摘要
为探究小白菊内酯(parthenolide,PTO)对抑郁症模型大鼠炎症反应和氧化应激的调控作用,采用探针捣毁嗅球与负压吸引联合法建立大鼠抑郁症模型,设健康组,OB模型组,OB+PTO低、中、高剂量组和OB+FLU组(阳性对照组),加药组给予腹腔注射PTO(125、250和500μg/kg)1周。ELISA检测炎症及氧化应激相关因子表达水平;免疫组化检测细胞间黏附分子1(intercellular adhesion molecule-1,ICAM-1)的表达水平;Western blotting检测组织炎症及氧化应激分子表达水平。结果显示:大鼠抑郁症模型复制成功;OB模型组大鼠血清中抑炎因子及超氧化物歧化酶(superoxide dismutase,SOD)较健康组显著下调,而促炎因子显著升高(P<0.01);OB+PTO中、高剂量组和OB+FLU组大鼠血清中抑炎因子及SOD较OB模型组升高,而促炎因子降低(P<0.05);AMP依赖的蛋白激酶α1(AMP-actived protein kinaseα1,AMPKα1)、过氧化物酶体增殖物受体γ共激活因子1α(peroxisome proliferator-activated receptor gamma co-activator-1 alpha,PGC-α1)和转运载体4(glucose transporter 4,GLUT4)的表达水平在OB+PTO中、高剂量组和OB+FLU组中得到有效恢复(P<0.05)。综上,PTO在500μg/kg剂量下对大鼠无明显毒性,并可以降低AMPKα1、PGC-α1和GLUT4的表达,抑制抑郁症大鼠体内炎症反应和氧化应激作用。
To investigate the regulatory effect of parthenolide(PTO) on inflammatory response and oxidative stress in depression rats model, we established the depression model of rats by smashing olfactory bulb(OB) with probe and negative pressure aspiration. The healthy group, OB model group, OB+PTO low(125 μg/kg), medium(250 μg/kg) and high(500 μg/kg) dose groups and OB+FLU group(positive control group) were set up. PTO was intraperitoneally injected into animals of the drug-adding groups for one week. The expression levels of inflammatory and oxidative stress related factors were detected by ELISA, intercellular adhesion molecule1(ICAM-1) was detected by immunohistochemistry, and inflammation and oxidative stress molecules were measured by Western blotting. We found that the model of depression was successfully established. Compared with healthy group,the levels of anti-inflammatory and superoxide dismutase(SOD) in serum of OB model group were significantly lower, while the levels of inflammatory factors were significantly higher(P<0.01);the levels of anti-inflammatory and SOD in serum of the OB+PTO medium, high dose groups and the OB+FLU group were higher than those of the OB model group, while the levels of inflammatory factors were lower(P<0.05);the levels of AMP-actived protein kinase α1(AMPKα1), peroxisome proliferator-activated receptor gamma co-activator-1 alpha(PGC-α1) and glucose transporter 4(GLUT4) were effectively restored in the OB+PTO medium, high dose groups and the OB+FLU group(P<0.05). In conclusion, PTO has no obvious toxicity to rats at the dosage of 500 μg/kg, and can reduce the expression of AMPKα1, PGC-α1 and GLUT4, inhibit the levels of inflammatory response and oxidative stress in rats with depression.
作者
韩亚琼
李涛
谷争
陈永新
HAN Ya-qiong;LI Tao;GU Zheng;CHEN Yong-xin(The Second Affiliated Hospital of Xinxiang Medical University,Xinxiang453002,China)
出处
《现代免疫学》
CAS
CSCD
北大核心
2020年第6期482-487,共6页
Current Immunology
基金
2017年河南省医学科技攻关计划(201702131)。
