黄芪甲苷对CUMS抑郁症大鼠模型的血清代谢组学研究

Effects of astragaloside IV on serum metabolomics of CUMS depression rats

目的运用血清代谢组学的方法探索黄芪甲苷(astragaloside IV,AST)对慢性不可预见性轻度应激(chronic unpredictable mild stress,CUMS)抑郁症大鼠的影响。方法 CUMS构建抑郁症模型。大鼠随机分为5组:健康组(Ctrl);模型组(CUMS);黄芪甲苷(10、20、50 mg/kg)组。苏木素-伊红(hematoxylin-eosin,HE)染色观察脑组织病变。酶联免疫吸附实验(enzyme-linked immunosorbent assay,ELISA)检测白细胞介素(interleukin,IL)-1β、肿瘤坏死因子(tumor necrosis factorα,TNF-α)、总胆固醇(total cholesterol,TC)、甘油三酯(triglyceride,TG)、低密度脂蛋白胆固醇(low density lipoprotein cholesterin,LDL-c)、高密度脂蛋白胆固醇(high density lipoprotein cholesterin,HDL-c)、一氧化氮(nitric oxide,NO)、超氧化物歧化酶(superoxide dismutase,SOD)、丙二醛(methane dicarboxylic aldehyde,MDA)、谷胱甘肽(glutathione,GSH)水平。蛋白印记检测CPT-1、ACOX1、PPAR-α、SREBP-1c、FAS和DGAT-2表达。结果黄芪甲苷可改善CUMS抑郁症大鼠脑组织锥体细胞层较薄,细胞密度相对较少,排列紊乱、稀疏,细胞边缘模糊不清等病变。模型组大鼠IL-1β、TNF-α的水平高于健康组(P<0.01)。黄芪甲苷(10、20、50 mg/kg)组大鼠IL-1β、TNF-α的水平低于模型组(P<0.01)。黄芪甲苷可降低CUMS抑郁症大鼠血糖浓度(P<0.01)。与健康组相比,模型组大鼠TC、TG、LDL-c水平升高,HDL-c水平下降(P<0.01)。与模型组相比,黄芪甲苷(10、20、50 mg/kg)组大鼠TC、TG、LDL-c水平降低,HDL-c水平上升(P<0.01)。黄芪甲苷可减弱CUMS抑郁症大鼠CPT-1、ACOX1、PPAR-α表达,增强SREBP-1c、FAS、DGAT-2表达(P<0.01)。与健康组相比,模型组大鼠NO和MDA水平升高,SOD和GSH水平下降(P<0.01)。与模型组相比,黄芪甲苷(10、20、50 mg/kg)组大鼠NO和MDA水平降低,SOD和GSH水平上升(P<0.01)。结论黄芪甲苷可改善CUMS抑郁症大鼠脑组织病变、炎症反应、糖脂代谢异常及氧化应激。

This study aims to explore the effect of astragaloside IV （AST） on the chronic unpredictable mild stress （CUMS） depression in rats via serum metabolomies. Rats were randomly divided into 5 groups： healthy group （Ctrl）, model 20, 50 mg/kg） tissues staining; group （CUMS）, and astragaloside Ⅳ （10, groups. The pathological changes of brain were observed by hematoxylin-eosin （HE） ELISA was used to detect the levels of interleukin （IL）-1β, tumor necrosis factor α （TNF-α）, total cholesterol （TC）, triglyceride （TG）,low density lipoprotein cholesterin （LDL-c）, high density lipoprotein cholesterin （HDL-c）, nitric oxide （NO）, superoxide dismutase （SOD）, methane dicarboxylic aldehyde （MDA） and glutathione （GSH）. The expression levels of CPT-1, PPAR-α, ACOX1, SREBP-1c, FAS and DGAT-2 were measured by Western blotting. Data showed that astragaloside Ⅳ ameliorated pathological changes, including thin hippocampal pyramidal cell layer, irregularly and loosely arranged cells and so on, in brain tissues of CUMS depression rats. Furthermore, the levels of IL-1β and TNF-α in model group were higher than those of healthy group （P〈0.01）; the levels of IL-1 and TNF-ct in astragaloside IV （10, 20, 50 mg/kg） groups were lower than those of model group （P〈0.01）. The concentration of blood sugar in CUMS depression rats was decreased by astragaloside IV （P〈0.01）. Compared with healthy group, the levels of TC, TG, LDL-c in model group were increased with the decline of HDL-c （P〈0.01）. Compared with model group, the levels of TC, TG, LDL-c in astragaloside Ⅳ （10, 20, 50 mg/kg） groups were reduced, while HDL-c level elevated （P〈0.01）. The expression levels of CPT-1, PPAR-α and ACOX1 in CUMS depression rats were attenuated by astragaloside Ⅳ. While the expression of SREBP-1c, FAS and DGAT-2 in CUMS depression rats was elevated by astragaloside Ⅳ （P〈0.01）. Compared with healthy group, the levels of NO and MDA in model group were enhanced, while the levels of SOD and GSH decreased （P〈0.01）; compared with model group, the levels of NO and MDA in astragaloside Ⅳ （10, 20, 50 mg/kg） groups were reduced, wihle the levels of SOD and GSH increased （P〈 0.01）. Taken together, Astragaloside Ⅳ ameliorates brain tissues pathological changes, inflammatory reaction, abnormal glucose and lipid metabolism and oxidative stress in CUMS depression rats.