万氏清心化痰汤对脑小血管病大鼠神经血管单元及AMPK/SIRT1/PGC1α通路的影响OA

Objective To investigate the therapeutic effect and mechanism of Wan's Qingxin Huatan Decoction in rats with cerebral small vessel disease(CSVD).Methods The CSVD model was established by a high-fat diet combined with a modified two-vessel occlusion(2-VO)method.Successfully modeled rats were randomly divided into a model group,low-,medium-,and high-dose Wan's Qingxin Huatan Decoction groups,and a nimodipine group,with a sham operation group also established(n=12 per group).After the respective interventions,cognitive function was assessed using the Morris water maze test(escape latency,number of platform crossings,and time spent in the target quadrant).Histopathological changes in the hippocampus were observed by hematoxylin-eosin(HE)staining.Nissl staining was used to evaluate the morphology,number,and distribution of Nissl bodies in hippocampal neurons.Golgi staining was performed to observe dendrites changes in hippocampal neurons.Western Blot analysis was conducted to detect the expression of neurovascular unit-related proteins[glial fibrillary acidic protein(GFAP),aquaporin-4(AQP-4),neuronal nuclei antigen(NeuN),and microtubule-associated protein 2(MAP-2)],as well as proteins involved in the AMP-activated protein kinase(AMPK)/sirtuin 1(SIRT1)/peroxisome proliferator-activated receptor gamma coactivator 1-alpha(PGC1α)pathway.Results Compared with the sham operation group,the model group exhibited sparsely arranged and irregularly shaped neurons in the hippocampus,a reduced number of Nissl bodies,prolonged escape latency,and increased relative protein expression of GFAP and AQP-4 in brain tissue(P＜0.05),while the number of platform crossings,time spent in the target quadrant,total dendritic length,dendritic spine density,and relative protein expression of NeuN,MAP-2,p-AMPK/AMPK,SIRT1,and PGC1α were significantly decreased(P＜0.05).Compared with the model group,the low-,medium-,and high-dose Wan's Qingxin Huatan Decoction groups and the nimodipine group showed more regularly arranged neurons,improved morphological structure,an increased number of Nissl bodies,shortened escape latency,and decreased relative protein expression of GFAP and AQP-4,along with increases in the number of platform crossings,time spent in the target quadrant,total dendritic length,dendritic spine density,and the relative protein expression of NeuN,MAP-2,p-AMPK/AMPK,SIRT1,and PGC1α(P＜0.05).No statistically significant differences were observed in any of these indicators between the high-dose Wan's Qingxin Huatan Decoction group and the nimodipine group(P＞0.05).Conclusion Wan's Qingxin Huatan Decoction can activate the AMPK/SIRT1/PGC1α pathway,repair the neurovascular unit,protect brain function and structure,and ameliorate cognitive impairment in rats with CSVD.