摘要
目的:探讨虫草素对急性呼吸窘迫综合征(ARDS)大鼠肺组织损伤的影响及作用机制。方法:60只Wistar大鼠随机分为对照组、脂多糖组(LPS)、虫草素低剂量组(5 mg/kg)、虫草素中剂量组(15 mg/kg)、虫草素高剂量组(30 mg/kg)、Compound C组(虫草素高剂量30 mg/kg+AMPK抑制剂15 mg/kg),每组10只。构建LPS大鼠ARDS模型,HE染色观察大鼠肺组织病理变化并进行肺组织病理损伤评分;检测大鼠肺湿/干重比(W/D);检测髓过氧化物酶(MPO)活性;ELISA检测IL-6、IL-1β、TNF-α水平;试剂盒检测丙二醛(MDA)、超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH)水平;Western blot检测腺苷酸活化蛋白激酶(AMPK)、p-AMPK、雷帕霉素靶蛋白(mTOR)、p-mTOR、P70核糖体蛋白S6激酶(p70S6K)、p-p70S6K蛋白表达。结果:相比于对照组,LPS组大鼠肺组织受损明显,大量炎症细胞浸润,肺W/D、肺组织损伤病理评分、MPO活性、IL-6、IL-1β、TNF-α、MDA水平升高,p-mTOR/mTOR、p-p70S6K/p70S6K蛋白表达升高(P<0.05),SOD、GSH水平降低,p-AMPK/AMPK蛋白表达降低(P<0.05);虫草素治疗后肺组织损伤减轻,少量炎症细胞浸润,肺W/D、肺组织损伤病理评分、MPO活性、IL-6、IL-1β、TNF-α、MDA水平降低,p-mTOR/mTOR、p-p70S6K/p70S6K蛋白表达降低(P<0.05),SOD、GSH水平升高,p-AMPK/AMPK蛋白表达升高(P<0.05);而AMPK抑制剂Compound C逆转了虫草素对ARDS大鼠肺损伤的改善作用。结论:虫草素能改善LPS诱导的大鼠肺组织损伤,降低炎症和氧化应激水平,其作用机制可能与调节AMPK/mTOR/p70S6K通路有关。
Objective:To investigate effect of cordycepin on lung injury in rats with acute respiratory distress syndrome(ARDS)and its mechanism.Methods:Sixty Wistar rats were randomly divided into control group,lipopolysaccharide group(LPS),cordyce-pin low-dose group(5 mg/kg),cordycepin medium-dose group(15 mg/kg),cordycepin high-dose group(30 mg/kg),Compound C group(high-dose cordycepin 30 mg/kg+AMPK inhibitor 15 mg/kg),with 10 rats in each group.ARDS model of LPS rats was estab-lished,pathological changes of lung tissues were observed by HE staining and lung tissue pathological injury score was performed;wet/dry weight ratio(W/D)of rat lungs was measured;activity of myeloperoxidase(MPO)was detected;IL-6,IL-1βand TNF-αwere measured by ELISA;malondialdehyde(MDA),superoxide dismutase(SOD)and glutathione peroxidase(GSH)were detected by kit;Western blot was used to detect expressions of AMP-activated protein kinase(AMPK),p-AMPK,mammalian target of rapamy-cin(mTOR),p-mTOR,P70 ribosomal protein S6 kinase(p70S6K)and p-p70S6K.Results:Compared with control group,rats in LPS group had obvious lung tissue damage,and a large number of inflammatory cells infiltration,lung W/D,pathological injury score of lung tissue,MPO activity,IL-6,IL-1β,TNF-α,MDA levels were increased,p-mTOR/mTOR,p-p70S6K/p70S6K protein expres-sions were increased(P<0.05),SOD,GSH levels were decreased,p-AMPK/AMPK protein expression was decreased(P<0.05);after treatment with cordycepin,lung tissue damage was reduced,a small amount of inflammatory cells were infiltrated,lung W/D,pathological injury score of lung tissue,MPO activity,IL-6,IL-1β,TNF-α,MDA levels were decreased,p-mTOR/mTOR,p-p70S6K/p70S6K protein expressions were decreased(P<0.05),SOD,GSH levels were increased,p-AMPK/AMPK protein expressions were increased(P<0.05);AMPK inhibitor Compound C reversed improvement of cordycepin on lung injury in ARDS rats.Conclusion:Cordycepin can improve LPS induced lung injury of rats,reduce inflammatory and oxidative stress,whose mechanism may be related to regulation of AMPK/mTOR/p70S6K pathway.
作者
白冬梅
蓝群盛
许耿瑞
吴丽霞
刘江红
BAI Dongmei;LAN Qunsheng;XU Gengrui;WU Lixia;LIU Jianghong(Pharmacy Department of Shenzhen Longhua District Central Hospital,Shenzhen 518110,China)
出处
《中国免疫学杂志》
北大核心
2025年第8期1885-1889,共5页
Chinese Journal of Immunology
基金
深圳市龙华区科技创新项目(2020036)。
