基于lncRNA/miRNA/NF-κB通路探讨大黄玄明粉对急性胰腺炎大鼠全身炎症和肠道损伤的保护作用及机制  

Protective Effect of Rhubarb Xuanming Powder on Systemic Inflammation and Intestinal Injury in Rats with Acute Pancreatitis and its mechanism analysis based on lncRNA/miRNA/NF-κB pathway

作　　者：黄广文 周正 何锦雄 温玉平 HUANG Guang-wen;ZHOU Zheng;HE Jin-xiong;WEN Yu-ping(Department of Spleen and Stomach Diseases,Dongguan Traditional Chinese Medicine Hospital,Dongguan,Guangdong 523419,China)

机构地区：[1]东莞市中医院脾胃病科,523419

出　　处：《现代消化及介入诊疗》2024年第3期297-301,306,共6页Modern Interventional Diagnosis and Treatment in Gastroenterology

基　　金：广东省中医药局科研项目(20221421)。

摘　　要：目的观察大黄玄明粉对急性胰腺炎(SAP)大鼠全身炎症和肠道损伤的保护作用及对lncRNA/miRNA/NF-κB通路的影响,探讨大黄玄明粉对急性胰腺炎的治疗作用机制。方法雄性SD大鼠60只分为用药组(n=20)、模型组(n=20)和假手术组(n=20)。用药组和模型组大鼠均通过逆行胆胰管注射牛磺胆酸钠溶液建立SAP大鼠模型,假手术组只进行胆胰管分离但不穿刺。此外,自建模操作后1h开始,三组大鼠均每12 h灌胃1次,连续6次,用药组采用大黄玄明粉冲剂(1 mL/100 g)灌胃,模型组和假手术组采用等体积生理盐水灌胃。末次灌胃后12 h,各组大鼠均进行疾病活动指数(DAI)评价;抽取腹主动脉血检测血清淀粉酶、脂肪酶、D-乳酸、二胺氧化酶(DAO)、内毒素及炎症因子(IL-6、TNF-α)水平;并取胰腺组织和结肠黏膜组织行HE染色观察确定胰腺病理评分和结肠黏膜组织Chiu评分,并分别采用RT-PCR法和western blot法进行lncRNA DGCR9/MiR-342-5p/Akt/NF-κB通路相关因子转录和蛋白水平表达检测。结果三组DAI、胰腺病理评分和结肠黏膜组织Chiu评分比较,模型组>用药组>假手术组(P<0.05)。三组血清淀粉酶、脂肪酶、D-乳酸、DAO、内毒素、IL-6、TNF-α水平比较,模型组>用药组>假手术组(P<0.05)。三组lncRNA DGCR9、Akt的转录表达水平比较,模型组<用药组<假手术组(P<0.05);三组MiR-342-5p、NF-κB p65的转录表达水平比较,模型组>用药组>假手术组(P<0.05)。三组p-Akt蛋白表达水平比较,模型组<用药组<假手术组(P<0.05);三组NF-κB p65蛋白表达水平比较,模型组>用药组>假手术组(P<0.05)。结论大黄玄明粉可减轻急性胰腺炎大鼠的胰腺病理损伤和结肠黏膜损伤,其机制可能与调控lncRNA DGCR9/MiR-342-5p/Akt/NF-κB通路从而抑制炎症反应有关。Objective To observe the protective effect of rhubarb Xuanming powder on systemic inflammation and intestinal injury in rats with acute pancreatitis(SAP),as well as its effect on lncRNA/miRNA/NF-κB pathway,so as to explore the therapeutic mechanism of rhubarb Xuanming powder on acute pancreatitis.Methods 60 male SD rats were divided into medication group(n=20),model group(n=20)and sham surgery group(n=20).Both of the medication group and the model group rats established SAP rat models by retrograde injection of sodium taurocholate solution into the biliopancreatic duct,while the sham surgery group only underwent biliary and pancreatic duct separation without puncture.In addition,from 1 hour after the modeling operation,the three groups of rats were gavaged once every 12 hours for 6 consecutive times.The medication group was gavaged with Dahuang Xuanming Powder Granule(1ml/100g),while the model group and sham operation group were gavaged with equal volume physiological saline.12 hours after the last gavage,disease activity index(DAI)was evaluated in all groups of rats;Abdominal aortic blood was extracted for detection of serum amylase,lipase,D-lactate,diamine oxidase(DAO),endotoxin,and inflammatory factors(IL-6,TNF)-αlevel;And pancreatic tissue and colonic mucosal tissue were taken for HE staining observation to determine the pancreatic pathological score and colonic mucosal tissue Chiu score,and transcription and protein expression of lncRNA DGCR9/MiR-342-5p/Akt/NF-κB pathway related factors were measured using RT-PCR and Western blot methods respectively.Results The comparison of DAI,pancreatic pathology score,and colonic mucosal tissue Chiu score among the three groups showed that the model group>medication group>sham surgery group(P<0.05).Comparison of serum amylase,lipase,D-lactate,DAO,endotoxin,IL-6,TNF-αlevel of three groups showed that the model group>medication group>sham surgery group(P<0.05).Comparison of the transcriptional expression levels of lncRNA DGCR9 and Akt among three groups showed that mo

关 键 词：大黄 玄明粉 急性胰腺炎 长链非编码RNA 核因子ΚB MiR-342-5p 全身炎症 肠道损伤 

分 类 号：R576[医药卫生—消化系统]