摘要
目的:探讨辛伐他汀对脂多糖(LPS)诱导的大鼠急性肺损伤(ALI)的保护作用及其对核因子E2相关因子2(Nrf2)/抗氧化反应元件(ARE)信号通路的调控机制。方法:SD大鼠随机分为4组:正常组、模型组、实验组、阳性对照药地塞米松干预组(DXMS),每组10只,实验组、DXMS组分别腹腔注射1 ml辛伐他汀溶液(5 mg/kg)和1 ml DXMS溶液(5 mg/kg),正常组、模型组分别腹腔注射等量生理盐水;腹腔注射30 min后,模型组、实验组、DXMS组分别尾静脉注射0.5 ml LPS(5 mg/kg)构建ALI模型,正常组尾静脉注射等量生理盐水。尾静脉注射4 h后处死大鼠。HE染色观察大鼠组织病理改变,TUNEL染色检测细胞凋亡,DCFH-DA染色检测活性氧(ROS)含量,qRT-PCR、免疫组化及Western blot检测Nrf2、HO-1表达。结果:与正常组相比,模型组大鼠肺组织细胞凋亡率、ROS含量、Nrf2和HO-1表达明显升高,ALI组织病理学变化显著;与模型组相比,实验组和DXMS组大鼠肺组织细胞凋亡率、ROS含量明显降低,Nrf2和HO-1表达明显升高,ALI组织病理症状明显改善(P<0.05)。结论:辛伐他汀可保护ALI大鼠肺组织,通过激活Nrf2/ARE通路增强Nrf2和HO-1表达、发挥抗氧化作用、抑制细胞凋亡实现。
Objective:To explore protect effect of simvastatin on lipopolysaccharide(LPS)-induced acute lung injury(ALI)in rats and its regulatory mechanism on nuclear factor E2 related factor 2(Nrf2)/antioxidant response element(ARE)signaling pathway.Methods:SD rats were randomly divided into 4 groups:normal group,model group,experimental group,and positive control drug dexamethasone intervention group(DXMS),10 cases in each group.Experimental group and DXMS group were intraperitoneally injected with 1 ml simvastatin solution(5 mg/kg)and 1 ml DXMS solution(5 mg/kg),respectively.Normal group and model group were intraperitoneally injected with same dose of normal saline.After 30 min of intraperitoneal injection,model group,experimental group and DXMS group were injected with 0.5 ml LPS(5 mg/kg)in tail vein to construct ALI model.Normal group was injected with same amount of normal saline in tail vein.Rats were sacrificed 4 h after tail vein injection.HE staining to observe histopathological changes,TUNEL staining to detect cell apoptosis,DCFH-DA staining to detect reactive oxygen species(ROS)content,qRT-PCR,immunohistochemistry and Western blot to detect expressions of Nrf2 and HO-1.Results:Compared with normal group,apoptosis rate,ROS content,expressions of Nrf2 and HO-1 in lung tissue of model group were significantly increased,and ALI histopathology was obvious.Compared with model group,apoptosis rate and ROS content of lung tissue in experimental group and DXMS group were significantly decreased,expressions of Nrf2 and HO-1 were significantly increased,and pathological changes of ALI were significantly improved(P<0.05).Conclusion:Simvastatin can protect lung tissue of ALI rats by activating Nrf2/ARE pathway,increasing expressions of Nrf2 and HO-1,performing antioxidant effects,and inhibiting apoptosis.
作者
钱斌
尹小川
李小军
陈蔚
张敏
QIAN Bin;YIN Xiao-Chuan;LI Xiao-Jun;CHEN Wei;ZHANG Min(Department of Pharmacy,the First Affiliated Hospital of Kunming Medical University,Kunming 650032,China)
出处
《中国免疫学杂志》
CAS
CSCD
北大核心
2021年第18期2206-2211,共6页
Chinese Journal of Immunology
关键词
辛伐他汀
脂多糖
急性肺损伤
核因子E2相关因子2/抗氧化反应元件信号通路
Simvastatin
Lipopolysaccharide
Acute lung injury
Nuclear factor E2 related factor 2/antioxidant response element signaling pathway
