河北中医药学报2025，Vol.40Issue(2)：1-7,7.
地黄饮子调节氧化应激改善血管性痴呆大鼠认知功能的机制研究
Mechanism of Dihuang Yinzi in Regulating Oxidative Stress and Improving Cognitive Function in Rats with Vascular Dementia
摘要
Abstract
Objective:To study the mechanism by which Dihuang Yinzi(DHYZ)regulates the synthesis of nitric oxide(NO)and the expression of nitric oxide synthase(NOS)subtypes in rats with vascular dementia(VD),and exerts the effect of anti-oxidative stress through inhibiting the p38 mitogen-activated protein kinase(p38 MAPK)pathway.Methods:Sixty male SD rats were randomly divided into a sham operation group,a model group,a nimodipine group,and high-,medium-,and low-dose DHYZ groups.A VD rat model was established by the two-vessel occlusion method,and the modeled rats were screened according to the stroke index and neuro-logical symptom scores.After the rats in each drug intervention group were given the corresponding drugs by gavage continuously for 30 days,the following tests were carried out:the Morris water maze was used to detect the cognitive level of the rats;Nissl staining to ob-serve the pathological changes of the cerebral cortex;biochemical methods to detect the content of nitric oxide(NO)in the brain tis-sue,the content of malondialdehyde(MDA)in the serum,and the activity of total superoxide dismutase(T-SOD);ELISA to detect the contents of neuronal nitric oxide synthase(nNOS),inducible nitric oxide synthase(iNOS),endothelial nitric oxide synthase(eNOS),and reactive oxygen species(ROS)in the brain tissue;and Western blotting to detect the expressions of p38 MAPK and iN-OS proteins in the brain tissue.Results:Compared with the sham operation group,in the model group,the stroke index score and neu-rological symptom score of rats increased,the total swimming distance increased(P<0.05),The number of entries into the escape platform and the retention time on the escape platform decreased(P<0.05);The outline of neurons in the cerebral cortex was blurred,and pathological changes such as vacuolar changes and nuclear pyknosis were observed;the number of Nissl bodies significantly de-creased;The NO,nNOS,iNOS,ROS in the brain tissue and MDA in the serum all increased(P<0.05),while the content of eNOS in the brain tissue and the T-SOD activity in the serum both decreased(P<0.05),and the protein expressions of p38 MAPK and iNOS both increased(P<0.05).Compared with the model group,in each drug administration group,the stroke index score and neurological symptom score of rats decreased(P<0.05),the total swimming distance decreased(P<0.05),the number of entries into the escape platform and the retention time on the escape platform increased(P<0.05);The loss of Nissl bodies in the cerebral cortex was allevia-ted,the number of surviving neurons increased,and the staining was more uniform;The NO,nNOS,iNOS,ROS and MDA all de-creased(P<0.05),while the eNOS and the activity of T-SOD increased(P<0.05),and the protein expressions of p38 MAPK and iNOS both decreased(P<0.05).Conclusion:DHYZ can improve the cognitive dysfunction in VD rats.It may exert a protective effect by inhibiting the p38 MAPK pathway,reducing the excessive production of NO,regulating the expression of NOS subtypes,and thus inhibiting oxidative stress.关键词
地黄饮子/血管性痴呆/氧化应激/p38 MAPK/一氧化氮/一氧化氮合成酶Key words
Dihuang Yinzi/VD/OS/p38 MAPK/NO/NOS分类
医药卫生引用本文复制引用
周雨慧,马凯,管佳畅,彭孟凡,李晓宁..地黄饮子调节氧化应激改善血管性痴呆大鼠认知功能的机制研究[J].河北中医药学报,2025,40(2):1-7,7.基金项目
河北省中医药管理局科研计划项目(2023195) （2023195）
河南省科技攻关项目(242102310523) （242102310523）
