摘要
目的研究芍药苷对脂多糖(LPS)诱导的急性脑损伤炎症反应及氧化应激的抑制作用及对磷脂酰肌醇3-激酶/蛋白激酶B(PI3K/Akt)通路的影响。方法将ICR小鼠(n=60)随机分为对照组(n=20)、模型组(n=20)及实验组(n=20)。实验组小鼠腹腔注射芍药苷30 mg·kg^-1·d^-1,对照组及模型组腹腔注射等量生理盐水,连续干预7 d,模型组及实验组于第7天干预1 h后腹腔注射5 mg·kg^-1 LPS构建急性脑损伤模型。建模6 h后,以苏木精-伊红(HE)染色观察小鼠海马组织病理损伤;以酶联免疫吸附(ELISA)法及比色法分别检测海马组织炎性因子及氧化应激因子含量;用蛋白质印迹法(WB)检测海马组织PI3K/Akt通路相关蛋白表达情况。结果对照组、模型组及实验组小鼠脑组织磷酸化Akt(p-Akt)蛋白相对表达量分别为0.33±0.03,0.14±0.01,0.59±0.04;PI3K蛋白相对表达量分别为0.46±0.06,0.68±0.08,0.41±0.05。模型组脑组织白细胞介素-1β(IL^-1β)、肿瘤坏死因子-α(TNF-α)、丙二醛(MDA)含量及PI3K蛋白相对表达量较对照组升高,且实验组较模型组降低(均P<0.05);模型组脑组织超氧化物歧化酶(SOD)含量及p-Akt蛋白相对表达量较对照组降低,且实验组高于模型组(均P<0.05)。结论芍药苷可有效抑制LPS急性脑损伤小鼠炎性反应及氧化应激损伤,其作用机制可能与上调PI3K/Akt通路中p-Akt蛋白表达,下调PI3K蛋白表达相关。
Objective To explore the inhibition effect of paeoniflorin on inflammation and oxidative stress of acute brain injury mice induced by lipopolysaccharide(LPS)and the influence on phosphatidylinositol 3-kinase/protein kinase B(PI3 K/Akt)pathway.Methods ICR mice(n=60)were randomly divided into control group(n=20),model group(n=20),and test group(n=20).Mice in test group were intraperitoneal injected with paeoniflorin(30 mg·kg^-1·d^-1),mice in control group and model group were intraperitoneal injected with equal amount of normal saline,intervened for 7 d,model group and test group were intraperitoneal injected with 5 mg·kg^-1 LPS to built acute brain injury mice model at 1 h after intervened on 7th d.The hippocampus pathological injury of mice was observed by hematoxylin and eosin(HE)staining at 6 h after modeling;the inflammatory cytokines and oxidative stress factors contents were detected by enzyme-linked immunosorbent assay and colorimetry;the expression of hippocampus PI3 K/Akt pathway related protein was detected by Western blot.Results The phosphorylation Akt(p-Akt)protein relative expression in mice hippocampus of control group,model group,test group were 0.33±0.03,0.14±0.01,0.59±0.04;the PI3 K protein relative expression were 0.46±0.06,0.68±0.08,0.41±0.05.The brain tissue interleukin-1β(IL^-1β),tumor necrosis factor-α(TNF-α),malondialdehyde(MDA)content and PI3 K protein relative expression in model group were higher than those in control group and test group were lower than model group(all P<0.05);the brain tissue superoxide dismutase(SOD)content and p-Akt protein relative expression in model group were lower than those in control group,and test group was higher than model group(all P<0.05).Conclusion Paeoniflorin can inhibit the inflammation and oxidative stress injury of acute brain injury mice induced by LPS effectively,the action mechanism maybe related to the up-regulation of p-Akt protein,and the down-regulation of PI3 K protein.
作者
王地梅
杨正宏
朱利君
王鸿
WANG Di-mei;YANG Zheng-hong;ZHU Li-jun;WANG Hong(Department of Emergency,Chongqing Dongnan Hospital,Chongqing 401336,China;Department of Trauma,Chongqing Dongnan Hospital,Chongqing 401336,China;Department of Critical Medicine,Chongqing Dongnan Hospital,Chongqing 401336,China)
出处
《中国临床药理学杂志》
CAS
CSCD
北大核心
2020年第17期2661-2663,共3页
The Chinese Journal of Clinical Pharmacology
