隐丹参酮调节Rac1/AKT/NF-κB信号通路对脓毒症大鼠肠损伤的影响  

Effect of Cryptotanshinone on Intestinal Injury in Septic Rats by Regulating the Rac1/AKT/NF-κB Signaling Pathway

作　　者：张树柳 刘瑞瑞 陈玉刚 杜超 崔云亮 ZHANG Shuliu;LIU Ruirui;CHEN Yugang(th Hospital of the Joint Logistic Support Force of the People's Liberation Army,Shandong Ji'nan 250031,China)

机构地区：[1]解放军联勤保障部队第九六〇医院重症医学科,山东济南250031

出　　处：《河北医学》2024年第10期1597-1603,共7页Hebei Medicine

基　　金：山东省医药卫生科技发展计划项目,(编号:202117011071)。

摘　　要：目的:探究隐丹参酮(CRY)调节Ras相关C3肉毒素底物1(Racl)/丝氨酸-苏氨酸蛋白酶(AKT)/核转录因子-κB(NF-κB)信号通路对脓毒症大鼠肠损伤的影响。方法:建立脓毒症大鼠模型。大鼠分为Control组、Model组、隐丹参酮高、中、低剂量组(7.0mg·kg^(-1)·d^(-1)CRY-H组、14.0mg·kg^(-1)·d^(-1)CRY-M组、28.0mg·kg^(-1)·d^(-1)CRY-L组)和隐丹参酮高剂量+NF-κB通路激活剂组(28mg·kg^(-1)·d^(-1)CRY-H+5 mg·kg^(-1)·d^(-1)PMA组),每组12只,Control组与Model组使用同等剂量生理盐水进行处理,每天1次,连续21d。用试剂盒检测脓毒症大鼠血清炎症因子、氧化应激、肠黏膜屏障指标水平;HE染色观察大鼠肠组织病理形态;免疫组化和免疫印迹法分别检测大鼠肠组织中ZO-1、occludin和通路蛋白表达。结果:与Control组比较,Model组黏膜绒毛排列紊乱,部分黏膜脱落、坏死,大量炎细胞浸润,组织病理评分较高,血清TNF-α、IL-1β、MDA、内毒素、D-乳酸水平上升,SOD水平降低,Rac1、p-AKT/AKT、p-NF-κB/NF-κB表达上调,ZO-1、occludin下调表达(P<0.05);与Model组比较,CRY-L、CRY-M、CRY-H组肠黏膜绒毛相对完整,炎细胞浸润减轻,组织病理评分降低,血清TNF-α、IL-1β、MDA、内毒素、D-乳酸水平降低,SOD水平上升,Rac1、p-AKT/AKT、p-NF-κB/NF-κB表达下调,ZO-1、occludin上调表达(P<0.05);与CRY-H组相比,CRY-H+PMA组肠黏膜细胞有较多炎细胞浸润,组织病理评分升高,血清TNF-α、IL-1β、MDA、内毒素、D-乳酸水平升高,SOD水平降低,Rac1、p-AKT/AKT、p-NF-κB/NF-κB表达上调,ZO-1、occludin下调表达(P<0.05)。结论:隐丹参酮抑制Rac1/AKT/NF-κB信号通路改善脓毒症大鼠肠损伤。Objective:To investigate the effect of cryptotanshinone(CRY)on intestinal injury in septic rats by regulating the Ras related C3 botulinum toxin substrate 1(Racl)/serine threonine protease(AKT)/nuclear factor kappa B(NF-κB)signaling pathway.Methods:Sepsis rat models were established and grouped into control group,model group,high-dose,medium,and low-dose cryptotanshinone groups(7.0mg·kg^(-1)·d^(-1)CRY-H group,14.0mg·kg^(-1)·d^(-1)CRY-M group,28.0mg·kg^(-1)·d^(-1)CRY-L group),and high-dose cryptotanshinone+NF-κB pathway activator group(28.0mg·kg^(-1)·d^(-1)CRY-H+5.0mg·kg^(-1)·d^(-1)PMA group),with 12 rats in each group.The control group and the model group were treated with the same dose of normal saline once a day for 21 consecutive days.The levels of serum inflammatory factors,oxidative stress and intestinal mucosal barrier indexes in sepsis rats were detected by kit.HE staining was used to observe the pathological morphology of intestinal tissue in rats.The expressions of ZO-1,occludin and pathway proteins in intestinal tissues of rats were detected by immunohistochemistry and Western blotting,respectively.Results:Compared with the control group,the mucosal villi in the model group were disorderly arranged,with some mucosa shedding and necrosis,a large number of inflammatory cells infiltrating,the histopathological score was higher,the serum levels of TNF-α,IL-1β,MDA,endotoxin,and D-lactate increased,the level of SOD decreased,the expression of Rac1,p-AKT/AKT,p-NF-κB/NF-κB was upregulated,while ZO-1 and occludin were downregulated(P<0.05).Compared with the model group,the CRY-L,CRY-M,and CRY-H groups had relatively intact intestinal mucosal villi,inflammatory cell infiltration reduced,and histopathological scores decreased,the serum levels of TNF-α,IL-1β,MDA,endotoxin,and D-lactate decreased,the level of SOD increased,the expression of Rac1,p-AKT/AKT,p-NF-κB/NF-κB was downregulated,while ZO-1 and occludin were upregulated(P<0.05).Compared with the CRY-H group,the CRY-H+PMA group had more inf

关 键 词：脓毒症 隐丹参酮 Ras相关C3肉毒素底物1/丝氨酸-苏氨酸蛋白酶/核转录因子-κB信号通路 肠损伤 

分 类 号：R285.5[医药卫生—中药学]