白藜芦醇诱导NOD样受体蛋白结构域相关蛋白3炎性体轴致胰腺腺泡细胞凋亡的机制  

Study on the mechanism of resveratrol on pancreatic acinus apoptosis in rats with severe acute pancreatitis based on NOD like receptor pyrin domain containing 3 inflammatory body axis

作　　者：宋宗工 王翃 周学伟[1] 朱长举[3] SONG Zonggong;WANG Hong;ZHOU Xuewei;ZHU Changju(Minimally Invasive Surgery of Nanyang Second People’s Hospital,Nanyang 473000,China;Department of Gastroenterology,Nanyang Second People’s Hospital,Nanyang 473000,China;Department of Emergency,the First Affiliated Hospital of Zhengzhou University,Zhengzhou 450000,China)

机构地区：[1]南阳市第二人民医院微创外科,南阳473000 [2]南阳市第二人民医院消化内科,南阳473000 [3]郑州大学第一附属医院急诊科,郑州450000

出　　处：《西北药学杂志》2024年第3期52-58,共7页Northwest Pharmaceutical Journal

基　　金：河南省医学科技攻关计划联合共建项目(编号:LHGJ20210977)。

摘　　要：目的探讨白藜芦醇对重症急性胰腺炎(severe acute pancreatitis,SAP)大鼠胰腺腺泡细胞凋亡的影响及对NOD样受体蛋白结构域相关蛋白3(NOD like receptor pyrin domain containing 3,NLRP3)炎性体轴的调节作用。方法将50只大鼠随机分为假手术组、模型组和白藜芦醇低、高剂量组及地塞米松组,每组10只,除假手术组大鼠外,其余组大鼠通过牛黄胆酸钠逆行胰胆管注射制备SAP模型。手术结束5 min后,白藜芦醇低、高剂量组分别腹腔注射白藜芦醇30、60 mg·kg^(-1),地塞米松组大鼠腹腔注射地塞米松2 mg·kg^(-1),每日1次,连续给药3 d,假手术组和模型组大鼠腹腔注射等量生理盐水。检测大鼠血清中淀粉酶和脂肪酶活性,白细胞介素(IL)-1β、IL-18和肿瘤坏死因子α(tumor necrosis factorα,TNF-α)含量,检测胰腺组织病理损伤并进行病理评分,胰腺腺泡细胞凋亡指数以及NLRP3、天冬氨酸特异性半胱氨酸蛋白酶1(caspase-1)、B细胞淋巴瘤-2(B-cell lymphoma-2,Bcl-2)和Bcl-2相关X蛋白(Bcl-2 associated X protein,Bax)的蛋白相对表达量。结果假手术组大鼠胰腺组织结构正常,无水肿、充血或坏死;模型组胰腺间质水肿,肺泡间隔变宽,可见大量炎性细胞浸润,实质出现点状或片状出血或坏死;白藜芦醇低、高剂量组和地塞米松组胰腺组织病变程度均减轻。与假手术组比较,模型组淀粉酶和脂肪酶活性,IL-1β、IL-18和TNF-α含量,组织病理评分,细胞凋亡指数及NLRP3、caspase-1和Bax蛋白的相对表达量均升高,Bcl-2蛋白相对表达量降低(P<0.05);与模型组比较,白藜芦醇低、高剂量组和地塞米松组淀粉酶和脂肪酶活性,IL-1β、IL-18和TNF-α含量,组织病理评分,细胞凋亡指数及NLRP3、caspase-1和Bax蛋白的相对表达量均降低,Bcl-2蛋白相对表达量升高(P<0.05);与白藜芦醇低剂量组比较,高剂量组和地塞米松组淀粉酶和脂肪酶活性,IL-1β、IL-18和TNF-α含量,组织病理评分,�Objective To investigate the effect of resveratrol on apoptosis of pancreatic acinar cells in rats with severe acute pancreatitis(SAP)and modulating the inflammatory body axis of NOD like receptor pyrin domain containing 3(NLRP3).Methods 50 rats were randomly divided into sham operation group,model group,low-dose resveratrol group,high-dose resveratrol group and dexamethasone group,with 10 rats in each group.Except for the sham operation group,the SAP model was prepared by retrograde injection of sodium bezoar cholate in other groups.5 minutes after the operation,the low-dose and high-dose resveratrol groups were intraperitoneally injected with 30 and 60 mg·kg^(-1) resveratrol,the dexamethasone group was intraperitoneally injected with 2 mg·kg^(-1) dexamethasone,once a day for consecutive 3 days,and the sham operation group and model group were intraperitoneally injected with the same amount of normal saline.The contents of amylase,lipase,interleukin(IL)-1β,IL-18 and tumor necrosis factorα(TNF-α)in serum of rats were detected,The pathological damage of pancreatic tissue was detected and recorded in histopathological score,and the apoptosis index of pancreatic acinar cells was detected.The protein relative expression levels of NLRP3,aspartic acid specific cysteine protease 1(caspase-1),B-cell lymphoma-2(Bcl-2)and Bcl-2 associated X protein(Bax)were also detected.Results In sham operation group,the pancreas tissue structure was normal without edema,hyperemia or necrosis.In model group,pancreatic interstitial edema was observed,alveolar septum widened,a large number of inflammatory cell infiltration,and punctate or lamellar hemorrhage or necrosis occurred in the parenchyma.The degree of pancreatic tissue lesion was reduced in the low-dose,high-dose resveratrol groups and dexamethasone group.Compared with sham operation group,the contents of amylase and lipase,IL-1β,IL-18 and TNF-α,histopathological score,apoptosis index and the relative expression levels of NLRP3,caspase-1 and Bax proteins in model group were

关 键 词：白藜芦醇 重症急性胰腺炎 凋亡 NOD样受体蛋白结构域相关蛋白3 

分 类 号：R965[医药卫生—药理学]