摘要
目的:探讨红景天苷(SAL)对肠缺血再灌注损伤(IIR)大鼠硫氧还蛋白相互作用蛋白(TXNIP)/NOD样受体蛋白3(NLRP3)信号通路及肠黏膜功能的影响。方法:60只成年雄性SD大鼠随机分为假手术组(对照组)、模型组、低剂量组(红景天苷10 mg/kg)、中剂量组(红景天苷20 mg/kg)、高剂量组(红景天苷40 mg/kg),每组12只。建立肠缺血再灌注模型前24 h、12 h和1 h低、中、高剂量组分别给予10 mg/kg、20 mg/kg、40 mg/kg红景天苷预处理,模型组给予生理盐水处理。对照组不建立模型,且给予生理盐水处理。再灌注2 h后取材,计算小肠含水率;采用酶联免疫吸附(ELISA)试剂盒检测血清中白细胞介素18(IL-18)、白细胞介素1β(IL-1β)和白细胞介素10(IL-10)水平;以苏木精—伊红染色(HE)检测各组大鼠小肠黏膜组织病理变化;检测小肠组织中丙二醛(MDA)含量和超氧化物歧化酶(SOD)活性,以蛋白免疫印迹法(Western blotting)检测小肠组织中TXNIP/NLRP3通路蛋白表达。结果:HE染色结果显示,对照组大鼠小肠组织无明显肠黏膜损伤,模型组大鼠肠黏膜损伤明显,低剂量组绒毛结构保留,中剂量组多数绒毛完整,高剂量组绒毛结构接近正常;与对照组相比,模型组大鼠小肠含水率、血清炎性因子IL-18、IL-1β水平、小肠组织中MDA水平及TXNIP、NLRP3、Cleaved Caspase-1 p20蛋白表达均显著升高,IL-10水平及SOD活性显著降低(均P<0.05)。与模型组相比,低剂量组、中剂量组、高剂量组小肠含水率、血清炎性因子IL-18、IL-1β水平、小肠组织中MDA水平及TXNIP、NLRP3、Cleaved Caspase-1 p20蛋白表达均显著降低,IL-10水平及SOD活性显著升高,具有一定的剂量依赖性(均P<0.05)。结论:红景天苷可能通过减轻氧化应激反应,抑制TXNIP∕NLRP3信号通路及其下游炎症反应,保护肠黏膜,减轻IIR。
Objective:To investigate the effects of salidroside(SAL)on thioredoxin-interacting protein(TXNIP)/NOD-like receptor protein 3(NLRP3)signaling pathway and intestinal mucosal function in rats with intestinal ischemia-reperfusion injury.Methods:Sixty adult male SD rats were randomly divided into sham operation group(control group),model group,salidroside low-dose group(10 mg/kg),salidroside medium dose group(20 mg/kg)and salidroside high dose group(40 mg/kg),with 12 rats in each group.At 24 h,12 h and 1h before establishing intestinal ischemia-reperfusion model,the salidroside low-dose group,middle-dose group,and high-dose group were pretreated with salidroside at the dose of 10 mg/kg,20mg/kg,and 40 mg/kg,respectively,and the model group rats were treated with normal saline.The rats in control group did not establish model and were treated with normal saline.After 2 h of reperfusion,the small intestinal tissues were taken to calculate the small intestinal water content;the levels of interleukin-18(IL-18),interleukin-1β(IL-1β)and interleukin-10(IL-10)were detected by enzyme-linked immunosorbent assay(ELISA);hematoxylin eosin staining(HE)was used to detect the pathological changes of small in-testinal mucosa;malondialdehyde(MDA)and superoxide dismutase(SOD)in small intestinal tissue were detected,and the expression of TXNIP/NLRP3 pathway protein in small intestinal tissue was detected by Western blotting.Results:HE staining showed that there was no obvious intestinal mucosal damage in the sham operation group,and obvious damage was found in the model group;the villus structure was preserved in the low-dose group,most of the villi in the medium dose group were intact,and the villi structure in the high-dose group was close to normal.Compared with control group,the levels of IL-18 and IL-1βin serum,MDA level in small intestinal tissue,and TXNIP,NLRP3,cleaved caspase-1 p20 protein expressions in model group were significantly higher,while the IL-10 and SOD levels were significantly lower(P<0.05).Compared with the mode
作者
钟旭
唐国强
刘迁
黄政
许滔
Zhong Xu;Tang Guoqiang;Liu Qian;Huang Zheng;Xu Tao(Zigong First People's Hospital,Zigong 643000,China)
出处
《广西医科大学学报》
CAS
2021年第8期1517-1523,共7页
Journal of Guangxi Medical University
基金
四川省医学(青年创新)科研计划资助项目(No.S19008)。
