of multimodal MRI technology for evaluating the impact of tanshinone ⅡA on glymphatic system function in rats with Alzheimer's disease

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