罗汉果醇通过TREM-1/NLRP3通路介导的细胞焦亡对重症急性胰腺炎大鼠肺损伤的影响  

Effect of Mogrol on Lung Injury in Rats with Severe Acute Pancreatitis via Cell Pyroptosis Mediated by TREM-1/NLRP3 Pathway

作　　者：陈玉梅 杨静 苏淼 董梁 王丽华 CHEN Yumei;YANG Jing;SU Miao;DONG Liang;WANG Lihua(Hengshui People's Hospital,Hengshui 053000,China)

机构地区：[1]衡水市人民医院,衡水053000

出　　处：《世界科学技术-中医药现代化》2024年第3期844-851,共8页Modernization of Traditional Chinese Medicine and Materia Medica-World Science and Technology

基　　金：衡水市科学技术局科技计划项目(2018014008Z):腹消炎联合生长抑素、奥美拉挫治疗急性胰腺炎的临床研究,负责人:杨静;。

摘　　要：目的探讨罗汉果醇对重症急性胰腺炎大鼠肺损伤的影响及其可能的作用机制。方法采用胰胆管逆行注射4%牛磺胆酸钠构建重症急性胰腺炎大鼠肺损伤模型,造模后分为模型组、罗汉果醇低、中、高剂量组(15、30、60 mg·kg^(-1)),另设置假手术组,每组12只。腹腔注射给药,每天1次,共2次。HE染色检测大鼠胰腺及肺组织病理学变化;生化法检测大鼠血清淀粉酶(AMS)、脂肪酶(LPS)水平;ELISA法检测大鼠肺泡灌洗液中炎症因子白介素1β(IL-1β)、白介素18(IL-18)及肿瘤坏死因子α(TNF-α)水平;比色法检测大鼠肺组织中Caspase-1活性;Western blot检测大鼠肺组织中髓样细胞触发受体-1(TREM-1)蛋白和焦亡相关蛋白NLRP3、Caspasse-1、Gasdermin D(GSDMD)等蛋白表达水平。结果与假手术组比较,模型组大鼠胰腺和肺组织出现明显的病理学损伤,血清AMS和LPS水平、炎症因子IL-1β、IL-18及TNF-α水平、Caspase-1活性以及肺组织中TREM-1、NLRP3、Caspasse-1、GSDMD等蛋白表达水平均显著性升高(P<0.05);与模型组比较,不同剂量罗汉果醇干预可改善大鼠胰腺及肺组织病理学损伤,同时显著降低血清AMS、LPS,炎症因子IL-1β、IL-18、TNF-α,Caspase-1活性和肺组织中TREM-1、NLRP3、Caspasse-1、GSDMD等蛋白表达水平。结论罗汉果醇可能通过抑制细胞焦亡改善重症急性胰腺炎大鼠肺损伤,其作用机制可能与调控TREM-1/NLRP3信号通路有关。Objective To investigate the effect of mogrol on lung injury in rats with severe acute pancreatitis and its possible mechanism.Methods The model of lung injury in rats with severe acute pancreatitis was established by retrograde injection of 4%sodium taurocholate into the biliopancreatic duct,After modeling,they were divided into model group,mogrol low,medium and high dose groups(15,30,60 mg·kg^(-1)),set up another sham operation group,each group containing 12 rats.Intraperitoneal injection,one day once time,a total of 2 times.The pathological changes of pancreas and lung tissues were detected by HE staining;Serum amylase(AMS)and lipase(LPS)levels were detected by biochemical method;The levels of inflammatory cytokines interleukin-1β(IL-1β),interleukin-18(IL-18)and tumor necrosis factor-α(TNF-α)in rat alveolar lavage fluid were determined by ELISA;The activity of Caspase-1 in lung tissue of rats was detected by colorimetry;The expression levels of triggering receptor 1(TREM-1)and pyroptosis related proteins NLRP3,Caspasse-1,Gasdermin D(GSDMD)in lung tissue of rats were detected by Western blot.Results Compared with the sham operation group,the model group showed obvious pathological damage in pancreas and lung tissue.Serum AMS and LPS levels,inflammatory factors IL-1β,IL-18 and TNF-αlevels,Caspase-1 activity,and protein expression levels of TREM-1 and NLRP3,Caspasse-1,GSDMD,in lung tissue were significantly increased(P<0.05);Compared with the model group,different doses of mogrol could improve the pathological damage of pancreas and lung tissue in rats,and significantly reduce the levels of serum AMS,LPS,inflammatory factors IL-1β,IL-18 and TNF-α,Caspase-1 activity and the expression levels of TREM-1 and NLRP3,Caspasse-1,GSDMD in lung tissue.Conclusion Mogrol may improve lung injury in rats with severe acute pancreatitis by inhibiting pyroptosis,and its mechanism may be related to the regulation of TREM-1/NLRP3 signaling pathway.

关 键 词：罗汉果醇 重症急性胰腺炎 肺损伤 细胞焦亡 髓样细胞触发受体-1 

分 类 号：R285.5[医药卫生—中药学]