益气活血中药组分对慢性脑缺血小鼠认知功能及β-淀粉样蛋白与受体RAGE/LRP-1表达的影响OA

Objective To observe the effects of qi-replenishing and blood-activating traditional Chinese medicine(TCM)components(including total ginsenosides,total Ginkgo ketone ester,and total Crocus sativus glucoside)on learning and memory ability,brain histopathology,alongside amyloidβ-protein and related receptor RAGE/LRP-1 expression in chronic cerebral ischemia model mice.Methods Sixty-four SPF grade C57BL/6J mice were divided into a sham operation group,a model group,an aspirin group,and a TCM group using the random number table method,with 16 mice in each group.A chronic cerebral ischemia model was established by stimulating the bilateral common carotid arteries of C57BL/6J mice using temperature-controlled current.After successful modelling,the sham operation group and the model group were administered distilled water of the same volume as body weight by gavage.The aspirin group was administered aspirin 10 mg/(kg·d)by gavage.The TCM group was administered the TCM components 33 mg/(kg·d)by gavage.After 8 weeks of medication,learning and memory were assessed by the Morris water maze.Brain tissue pathological changes were observed via hematoxylin-eosin(HE)staining.Amyloid plaque deposition in the hippocampal CA1 region was observed via Congo red staining.Amyloid protein(Aβ1-42),the receptor of advanced glycation end products(RAGE),and low-density lipoprotein-related protein 1(LRP-1)expression were detected by Western blot,while relevant mRNA expression was detected by real-time quantitative PCR(RT-qPCR).Results Compared with the sham-operated group,the model group significantly reduced original platform crossing numbers,along with shorter swimming time and distance traveled in the original platform quadrant.Furthermore,the model group showed significantly upregulated mRNA and protein expression levels of Aβ1-42 and RAGE in brain tissues,alongside downregulated LRP-1 protein and mRNA expression(P<0.05,P<0.01).Hematoxylin-eosin staining revealed a decreased neuron quantity in the hippocampal CA1 region,cell shrinkage,indistinct nuclear membrane boundaries,and a small amount of unevenly stained amyloid plaque deposition.In comparison to the model group,these changes,except for escape latency,were significantly reversed in both the aspirin group and the TCM group,while these brain tissue pathological changes were more significant in the TCM group(P<0.05,P<0.01).Conclusion The qi-replenishing and blood-activating TCM components can improve brain tissue pathological changes in the mice model,regulate LRP-1 and RAGE expression,and reduce abnormal Aβ1-42 deposition,thereby improving the cognitive impairment caused by chronic cerebral ischemia.