龙生蛭胶囊对血管性痴呆模型大鼠学习记忆能力的影响及代谢组学研究
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篇名: 龙生蛭胶囊对血管性痴呆模型大鼠学习记忆能力的影响及代谢组学研究
TITLE: Effects of Longshengzhi capsule on learning and memory ability of vascular dementia model rats and study on its metabolomics
摘要: 目的 研究龙生蛭胶囊对血管性痴呆模型大鼠学习和记忆能力的影响,并基于代谢组学探讨其可能的作用机制。方法90只SD大鼠随机分为假手术组、模型组、甲磺酸双氢麦角毒碱片组(阳性对照,0.54mg/kg)和龙生蛭胶囊高、中、低剂量组(2.16、1.08、0.54g/kg),每组15只大鼠。除假手术组外(只穿线不结扎),各组大鼠采用双侧颈总动脉永久结扎方法制备血管性痴呆模型,并连续灌胃给药28d。采用Morris水迷宫实验测定大鼠的学习和记忆能力,采用苏木素-伊红(HE)染色观察大鼠脑海马区组织病理变化,检测大鼠血清超氧化物歧化酶(SOD)、丙二醛(MDA)、谷胱甘肽过氧化物酶(GSH-Px)水平的变化。采用超高效液相色谱-四极杆-飞行时间串联质谱(UPLC-Q-TOF/MS)技术分析血清代谢图谱,以多元统计分析方法筛选出差异代谢物,并进行代谢通路富集分析。结果Morris水迷宫实验结果显示,与模型组比较,各给药组大鼠的逃避潜伏期显著缩短、穿越平台次数显著增加、在目标象限停留时间显著延长(P<0.01或P<0.05)。血清生化指标检测结果显示,与模型组比较,甲磺酸双氢麦角毒碱片组和龙生蛭胶囊高剂量组大鼠血清SOD水平显著升高,各给药组大鼠血清GSH-Px水平显著升高、MDA水平显著降低(P<0.05或P<0.01)。HE染色结果显示,龙生蛭胶囊能够改善血管性痴呆模型大鼠脑海马区组织病理损伤。通过UPLC-Q/TOF-MS技术分析结果和正交偏最小二乘判别分析模型,共筛选鉴定出14种差异代谢物(变量投影重要性>1且P<0.05)。代谢通路富集分析结果显示,大鼠血管性痴呆涉及的代谢通路主要有维生素B6代谢、脂肪酸代谢和类固醇激素生物合成。结论龙生蛭胶囊对血管性痴呆所致大鼠学习和记忆能力下降具有一定的改善作用,其作用可能与改善血管性痴呆发生过程中脂质堆积造成的氧化应激损伤有关,涉及的代谢通路主要有维生素B6代谢、脂肪酸代谢和类固醇激素生物合成。
ABSTRACT: OBJECTIVE To study the effect of Longsheng zhi capsule on lear ning and memory ability of vascular dementia model rats and explore its mechanism based on metabonomics. METHODS Totally 90 SD rats were randomly divided into sham operation group ,model group ,Dihydroergotoxin mesylate tablet group (positive control ,0.54 mg/kg),Longshengzhi capsule high-dose,medium-dose and low-dose groups (2.16,1.08 and 0.54 g/kg),with 15 rats in each group. In addition to sham operation group (only threading without ligation ),the vascular dementia model was prepared by permanent ligation of bilateral common carotid arteries in each group ,which was administered by gavage for 28 d. Morris water maze test was used to determine the learning and memory ability of rats ;hematoxylin eosin (HE)staining was used to observe the histopathological changes of hippocampus;the serum levels of superoxide dismutase (SOD),malondialdehyde(MDA)and glutathione peroxidase (GSH-Px) were detected ;the serum metabolic map was analyzed by ultra high performance liquid chromatography quadrupole time of flight tandem mass spectrometry (UPLC-Q-TOF/MS),the specific metabolites were screened by multivariate statistical analysis ,and the metabolic pathway was enriched and analyzed. RESULTS Morris water maze test showed that compared with model group ,the escape latency of rats in each administration group was significantly shortened ,the number of crossing the platform was significantly increased ,and the residence time in the target quadrant was significantly prolonged (P<0.01 or P< 0.05). The results of serum biochemical indexes showed that compared with model group , the s erum level of SOD increased significantly in Dihydroergotoxine mesylate tablet group and Longshengzhi capsule high-dose group ,the serum level of GSH-Px increased significantly while the MDA level decreased significantly in each administration group (P<0.05 or P<0.01). HE staining showed that Longshengzhi capsule could improve the histopathological damage of hippocampus in vascular dementia model rats. A total of 14 differential metabolites were screened and identified by UPLC-Q/TOF-MS and orthogonal partial least squares discriminant analysis model (VIP>1 and P<0.05). The results of metabolic pathway enrichment analysis showed that the metabolic pathways involved in vascular dementia in rats mainly included vitamin B 6 metabolism,fatty acid metabolism and steroid hormone biosynthesis. CONCLUSIONS Longshengzhi capsule can improve the learning and memory ability of rats caused by vascular dementia. Its effect may be related to improving the oxidative stress injury caused by lipid accumulation in the process of vascular dementia. The metabolic pathways involved mainly include vitamin B 6 metabolism,fatty acid metabolism and steroid hormone biosynthesis.
期刊: 2022年第33卷第09期
作者: 孙晓丽,张锴镔,付帮泽,郭淑贞,王伟
AUTHORS: SUN Xiaoli,ZHANG Kaibin ,FU Bangze ,GUO Shuzhen ,WANG Wei
关键字: 龙生蛭胶囊;血管性痴呆;学习能力;记忆能力;代谢组学;大鼠
KEYWORDS: Longshengzhi capsule ;vascular dementia ;learning ability ;memory abilit y;metabonomics;rat
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