PDF下载 ( 2226 KB)
Role and mechanism of the high-mobility group box 1/Toll-like receptor 9 signaling pathway in intestinal mucosal barrier injury in severe acute pancreatitis
-
摘要: 目的探讨高迁移率族蛋白B1（HMGB1）、Toll样受体（TLR） 9信号通路在重症急性胰腺炎（SAP）小鼠肠黏膜屏障损伤中的作用机制。方法将20只KM小鼠随机分为对照组和SAP组,每组10只。SAP组小鼠采用雨蛙素及脂多糖联合腹腔内注射建模,12 h后取材。HE染色观察小鼠胰腺病理学变化; ELISA检测小鼠血清二氨氧化酶（DAO）和内毒素核心抗体（Endo CAb）水平; TUNEL法检测小鼠小肠黏膜凋亡变化; Western Blot检测各组小鼠小肠HMGB1、TLR9、NF-κB蛋白水平的变化。计量资料2组间比较采用t检验。结果 SAP组小鼠均造模成功。SAP组小鼠血清DAO和EndoCAb水平明显高于对照组,差异有统计学意义（12. 172±1. 356 vs 4. 341±0. 521、32. 480±3. 054 vs 13. 281±2. 105,t值分别为16. 613、14. 725,P值分别为<0. 001、0. 025）; SAP组小鼠小肠黏膜细胞凋亡较对照组明显增加,差异有统计学意义（6. 25±2. 10 vs 19. 54±3. 63,t=11. 5...Abstract: Objective To investigate the role and mechanism of the high-mobility group box 1 ( HMGB1) /Toll-like receptor 9 ( TLR9) signaling pathway in intestinal mucosal barrier injury in mice with severe acute pancreatitis ( SAP) . Methods A total of KM mice were randomly divided into control group and SAP group. The mice in the SAP group were given intraperitoneal injection of cerulein and lipopolysaccharide to establish a model of SAP, and the samples were collected at 12 hours after modeling. HE staining was used to observe the pathological changes of the pancreas; ELISA was used to measure the serum levels of diamine oxidase ( DAO) and endotoxin core antibody ( EndoCAb) ; TUNEL was used to observe the apoptosis of intestinal mucosal cells; Western Blot was used to measure the changes in the protein expression of HMGB1, TLR9, and nuclear factor-kappa B ( NF-κB) in the small intestine. The t-test was used for comparison of normally distributed continuous data between two groups. Results A mouse model of SAP was successfully established. Compared with the control group, the SAP group had significantly higher serum levels of DAO ( 12. 172 ± 1. 356 vs 4. 341 ± 0. 521, t = 16. 613, P < 0. 001) and EndoCAb ( 32. 480 ± 3. 054 vs 13. 281 ± 2. 105, t = 14. 725, P = 0. 025) . Compared with the control group, the SAP group had a significant increase in apoptotic intestinal mucosal cells ( 19. 54 ± 3. 63 vs 6. 25 ± 2. 1, t = 11. 582, P < 0. 05) . Compared with the control group, the SAP group had significantly higher protein expression of HMGB1 ( 0. 590 ± 0. 004 vs 0. 059 ± 0. 035, t = 47. 336, P = 0. 001) , TLR 9 ( 0. 530 ± 0. 043 vs 0. 070 ± 0. 023, t = 30. 565, P = 0. 034) , and NF-κB ( 0. 670 ± 0. 059 vs 0. 170 ± 0. 032, t = 23. 655, P =0. 014) . Conclusion There is an increase in the expression of HMGB1 in the intestine of SAP mice, which may play an important role in intestinal mucosal barrier injury by activating the downstream TLR9 signaling pathway.
-
[1] SHEN X, LI WQ. High-mobility group box 1 protein and its role in severe acute pancreatitis[J]. World J Gastroenterol, 2015, 21 (5) :1424-1435. [2] YUAN H, JIN X, SUN J, et al. Protective effect of HMGB1 a box on organ injury of acute pancreatitis in mice[J]. Pancreas, 2009, 38 (2) :143-148. [3] WOLVEKAMP MC, de BRUIN RW. Diamine oxidase:An overview of historical, biochemical and functional aspects[J]. Dig Dis, 1994, 12 (1) :2-14. [4] CHEN X, ZHAO HX, BAI C. Blockade of high-mobility group box 1 attenuates intestinal mucosal barrier dysfunction in experimental acute pancreatitis.[J]. Sci Rep, 2017, 7:6799. [5] LI G, WU X, YANG L, et al. TLR4-mediated NF-κB signaling pathway mediates HMGB1-inducedy in pancreatic injur mice with severe acute pancreatitis[J]. Int J Mol Med, 2016, 37 (1) :99-107. [6] LUAN ZG, ZHANG XJ, YIN XH, et al. Downregulation of HMGB1protects against the development of acute lung injury after severe acute pancreatitis[J] Immunobiology, 2013, 218 (10) :1261-1270. [7] PAN LF, YU L, WANG LM, et al. Augmenter of liver regeneration (ALR) regulates acute pancreatitis via inhibiting HMGB1/TLR4/NF-κB signaling pathway[J]. Am J Transl Res, 2018, 10 (2) :402-410. [8] KANG R, ZHANG Q, HOU W, et al. Intracellular hmgb1 inhibits inflammatory nucleosome release and limits acute pancreatitis in mice[J]. Gastroenterology, 2014, 146 (4) :1097-1107. [9] ZHAO S, YANG J, LIU T, et al. Dexamethasone inhibits NF-кBp65 and HMGB1 expression in the pancreas of rats with severe acute pancreatitis[J]. Mol Med Rep, 2018, 18 (6) :5345-5352. [10] MANTI S, CUPPARI C, TARDINO L, et al. HMGB1 as a new biomarker of celiac disease in children:A multicenter study[J]. Nutrition, 2017, 37:18-21. [11] JIANG S, CHEN X. Expression of high-mobility group box 1protein (HMGB1) and Toll-like receptor 9 (TLR9) in retinas of diabetic rats[J]. Med Sci Monit, 2017, 23:3115-3122. [12] HOQUE R, SOHAIL M, MALIK A, et al. TLR9 and the NLRP3inflammasome link acinar cell death with inflammation in acute pancreatitis[J]. Gastroenterology, 2011, 141 (1) :358-369. [13] WANG YL, ZHENG YJ, ZHANG ZP, et al. Effects of gut barrier dysfunction and NF-kappaB activation on aggravating mechanism of severe acute pancreatitis[J]. J Dig Dis, 2009, 10 (1) :30-40. [14] LIU CS, WANG WX. Research progress on the mechanism of intestinal mucosal barrier injury in acute pancreatitis[J]. China Med Herald, 2019, 16 (3) :33-36. (in Chinese) 刘成思, 王卫星.急性胰腺炎肠黏膜屏障损伤机制的研究进展[J].中国医药导报, 2019, 16 (3) :33-36. 期刊类型引用(9)
1. 陈雪，林瑞珠，许建峰，李婷婷，李仕豪，童昕，田良，邹欢. 基于NF-κB p65信号通路探讨金汁修复受损的小鼠肠黏膜上皮细胞的机制. 现代中西医结合杂志. 2023(02): 171-176 . 
百度学术2. 裴柳，王术艺，赵运胜，左志刚，张梅香，赵丽坤，李开双，刘秀娟. 血清相关细胞因子水平预测重症急性胰腺炎患者肠道黏膜损伤的价值. 中国医师杂志. 2023(03): 397-401 . 百度学术3. 张晓鸣，刘彦茹，李斌彬，贾强，刘华清，王志仁. 血清连蛋白、高迁移率族蛋白B1水平与双相障碍患者认知功能和肠道菌群相对丰度的相关性分析. 现代生物医学进展. 2023(14): 2796-2800 . 百度学术4. 李慧，刘宇飞，李金龙，刘文君，薛虹，曹炫，刘欣. 蒲公英和板蓝根对LPS诱导的小鼠肠黏膜屏障损伤的调理机制研究. 中国预防兽医学报. 2023(08): 859-863+876 . 百度学术5. 杨昕，秦百君，唐曦平，郑日辉，陈小霞，谢彩杏，陈国忠. 清解化攻方调控HMGB1/TLR9/NF-κB信号通路对重症急性胰腺炎大鼠肠黏膜屏障保护作用的研究. 时珍国医国药. 2022(10): 2346-2349 . 百度学术6. 赖珊玲，曾清芳. 高迁移率族蛋白B1在胰腺疾病中的作用机制研究进展. 现代消化及介入诊疗. 2021(04): 451-453+459 . 百度学术7. 刘姗姗. MEWS评分下的预见性护理在急性重症胰腺炎患者中的应用观察. 临床研究. 2021(11): 160-162 . 百度学术8. 孙杰，诸海军，白金霞，赵连泽，万健. 重症急性胰腺炎合并腹腔感染患者外周血可溶性糖基化终末产物受体、内毒素、Toll样受体水平的变化研究. 中国医师进修杂志. 2021(11): 1045-1051 . 百度学术9. 王伟，涂华，张林菲，陈峰，潘俊，王恒. 中西医结合治疗对急性重症胰腺炎机体免疫功能的影响. 中华中医药学刊. 2020(07): 244-247 . 百度学术其他类型引用(4)
-
百度学术
下载:
