Protective effect of Qingjie Huagong decoction on pancreatic tissue of mice with severe acute pancreatitis by regulating the NOD-like receptor protein 3/Toll-like receptor 4/nuclear factor-kappa B signaling pathway

Minchao FENG; Baijun QIN; Fang LUO; Kai LI; Ning WANG; Guozhong CHEN; Xiping TANG

doi:10.12449/JCH240219

Volume 40 Issue 2

Feb. 2024

Turn off MathJax

Article Contents

Article Navigation > Journal of Clinical Hepatology > 2024 > 40(2): 343-350

PDF( 2916 KB)

Protective effect of Qingjie Huagong decoction on pancreatic tissue of mice with severe acute pancreatitis by regulating the NOD-like receptor protein 3/Toll-like receptor 4/nuclear factor-kappa B signaling pathway

DOI: 10.12449/JCH240219

1.
The First Clinical School of Medicine，Guangxi University of Chinese Medicine，Nanning 530000，China
2.
Department of Gastroenterology，The First Affiliated Hospital of Guangxi University of Chinese Medicine，Nanning 530023，China
3.
Endoscopy Center，Guangxi Medical University Cancer Hospital，Nanning 530021，China

Research funding:

National Natural Science Foundation of China Project (82160890);

General Project of Guangxi Natural Science Foundation (2020GXNSFAA297062);

Guangxi Medical and Healthcare Appropriate Technology Development and Popularization and Application Project (S2019021);

Guangxi University of TCM Graduate Education Innovation Program Project (YCSW2023383)

More Information

Corresponding author: CHEN Guozhong， cheninjp@163.com （ORCID： 0009-0008-8374-5628）
Received Date: 2023-06-02
Accepted Date: 2023-07-24
Published Date: 2024-02-19

Abstract

Abstract

Objective To investigate the therapeutic effect of Qingjie Huagong decoction （QJHGD） on a mouse model of severe acute pancreatitis （SAP） and the mechanism of action of QJHGD against inflammatory response. Methods A total of 36 male C57BL/6J mice were randomly divided into blank group， model group， Western medicine group （ulinastatin）， and low-， middle-， and high-dose QJHGD groups， with 6 mice in each group. All mice except those in the blank group were given 5% sodium taurocholate by retrograde pancreaticobiliary injection to establish a model of SAP. After modeling， the mice in the low-， middle-， and high-dose groups were given QJHGD （1， 2， and 4 g/kg， respectively） by gavage， and those in the Western medicine group were given intraperitoneal injection of ulinastatin （5×10⁴ U/kg）， for 7 days in total. HE staining was used to observe the histopathological changes of the pancreas； ELISA was used to measure the levels of α-amylase， lipase， interleukin-1β （IL-1β）， interleukin-6 （IL-6）， interleukin-8 （IL-8）， interleukin-18 （IL-18）， and tumor necrosis factor-α （TNF-α） in mice； RT-qPCR was used to measure the mRNA expression levels of NOD-like receptor protein3 （NLRP3）， Toll-like receptor 4 （TLR4）， and nuclear factor-kappa B （NF-κB） in pancreatic tissue； immunohistochemistry was used to measure the positive expression rates of NLRP3， TLR4， and NF-κB in pancreatic tissue； Western blot was used to measure the protein expression levels of NLRP3， TLR4， NF-κB， IL-1β， and IL-6. An analysis of variance was used for comparison of continuous data between multiple groups， and the least significant difference t-test was used for further comparison between two groups. Results Compared with the blank group， the model group had diffuse destruction of pancreatic tissue structure， focal dilatation of pancreatic lobular septum， pancreatic acinar atrophy， and massive inflammatory cell infiltration， as well as significant increases in the content of α-amylase， lipase， IL-1β， IL-6， IL-8， IL-18， and TNF-α （all P<0.05）， the mRNA expression levels and positive expression rates of NLRP3， TLR4， and NF-κB （all P<0.05）， and the protein expression levels of NLRP3， TLR4， NF-κB， IL-1β， and IL-6 （all P<0.05）. Compared with the model group， the low-， middle-， and high-dose QJHGD groups and the Western medicine group had slightly tighter and more intact structure of pancreatic tissue， ordered arrangement of pancreatic acinar cells， a small amount of inflammatory cell infiltration， and hemorrhagic foci of pancreatic lobules， as well as significant reductions in the content of α-amylase， lipase， IL-1β， IL-6， IL-8， IL-18， and TNF-α （all P<0.05）， the mRNA expression levels and positive expression rates of NLRP3， TLR4， and NF-κB （all P<0.05）， and the protein expression levels of NLRP3， TLR4， NF-κB， IL-1β， and IL-6 （all P<0.05）. Conclusion QJHGD may exert a protective effect on the pancreatic tissue of SAP mice by inhibiting the activation of NLRP3/TLR4/NF-κB signaling pathway-related proteins， reducing the release of inflammatory mediators， and preventing the enhancement of inflammatory cascade response.
- Pancreatitis,
- NLR Proteins,
- Toll-Like Receptor 4,
- NF-kappa B,
- Qingjie Huagong Decoction,
- Mice， Inbred C57BL

FullText(HTML)

References(21)

References

[1]	IANNUZZI JP, KING JA, LEONG JH, et al. Global incidence of acute pancreatitis is increasing over time: A systematic review and meta-analysis[J]. Gastroenterology, 2022, 162( 1): 122- 134. DOI: 10.1053/j.gastro.2021.09.043.
[2]	TRIKUDANATHAN G, WOLBRINK DRJ, van SANTVOORT HC, et al. Current concepts in severe acute and necrotizing pancreatitis: An evidence-based approach[J]. Gastroenterology, 2019, 156( 7): 1994- 2007. DOI: 10.1053/j.gastro.2019.01.269.
[3]	SZATMARY P, GRAMMATIKOPOULOS T, CAI WH, et al. Acute pancreatitis: Diagnosis and treatment[J]. Drugs, 2022, 82( 12): 1251- 1276. DOI: 10.1007/s40265-022-01766-4.
[4]	de-MADARIA E, BUXBAUM JL, MAISONNEUVE P, et al. Aggressive or moderate fluid resuscitation in acute pancreatitis[J]. N Engl J Med, 2022, 387( 11): 989- 1000. DOI: 10.1056/NEJMoa2202884.
[5]	PENG H, CHEN GZ, FANG LJ, et al. Clearing and resolving and purging method combined high strength training in early stage for severe acute pancreatitis[J]. Liaoning J Tradit Chin Med, 2019, 46( 5): 991- 994. DOI: 10.13192/j.issn.1000-1719.2019.05.032. 彭鸿, 陈国忠, 方丽娇, 等. 清解化攻法合并高强度综合治疗在重症急性胰腺炎早期的作用[J]. 辽宁中医杂志, 2019, 46( 5): 991- 994. DOI: 10.13192/j.issn.1000-1719.2019.05.032.
[6]	YANG CN, LIU LJ, LIU KR, et al. Clinical observation on adjuvant therapy with Qing Jie Hua Gong Fang for hyperlipidemic acute pancreatitis with syndrome of intermingling blood stasis and toxin[J]. Guangxi Med J, 2021, 43( 24): 2928- 2932. DOI: 10.11675/j.issn.0253-4304.2021.24.08. 杨成宁, 刘礼剑, 刘锟荣, 等. 清解化攻方辅助治疗瘀毒互结型高脂血症性急性胰腺炎的临床观察[J]. 广西医学, 2021, 43( 24): 2928- 2932. DOI: 10.11675/j.issn.0253-4304.2021.24.08.
[7]	QIN BJ, TANG XP, YANG X, et al. The biological information and experimental verification of studying on QingJie HuaGong decoction inhibiting inflammatory response of SAP model rats induced by cerulein based on TLR4/NF-‍κB/MYD88 pathway[J]. Chin Pharmacol Bull, 2022, 38( 6): 935- 944. DOI: 10.12360/CPB202109004. 秦百君, 唐曦平, 杨昕, 等. 基于TLR4/NF-κB/MyD88通路探讨清解化攻方抑制雨蛙素诱导重症急性胰腺炎模型大鼠炎症反应的生信分析及实验验证[J]. 中国药理学通报, 2022, 38( 6): 935- 944. DOI: 10.12360/CPB202109004.
[8]	QIN BJ, YANG X, TANG XP, et al. Mechanism of Qingjie Huagong Decoction inhibiting inflammatory response in rats with severe acute pancreatitis based on transcriptome high-throughput sequencing[J]. China J Tradit Chin Med Pharm, 2022, 37( 5): 2941- 2946. 秦百君, 杨昕, 唐曦平, 等. 基于转录组高通量测序探讨清解化攻方抑制重症急性胰腺炎大鼠炎症反应的机制[J]. 中华中医药杂志, 2022, 37( 5): 2941- 2946.
[9]	YANG X, QIN BJ, TANG XP, et al. Study on the protective effect of Qingjiehuajifang on intestinal mucosal barrier in rats with severe acute pancreatitis by regulating HMGB1/TLR9/NF-κB signaling pathway[J]. Lishizhen Med Mater Med Res, 2022, 33( 10): 2346- 2349. 杨昕, 秦百君, 唐曦平, 等. 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[J]. 时珍国医国药, 2022, 33( 10): 2346- 2349.
[10]	ZAAFAR D, KHALIL HMA, RASHEED RA, et al. Hesperetin mitigates sorafenib-induced cardiotoxicity in mice through inhibition of the TLR4/NLRP3 signaling pathway[J]. PLoS One, 2022, 17( 8): e0271631. DOI: 10.1371/journal.pone.0271631.
[11]	ZHANG MJ, YAO WY, QIAO MM, et al. Establishing severe acute pancreatitis model on rats by retrograde injection of sodium taurocholate into biliopancreatic duct through duodenal wall[J]. J Shanghai Jiao Tong Univ Med Sci, 2006, 26( 5): 488- 490. DOI: 10.3969/j.issn.1674-8115.2006.05.014. 张明钧, 姚玮艳, 乔敏敏, 等. 肠壁穿刺逆行胰胆管注射牛黄胆酸钠重症急性胰腺炎造模[J]. 上海交通大学学报(医学版), 2006, 26( 5): 488- 490. DOI: 10.3969/j.issn.1674-8115.2006.05.014.
[12]	LIU RX, QI HY, WANG J, et al. Ulinastatin activates the renin-angiotensin system to ameliorate the pathophysiology of severe acute pancreatitis[J]. J Gastroenterol Hepatol, 2014, 29( 6): 1328- 1337. DOI: 10.1111/jgh.12584.
[13]	SU YR, HONG YP, MEI FC, et al. High-fat diet aggravates the intestinal barrier injury via TLR4-RIP3 pathway in a rat model of severe acute pancreatitis[J]. Mediators Inflamm, 2019, 2019: 2512687. DOI: 10.1155/2019/2512687.
[14]	ZHENG Z, DING YX, QU YX, et al. A narrative review of acute pancreatitis and its diagnosis, pathogenetic mechanism, and management[J]. Ann Transl Med, 2021, 9( 1): 69. DOI: 10.21037/atm-20-4802.
[15]	HE J, YU S, ZHANG J. Value of serum interleukin-6 and tumor necrosis factor-α in early diagnosis of severe acute pancreatitis[J]. J Clin Hepatol, 2023, 39( 7): 1657- 1664. DOI: 10.3969/j.issn.1001-5256.2023.07.020. 何健, 俞隼, 张静. 血清IL-6和TNF-α对重症急性胰腺炎的早期诊断价值分析[J]. 临床肝胆病杂志, 2023, 39( 7): 1657- 1664. DOI: 10.3969/j.issn.1001-5256.2023.07.020.
[16]	QIN BJ, TANG XP, YANG X, et al. Study on the effects of Qingjie huagong decoction on the regulation of intestinal flora and intestinal mucosal barrier in severe acute pancreatitis model rats[J]. China Pharm, 2022, 33( 15): 1825- 1832. DOI: 10.6039/j.issn.1001-0408.2022.15.07. 秦百君, 唐曦平, 杨昕, 等. 清解化攻方调节重症急性胰腺炎模型大鼠肠道菌群及对肠黏膜屏障的影响[J]. 中国药房, 2022, 33( 15): 1825- 1832. DOI: 10.6039/j.issn.1001-0408.2022.15.07.
[17]	LI XY, HE C, LI NS, et al. The interplay between the gut microbiota and NLRP3 activation affects the severity of acute pancreatitis in mice[J]. Gut Microbes, 2020, 11( 6): 1774- 1789. DOI: 10.1080/19490976.2020.1770042.
[18]	SENDLER M, van den BRANDT C, GLAUBITZ J, et al. NLRP3 inflammasome regulates development of systemic inflammatory response and compensatory anti-inflammatory response syndromes in mice with acute pancreatitis[J]. Gastroenterology, 2020, 158( 1): 253- 269. DOI: 10.1053/j.gastro.2019.09.040.
[19]	YE YZ, JIN T, ZHANG X, et al. Meisoindigo protects against focal cerebral ischemia-reperfusion injury by inhibiting NLRP3 inflammasome activation and regulating microglia/macrophage polarization via TLR4/NF-κB signaling pathway[J]. Front Cell Neurosci, 2019, 13: 553. DOI: 10.3389/fncel.2019.00553.
[20]	LI G, WU XJ, YANG L, et al. TLR4-mediated NF-κB signaling pathway mediates HMGB1-induced pancreatic injury in mice with severe acute pancreatitis[J]. Int J Mol Med, 2016, 37( 1): 99- 107. DOI: 10.3892/ijmm.2015.2410.
[21]	HOU CQ, ZHU XL, SHI CY, et al. Iguratimod(T-614) attenuates severe acute pancreatitis by inhibiting the NLRP3 inflammasome and NF-κB pathway[J]. Biomed Pharmacother, 2019, 119: 109455. DOI: 10.1016/j.biopha.2019.109455.

Relative Articles

Supplements(0)

Cited By

Proportional views

Proportional views

通讯作者: 陈斌, bchen63@163.com

1.
沈阳化工大学材料科学与工程学院沈阳 110142

Figures(3) / Tables(4)

Get Citation

PDF

XML

Article Metrics

Article views (153) PDF downloads(29)

Protective effect of Qingjie Huagong decoction on pancreatic tissue of mice with severe acute pancreatitis by regulating the NOD-like receptor protein 3/Toll-like receptor 4/nuclear factor-kappa B signaling pathway

DOI: 10.12449/JCH240219

Abstract

References

Proportional views

Catalog

通讯作者: 陈斌, bchen63@163.com

Article Metrics

Proportional views

Related

Protective effect of Qingjie Huagong decoction on pancreatic tissue of mice with severe acute pancreatitis by regulating the NOD-like receptor protein 3/Toll-like receptor 4/nuclear factor-kappa B signaling pathway

DOI: 10.12449/JCH240219

Abstract

References

Proportional views

Catalog

通讯作者: 陈斌, bchen63@163.com

Article Metrics

Proportional views

Related

About Journal

Submission Guideline

Journal Online

Hepatobiliary College

Guidelines

Export File

Citation

Format

Content