中医药学报2025，Vol.53Issue(9)：17-25,9.DOI:10.19664/j.cnki.1002-2392.250181
基于神经血管单元探讨填髓通络方对脑小血管病大鼠模型认知功能的影响及神经保护作用
Study on the Effects of Tiansui Tongluo Formula on Cognitive Function and Neuroprotective Mechanism in a Rat Model of Cerebral Small Vessel Disease Based on the Neurovascular Unit
摘要
Abstract
Objective:To observe the effects of Tiansui Tongluo Formula on cognitive function,brain tissue structure,and neurovascular unit(NVU)regulation in a rat model of cerebral small vessel disease,and explore the potential therapeutic mechanisms.Methods:Seventy-five 8-week-old male SD rats were randomly divided into groups.Seven rats underwent a sham surgery(bilateral common carotid arteries were isolated but not ligated)and served as the sham operation group.The remaining rats underwent permanent bilateral common carotid artery ligation to create a model of cerebral small vessel disease.After successful modeling,the 35 rats were randomly assigned to the model group,nimodipine group,and three Tiansui Tongluo Formula groups(low,medium,high doses),with 7 rats in each group.The Tiansui Tongluo Formula groups were treated by gavage with doses of 7.2 g·kg-1·d-1,14.4 g·kg-1·d-1,and 28.8 g·kg-1·d-1,respectively.The nimodipine group was gavaged with 6.25 mg·kg-1·d-1.The sham and model groups were gavaged with an equal volume of saline.Treatment continued for 30 days.Cognitive function was assessed by the Morris water maze experiment.Brain tissue pathology was evaluated by HE staining.Immunohistochemistry was used to assess the expression of NeuN,GFAP,and Iba1 positive cells.Western blotting was used to detect the protein expression of SYN,Caspase-3,VEGF,Iba1,MBP,Cx43,and GFAP.Results:In the Morris water maze experiment,compared to the sham operation group,the model group showed a significant increase in the escape latency during the navigation trial(P<0.01)and a significant decrease in the number of platform crossings and the proportion of time spent in the platform quadrant during the spatial exploration trial(P<0.01).Compared to the model group,all does groups showed a significant reduction in escape latency(P<0.01)and a significant increase in the number of platform crossings and the proportion of time spent in the platform quadrant(P<0.01).HE staining showed that compared to the sham operation group,the model group had significantly reduced neuronal numbers,vacuolar degeneration,cell shrinkage,and hyperchromasia.The hippocampal CA1 region showed disordered cell distribution,a decrease in cell numbers,and sparse nerve fibers.Compared to the model group,the cortical and hippocampal lesions in all does groups were alleviated to varying degrees.Immunohistochemical staining showed that compared to the sham operation group,the model group had fewer NeuN-positive cells and more GFAP and Iba1-positive cells.In contrast,all does groups showed varying degrees of improvement in neuronal damage and inhibition of glial and microglial cell activation.Western blotting showed that compared to the sham operation group,the model group had significantly reduced expression of SYN,VEGF,and MBP(P<0.01),and elevated expression of Caspase-3,GFAP,Iba1,and Cx43(P<0.01).Compared to the model group,all does groups showed protein expression levels of SYN,VEGF,MBP,Caspase-3,GFAP,Iba1,and Cx43.Conclusion:Tiansui Tongluo Formula can improve cognitive function in rats with cerebral small vessel disease,increase the expression of SYN,VEGF,and MBP proteins,inhibit the expression of Caspase-3,GFAP,Iba1,and Cx43 proteins,promote synaptic plasticity,inhibit cell apoptosis,and influence brain tissue pathological changes.Its mechanisms may involve the protection of neurovascular unit(NVU)function.关键词
脑小血管病/神经血管单元/填髓通络方/认知功能Key words
Cerebral small vessel disease/Neurovascular unit/Tiansui Tongluo Formula/Cognitive function分类
医药卫生引用本文复制引用
尚鹏绘,王梦梦,高英贺,关东升,刘雨旋,王靖,任翼菡..基于神经血管单元探讨填髓通络方对脑小血管病大鼠模型认知功能的影响及神经保护作用[J].中医药学报,2025,53(9):17-25,9.基金项目
河南省重点研发与推广专项(232102310444) （232102310444）
河南省高等学校重点科研项目(23A360021) （23A360021）
