MCC950对急性胰腺炎大鼠的保护作用及其分子机制  

Protective Effect of MCC950 on Acute Pancreatitis in Rats and its Molecular Mechanism

作　　者：王增允 连颖 王丽君[1] 孙倩 王放[1] WANG Zeng-yun;LIAN Ying;WANG Li-jun;SUN Qian;WANG Fang(Department of Gastroenterology,the First Hospital of Qinhuangdao City,Qinhuangdao 066000,China)

机构地区：[1]秦皇岛市第一医院消化内科,河北秦皇岛066000

出　　处：《药物生物技术》2022年第2期150-153,166,共5页Pharmaceutical Biotechnology

基　　金：河北省科学技术成果奖(No.20182077)。

摘　　要：探讨了含NLR家族PYRIN域蛋白3(NACHT,LRR,and PYD domains-containing protein 3,NLRP3)抑制剂MCC950对急性胰腺炎大鼠的保护作用及其分子机制。将60只SD大鼠随机分为对照组、模型组和MCC950组,20只/组。模型组和MCC950组经手术注射5%牛黄胆酸钠制备急性胰腺炎模型,对照组给予假手术并注射生理盐水。建模后对照组和模型组一次性经腹腔注射生理盐水,MCC950组一次性经腹腔注射MCC95030 mg/kg,4 d后安乐处死大鼠,记录大鼠的生存情况及行为;采用自动生化仪检测血清淀粉酶活性;采用酶联免疫法检测各组血清中白细胞介素1β(Interleukin 1β,IL-1β)、白细胞介素6(Interleukin 6,IL-6)、肿瘤坏死因子(Tumor necrosis factor alpha,TNF-α)和白细胞介素18(Interleukin 18,IL-18)等炎症因子水平;采用HE染色观察各组胰腺组织病理学变化;采用TUNEL染色法分析各组胰腺细胞凋亡水平;采用Western blot分析各组胰腺组织NLRP3效应分子胱冬肽酶-1前体(pro-Caspase-1)、胱冬肽酶-1(Caspase-1)表达。对照组未见死亡,状态良好;模型组死亡3只,剩余大鼠少动、精神萎靡;MCC950组未见死亡,大鼠少动、精神萎靡等症状明显改善。与对照组比较,模型组血清淀粉酶活性、IL-1β、IL-6、TNF-α和IL-18等炎症因子、病理学评分、凋亡水平及Caspase-1蛋白显著增加(均P<0.05),胰腺组织中pro-Caspase-1蛋白水平显著降低(P<0.05);与模型组比较,MCC950组血清淀粉酶活性、IL-1β、IL-6、TNF-a和IL-18等炎症因子、病理学评分、凋亡水平及Caspase-1蛋白显著降低(均P<0.05),胰腺组织中pro-Caspase-1蛋白水平显著增高(P<0.05)。对照组胰腺组织纹理清晰,胰腺腺泡清晰,小叶结构完整,无炎症浸润、坏死和出血等;模型组胰腺组织可见明显水肿、出血和坏死,小叶间隙明显增加,大量炎症细胞浸润;MCC950组胰腺水肿、出血、坏死和炎症浸润明显缓解。MCC950可通过抑制NLRP3炎症小体活性下调炎To investigate the protective effect of MCC950,an inhibitor of NACHT,LRR,and PYD domains-containing protein 3(NLRP3),on acute pancreatitis in rats and its molecular mechanism,60 Sprague Dawley rats were randomly divided into 3 groups:the control group,the model group and the MCC950 group,20 rats/group.Rats in the model group and the MCC950 group were injected with 5%sodium taurocholate to prepare acute pancreatitis model,while rats in the control group were injected with same volume of normal saline solution.After modeling,rats in the control group and model group were intraperitoneally injected with normal saline solution at one time.The rats in the MCC950 group were intraperitoneally injected with 30 mg/kg MCC950 at one time.After4 days,the survival and behavior of all rats were recorded.The amylase activity in serum were detected by the automatic biochemical instrument.The interleukin 1β(IL-1β),interleukin 6(IL-6),tumor necrosis factor alpha(TNF-α)and interleukin 18(IL-18)were detected by the enzyme-linked immunoassay.The pathological changes of pancreatic tissue was detected by the HE staining.The apoptosis level of pancreatic tissues were detected by the TUNEL staining.The NLRP3 effector molecule Caspase-1 precursor(proCaspase-1)and caspase-1 were detected by the Western blot.There were no deaths in the control group,and they were in good condition.3 died in the model group,and the remaining rats were less active and lethargic.There were no deaths in the MCC950group,and the rats were less active and lethargic and other symptoms were significantly improved.Compared with the control group,the serum amylase activity,IL-1β,IL-6,TNF-α,IL-18,pathological scores,apoptosis and Caspase-1 protein in the model group increased significantly(all P<0.05),the level of pro-Caspase-1 protein in pancreatic tissue was significantly reduced(P<0.05).Compared with the model group,the serum amylase activity,IL-1β,IL-6,TNF-α,IL-18,pathology score,apoptosis and Caspase-1protein were significantly reduced(all P<0.05),and the l

关 键 词：MCC950 急性胰腺炎 含NLR家族PYRIN域蛋白3 淀粉酶 白细胞介素1Β 白细胞介素6 肿瘤坏死因子 白细胞介素18 

分 类 号：R576[医药卫生—消化系统]