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

作　　者：周雨慧 马凯 管佳畅 彭孟凡 李晓宁 ZHOU Yuhui;MA Kai;GUAN Jiachang;PENG Mengfan;LI Xiaoning(Tangshan Hospital of Traditional Chinese Medicine,Tangshan 063000,China;HebeiUniversity of Chinese Medicine,Shijiazhuang 050200,China;The Fourth Hospital of Hebei Medical University,Shijiazhuang 050010,China;Huanghuai University,Zhumadian 463003,China)

机构地区：[1]唐山市中医医院,河北唐山063000 [2]河北中医药大学,河北石家庄050200 [3]河北医科大学第四医院,河北石家庄050010 [4]黄淮学院,河南驻马店463003

出　　处：《河北中医药学报》2025年第2期1-7,共7页Journal of Hebei Traditional Chinese Medicine and Pharmacology

基　　金：河北省中医药管理局科研计划项目(2023195);河南省科技攻关项目(242102310523)。

摘　　要：目的:研究地黄饮子(Dihuang Yinzi,DHYZ)通过抑制p38丝裂原活化蛋白激酶(p38 MAPK)通路调节血管性痴呆(vascular dementia,VD)大鼠一氧化氮(NO)合成和一氧化氮合成酶(NOS)亚型表达,发挥抗氧化应激作用的机制研究。方法:60只SD雄性大鼠随机分为假手术组、模型组、尼莫地平组、DHYZ高、中、低剂量组。采用两血管阻断法制备VD大鼠模型,卒中指数及神经症状评分筛选成模大鼠。各用药干预组给予对应药物连续灌胃30 d后进行各项检测:Morris水迷宫检测大鼠认知水平;尼氏染色法观察皮质病理变化;生化法检测脑组织NO含量、血清丙二醛(MDA)含量及血清总超氧化物歧化酶(T-SOD)活力;ELISA法检测脑组织神经型一氧化氮合成酶(nNOS)、诱导型一氧化氮合成酶(iNOS)、内皮型一氧化氮合成酶(eNOS)、活性氧(ROS)的含量;Western blot法检测脑组织p38 MAPK、iNOS蛋白的表达情况。结果:与假手术组比较,模型组大鼠卒中指数评分和神经症状评分升高、游泳总路程增多(P<0.05),逃逸平台进入次数和逃逸平台滞留时间减少(P<0.05),脑皮质神经元轮廓模糊,可见空泡样改变与胞核固缩等病理改变,尼氏小体明显减少,脑组织NO、nNOS、iNOS、ROS及血清MDA的含量均升高(P<0.05),脑组织eNOS含量、血清T-SOD的活力均下降(P<0.05),脑组织p38 MAPK、iNOS的蛋白表达均升高(P<0.05);与模型组比较,各给药组大鼠卒中指数评分和神经症状评分均下降(P<0.05),游泳总路程均减少(P<0.05),逃逸平台进入次数和逃逸平台滞留时间均增多(P<0.05),脑皮质尼氏小体脱失减轻,神经元存活增多,着色较均匀,脑组织NO、nNOS、iNOS、ROS及血清MDA的含量均降低(P<0.05),脑组织eNOS的含量、血清T-SOD的活力均升高(P<0.05),脑组织p38 MAPK、iNOS的蛋白表达均降低(P<0.05)。结论:DHYZ能够改善VD大鼠的认知功能障碍,可能是通过抑制p38 MAPK通路、减少NO过量生成和调节NOS亚型表达�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 neurological 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 observe the pathological changes of the cerebral cortex;biochemical methods to detect the content of nitric oxide(NO)in the brain tissue,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 iNOS proteins in the brain tissue.Results:Compared with the sham operation group,in the model group,the stroke index score and neurological 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 decreased;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

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 

分 类 号：R285.5[医药卫生—中药学]