红景天苷调控NF-κB/NALP3信号通路对重症急性胰腺炎大鼠肠黏膜屏障损伤的保护作用  

Protective effect of salidroside on intestinal mucosal barrier injury in rats with severe acute pancreatitis by regulating the NF-κB/NALP3 signaling pathway

作　　者：张莹[1] 潘诗翰 康亮 梁蓓薇[2] 万瑞融[3] ZHANG Ying;PAN Shihan;KANG Liang(Pharmaceutical College Guangxi Medical University,Guangxi,Nanning 530021,China)

机构地区：[1]广西医科大学药学院,南宁市530021 [2]广西医科大学第一附属医院心血管病研究所导管手术麻醉室,南宁市530021 [3]广西医科大学第一附属医院药学部,南宁市530021

出　　处：《河北医药》2023年第21期3221-3225,共5页Hebei Medical Journal

基　　金：广西壮族自治区卫生健康委员会自筹经费科研课题(编号:Z20200996)。

摘　　要：目的 探讨红景天苷(SAL)对重症急性胰腺炎(SAP)大鼠的保护作用及其机制。方法 将32只健康SD大鼠随机分为假手术(Sham)组、SAP组、SAL(4.0 mg/kg)组和阳性对照乌司他丁(ULI,2×10~4 U/kg)组,每组8只。除Sham组外,其他各组以胆胰管逆行注射5%牛磺胆酸钠溶液法建立SAP大鼠模型。4组于术前2 h腹腔注射相应药物。采用酶联免疫吸附实验(ELISA)法检测血清淀粉酶、内毒素(ET)、二胺氧化酶(DAO)、白细胞介素(IL)-1β、IL-6和肿瘤坏死因子-α(TNF-α)水平,苏木精-伊红(HE)染色法观察胰腺组织和回肠组织病理改变。免疫荧光染色法检测回肠组织中NF-κBp65磷酸化(p-p65)表达。Western blotting法检测回肠组织中NF-κBp65、p-p65、NALP3、ASC、caspase-1和cleaved caspase-1表达。结果 SAP组大鼠胰腺组织和肠组织较Sham组损伤严重,血清淀粉酶、ET、DAO、IL-1β、IL-6、TNF-α水平升高,肠组织NF-κB p-p65、NALP3、caspase-1、ASC蛋白表达升高(P<0.05);与SAP组比较,SAL组、ULI组胰腺组织和肠组织病理损伤减轻,血清淀粉酶、ET、DAO、IL-1β、IL-6、TNF-α含量及肠组织NF-κB p-p65、NALP3、caspase-1、ASC蛋白水平降低(P<0.05)。SAL组与ULI组上述指标比较,差异均无统计学意义(P>0.05)。结论 SAL可能通过抑制NF-κB/NALP3炎性体信号通路减轻炎性反应,保护SAP大鼠肠黏膜屏障损伤。Objective To investigate the protective effect of salidroside(SAL)on severe acute pancreatitis(SAP)in rats and the underlying mechanism.Methods A total of 32 healthy Sprague-Dawley(SD)rats were randomly divided into Sham group,SAP group,SAL group(4.0mg/kg)and ulinastatin group(ULI,positive control,2×104 U/kg),with 8 rats in each group.Except for the Sham group,SAP rat model was established in the remaining groups by retrograde injection of 5%sodium taurocholate solution into the biliary pancreatic duct.Intraperitoneal administration of corresponding drugs was performed 2h before the modeling.Serum amylase,endotoxin(ET),diamine oxidase(DAO),interleukin(IL)-1β,IL-6 and tumor necrosis factor-α(TNF-α)levels were detected by enzyme-linked immunosorbent assay(ELISA).Hematoxylin&eosin(H&E)staining was performed to visualize the pathological changes in rat pancreatic and ileal tissues.The expression of phosphorylated NF-κBp65(p-p65)in ileum tissues was detected by immunofluorescence staining.The protein expressions of nuclear factor-kappaBp65(NF-kBp65),phosphorylated-p65(p-p65),NACHT-LRRPYD-containing protein 3(NALP3),apoptosis-associated speck-like protein containing(ASC),caspase-1 and cleaved caspase-1 in ileum tissues were detected by Western blotting.Results Compared with the Sham group,the pancreatic and intestinal tissues in SAP group were more seriously damaged,and serum amylase,ET,DAO,IL-1β,IL-6 and TNF-αlevels and expressions of NF-kBp65,p-p65,NALP3,caspase-1 and ASC in ileum were significantly higher(P<0.05).Compared with the SAP group,the pancreatic and intestinal tissues in SAL and ULI group were alleviated,and serum amylase,ET,DAO,IL-1β,IL-6 and TNF-αlevels and expressions of NF-kBp65,p-p65,NALP3,caspase-1 and ASC in ileum were significantly lower(P<0.05).There were no significant differences in the above indexes between SAL and ULI group(P>0.05).Conclusion SAL reduces the inflammatory response by inhibiting the NF-κB/NALP3 inflammasome signaling pathway,thereby protecting the intestinal mucosal ba

关 键 词：红景天苷 重症急性胰腺炎 炎症 NALP3 肠黏膜屏障损伤 

分 类 号：R576.9[医药卫生—消化系统]