新葛根芩连汤调控BDNF/TrkB信号通路和抑制铁死亡防治阿尔茨海默病的研究OA

Objective It is to explore the intervention effect of new Gegen Qinlian Decoction(NGQD)on Alzheimer's disease(AD)via regulating brain-derived neurotrophic factor(BDNF)and tyrosine kinase B(TrkB)and inhibiting fer-roptosis.Methods Ninty male SD rats of SPF grade were taken,10 of which were randomly selected as blank group,and the other 80 rats were prepared by by chronic aluminum overload mode to establish AD models.60 AD rats screened by open field test were randomly divided into 5 groups.The high-dose,medium-dose,and low-dose groups of NGQD were giv-en NGQD 725 mg/mL,363 mg/mL,and 183 mg/mL by gavage,respectively,the donepezil group was given donepezil 0.5 mg/kg by gavage,the blank and model groups were given an equal volume of pure water by gavage,all administered once daily.After 5 weeks of continuous administration,the learning and memory abilities of the rats were assessed by Mor-ris water maze test,the pathological morphology of neurons in hippocampal CA1,CA3,and DG regions were observed by Nissl staining,the contents of β-amyloid 1-42(Aβ1-42)and Fe2+in serum,and the content of Aβ1-42 in hippocampal tissue were measured by ELISA,the content of Fe2+in hippocampal tissue was measured by a tissue iron assay kit,the protein expressions of 5-lipoxygenase(5-LOX)in hippocampal CA1,CA3,and DG regions were detected by Immunohistochemis-try,and the protein expressions of BDNF and p-TrkB in hippocampal tissue were detected by Western blot analysis.Re-sults Compared with the blank group,the escape latency of rats in the model group was significantly prolonged(P<0.05),the number of times of platform crossings was significantly decreased(P<0.05);the neuron counts in hippocam-pal CA1,CA3,and DG regions were significantly reduced(all P<0.05);the contents of Aβ1-42 and Fe2+in serum and hippocampal tissue were significantly increased(all P<0.05);the mean optical density values of protein expressions of 5-LOX in hippocampal CA1,CA3,and DG regions were significantly increased(all P<0.05);the relative protein expres-sions of BDNF and p-TrkB in hippocampal tissue were significantly reduced(all P<0.05).Compared with the model group,the escape latencies of rats in the medicated groups were significantly shortened(all P<0.05),the mean optical density values of protein expressions of 5-LOX in hippocampal CA1,CA3,and DG regions were significantly reduced(all P<0.05),while the relative protein expressions of BDNF in hippocampal tissue were significantly increased(all P<0.05);the platform crossing times of rats in the high-dose group of NGQD and donepezil group were significantly increased(all P<0.05);the neuronal counts in hippocampal CA1,CA3,and DG regions of rats in the high-dose,medium dose group of NGQD and donepezil group were significantly increased(all P<0.05),the contents of Aβ1-42 and Fe2+in serum and hippocampal tissue were significantly decreased(all P<0.05),and the relative protein expression of p-TrkB in hipp-ocampal tissue was significantly increased(P<0.05).Conclusion NGQD can improve the learning and memory abilities of AD rats via regulating BDNF/TrkB signal pathway and inhibiting ferroptosis.