Study on treatment of severe acute pancreatitis with Dachengqi Decoction through inhibition of HMGB1 and NLRP3 inflammasomes

Jie LI; Zhuoan CHENG; Jiaoyang MA; Dianxu FENG; Yafeng CHEN

doi:10.16305/j.1007-1334.2022.2111064

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Study on treatment of severe acute pancreatitis with Dachengqi Decoction through inhibition of HMGB1 and NLRP3 inflammasomes

更新时间：2022-09-30

- Study on treatment of severe acute pancreatitis with Dachengqi Decoction through inhibition of HMGB1 and NLRP3 inflammasomes
- Shanghai Journal of Traditional Chinese Medicine Vol. 56, Issue 9, Pages: 70-75(2022)
- 作者机构：
  
  1.上海中医药大学附属普陀医院普外科（上海 200062）
- 作者简介：
- 基金信息：
- DOI：10.16305/j.1007-1334.2022.2111064
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李劼,程卓安,马骄阳,等.大承气汤通过抑制HMGB1及NLRP3炎症小体治疗重症急性胰腺炎的研究[J].上海中医药杂志,2022,56(9):70-75.

LI Jie,CHENG Zhuoan,MA Jiaoyang,et al.Study on treatment of severe acute pancreatitis with Dachengqi Decoction through inhibition of HMGB1 and NLRP3 inflammasomes[J].Shanghai Journal of Traditional Chinese Medicine,2022,56(9):70-75.
李劼,程卓安,马骄阳,等.大承气汤通过抑制HMGB1及NLRP3炎症小体治疗重症急性胰腺炎的研究[J].上海中医药杂志,2022,56(9):70-75. DOI： 10.16305/j.1007-1334.2022.2111064.

LI Jie,CHENG Zhuoan,MA Jiaoyang,et al.Study on treatment of severe acute pancreatitis with Dachengqi Decoction through inhibition of HMGB1 and NLRP3 inflammasomes[J].Shanghai Journal of Traditional Chinese Medicine,2022,56(9):70-75. DOI： 10.16305/j.1007-1334.2022.2111064.

摘要

目的,2,探讨大承气汤对重症急性胰腺炎（SAP）模型小鼠高迁移率族蛋白B1（HMGB1）、NOD样受体蛋白3（NLRP3）炎症小体表达的影响。,方法,2,雄性C57BL/6 小鼠随机分为对照组、模型组，以及大承气汤低、中、高剂量组，每组6只。对照组腹腔注射0.9% NaCl注射液，其余小鼠腹腔注射雨蛙素、脂多糖诱导SAP模型，大承气汤低、中、高剂量组分别在造模成功后0 h、8 h、16 h给予大承气汤灌胃。造模18 h后，试剂盒检测小鼠血清髓过氧化物酶（MPO）、乳酸脱氢酶（LDH）、胰蛋白酶水平，ELISA法检测血清HMGB1、白介素-1β（IL-1β）、白介素-18（IL-18）水平，HE染色后光镜下观察胰腺组织形态学变化，免疫组化、Western blot法检测胰腺组织中嘌呤能离子通道型受体7（P2X7）、NLRP3、凋亡相关的斑点样蛋白（ASC）、天冬氨酸特异性半胱氨酸蛋白酶1（Caspase-1）表达水平。,结果,2,①与对照组比较，模型组小鼠血清HMGB1、IL-1β、IL-18、胰蛋白酶、LDH、MPO水平升高（,P,<,0.05）；与模型组比较，大承气汤低剂量组血清胰蛋白酶水平降低（,P,<,0.05），大承气汤中、高剂量组血清HMGB1、IL-1β、IL-18、胰蛋白酶、LDH、MPO水平降低（,P,<,0.05）。②模型组小鼠胰腺组织出现水肿、出血和炎性坏死，大承气汤可以减轻上述损伤，保护胰腺组织。③大承气汤中、高剂量组能明显抑制SAP小鼠NLRP3炎症小体上游P2X7及其组分NLRP3、ASC和Caspase-1的表达（,P,<,0.05）。,结论,2,大承气汤可以有效抑制HMGB1表达及NLRP3炎症小体活化，抑制炎性因子生成，从而改善SAP模型小鼠胰腺功能。

Abstract

Objective,2,To investigate the effect of Dachengqi Decoction on the expression of high mobility group protein B1 （HMGB1） and NOD-like receptor protein 3 （NLRP3） inflammasomes in mice with severe acute pancreatitis （SAP） model.,Methods,2,Male C57BL/6 mice were randomly divided into a control group， a model group， and low， medium and high dose groups of Dachengqi Decoction， with 6 mice in each group. The control group was given intraperitoneal injection of 0.9% NaCl solution， and the rest mice were given intraperitoneal injection of caerulein and lipopolysaccharide to induce SAP model. Dachengqi Decoction was given to the low， medium and high dose groups by gavage at 0 h， 8 h and 16 h after the successful establishment of the model， respectively. After 18 h of modeling， the serum myeloperoxidase （MPO）， lactate dehydrogenase （LDH） and trypsin levels were detected by the kit. Serum levels of HMGB1， interleukin-1β （IL-1β） and interleukin-18 （IL-18） were detected by ELISA. After HE staining， the morphological changes of pancreatic tissue were observed under light microscope. Immunohistochemistry and Western blot analysis were used to detect the expression levels of P2X purinoceptor 7 （P2X7）， NLRP3， apoptosis-associated speck-like protein （ASC） and aspartate-specific cysteine protease 1 （Caspase-1） in pancreatic tissue.,Results,2,①The serum levels of HMGB1， IL-1β， IL-18， trypsin， LDH and MPO in the model group were higher than those in the control group （,P,<,0.05）； Compared with the model group， the Dachengqi Decoction low dose group had lower level of serum trypsin （,P,<,0.05）， and the medium and high dose groups had lower serum levels of HMGB1， IL-1β， IL-18， trypsin， LDH and MPO （,P,<,0.05）. ②There were edema， hemorrhage and inflammatory necrosis in the pancreatic tissue of mice in the model group. Dachengqi Decoction could alleviate the above injuries and protect the pancreatic tissue. ③The Dachengqi Decoction medium and high dose groups could significantly inhibit the expression of upstream P2X7 and its components NLRP3， ASC and Caspase-1 of NLRP3 inflammasomes in SAP mice,（,P,<,0.05）.,Conclusion,2,Dachengqi Decoction can effectively inhibit the expression of HMGB1， the activation of NLRP3 inflammasomes and the production of inflammatory factors， thus improving the pancreatic function of SAP model mice.

关键词

重症急性胰腺炎大承气汤高迁移率族蛋白B1NOD样受体蛋白3小鼠模型经典名方

Keywords

severe acute pancreatitisDachengqi Decoctionhigh mobility group protein B1NLRP3mice modelclassical representative famous prescription

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