LI Jiaolong,ZHOU Zhenhua.Study on effects of Rougan Formula on IL⁃22 secretion and IL⁃22R1 expression in liver of mice with liver fibrosis[J].Academic Journal of Shanghai University of Traditional Chinese Medicine,2022,36(05):69-76.
LI Jiaolong,ZHOU Zhenhua.Study on effects of Rougan Formula on IL⁃22 secretion and IL⁃22R1 expression in liver of mice with liver fibrosis[J].Academic Journal of Shanghai University of Traditional Chinese Medicine,2022,36(05):69-76. DOI: 10.16306/j.1008-861x.2022.05.012.
Study on effects of Rougan Formula on IL⁃22 secretion and IL⁃22R1 expression in liver of mice with liver fibrosis
Objective: To study the effects of Rougan Formula on interleukin-22 (IL-22) secretion and IL-22 receptor 1 (IL-22R1) expression in the liver of concanavalin A (ConA) combined with 3,5-diethoxy carbonyl-1,4-dihydro-2,4,6-trimethylpyridine (DDC) induced liver fibrosis mice, and to explore the mechanism of Rougan Formula against liver fibrosis.,Methods,2,Sixty mice were randomly divided into control group, model group and Rougan Formula group, with 20 mice in each group. The mice in the model group and Rougan Formula group were injected with ConA through the tail vein once a week and fed with DDC diet. The mice in the control group were injected with equal volume of 0.9% NaCl solution through the tail vein and fed with normal diet. The mice in Rougan Formula group were given Rougan Formula granules by gavage (8.5 g/kg) once a day. The mice in control and model group were given equal volume of 0.9% NaCl solution by gavage. The Drug intervention lasted for 10 weeks. The mice were killed after 10 weeks, liver function, secretion of IL-22 and expression of IL-22R1 in liver were observed.,Results,2,①Compared with the control group, the expression of, IL,-,22,,IL,-,22R1,, ,IL,-,10R2, and ,STAT3, mRNA in the liver of mice in the model group and Rougan Formula group significantly increased (,P,<,0.01,,P,<,0.001). Compared with the model group, the expression of ,IL,-,22, and ,IL,-,10R2, mRNA in the liver of mice in the Rougan Formula group significantly increased (,P,<,0.001). ②Compared with the control group, the expression of ,IL,-,22R1, mRNA on the surface of hepatic stellate cells (HSCs) in the model group significantly increased (,P,<,0.05), the expression of ,STAT3, mRNA in HSCs significantly increased (,P,<,0.05), the expression of, IL,-,22R1, and ,IL,-,10R2, mRNA on the surface of HSCs in the Rougan Formula group significantly increased (,P,<,0.05,,P,<,0.001), and the expression of ,STAT3, mRNA in HSCs in the Rougan Formula group significantly increased (,P,<,0.001). Compared with the model group, the expression of ,IL,-,22R1, mRNA on the surface of HSCs and ,STAT3, mRNA in HSCs in the Rougan Formula group significantly increased (,P,<,0.01,,P,<,0.001). ③Compared with the control group, the number of Th22 cells in the model group and Rougan Formula group significantly increased (,P,<,0.001). Compared with the model group, the number of Th22 cells in the Rougan Formula group significantly increased (,P,<,0.01).,Conclusion,2,Rougan Formula can increase the secretion of IL-22 in the liver and the expression of IL-22R1 on the surface of HSCs, so as to play the role of anti-hepatic fibrosis.
关键词
柔肝方肝纤维化IL-22IL-22R1
Keywords
Rougan Formulahepatic fibrosisIL-22IL-22R1
references
PAROLA M,PINZANI M. Liver fibrosis: Pathophysiology,pathogenetic targets and clinical issues[J]. Mol Aspects Med,2019, 65: 37-55.
TSUCHIDA T,FRIEDMAN S L. Mechanisms of hepatic stellate cell activation[J]. Nat Rev Gastroenterol Hepatol, 2017, 14(7): 397-411.
CHEN Y,FAN Y,GUO D Y,et al. Study on the relationship between hepatic fibrosis and epithelial-mesenchymal transition in intrahepatic cells[J]. Biomed Pharmacother, 2020, 129: 110413.
KISSELEVA T,BRENNER D. Molecular and cellular mechanisms of liver fibrosis and its regression[J]. Nat Rev Gastroenterol Hepatol, 2021, 18(3): 151-166.
KONG D, ZHANG Z, CHEN L, et al. Curcumin blunts epithelial-mesenchymal transition of hepatocytes to alleviate hepatic fibrosis through regulating oxidative stress and autophagy[J]. Redox Biol,2020, 36: 101600.
RODERFELD M. Matrix metalloproteinase functions in hepatic injury and fibrosis[J]. Matrix Biol, 2018, 68-69: 452-462.
ZONG Z, LIU J, WANG N, et al. Nicotinamide mononucleotide inhibits hepatic stellate cell activation to prevent liver fibrosis via promoting PGE2 degradation[J]. Free Radic Biol Med, 2021, 162: 571-581.
YANG W,YU T,HUANG X,et al. Intestinal microbiota-derived short-chain fatty acids regulation of immune cell IL-22 production and gut immunity[J]. Nat Commun,2020,11(1):4457.
ZENEWICZ L A, YANCOPOULOS G D, VALENZUELA D M, et al. Interleukin-22 but not interleukin-17 provides protection to hepatocytes during acute liver inflammation[J]. Immunity, 2007, 27(4): 647-659.
MIZOGUCHI A, YANO A, HIMURO H, et al. Clinical importance of IL-22 cascade in IBD[J]. J Gastroenterol, 2018, 53(4): 465-474.
SONNENBERG G F, FOUSER L A, ARTIS D. Border patrol: regulation of immunity,inflammation and tissue homeostasis at barrier surfaces by IL-22[J]. Nat Immunol, 2011, 12(5): 383-390.
EYERICH K,DIMARTINO V,CAVANI A. IL-17 and IL-22 in immunity: Driving protection and pathology[J]. Eur J Immunol, 2017, 47(4): 607-614.
KHAWAR M B, AZAM F, SHEIKH N, et al. How Does Interleukin-22 Mediate Liver Regeneration and Prevent Injury and Fibrosis?[J]. J Immunol Res, 2016, 2016: 2148129.
GAO B,XIANG X. Interleukin-22 from bench to bedside: a promising drug for epithelial repair[J]. Cell Mol Immunol, 2019, 16(7): 666-667.
HWANG S, HE Y, XIANG X, et al. Interleukin-22 Ameliorates Neutrophil-Driven Neutrophil-Driven Nonalcoholic Steatohepatitis Through Multiple Targets[J]. Hepatology, 2020, 72(2): 412-429.
SCHWARZKOPF K,RUSCHENBAUM S, BARAT S,et al. IL-22 and IL-22-Binding Protein Are Associated With Development of and Mortality From Acute-on-Chronic Liver Failure[J]. Hepatol Commun, 2019, 3(3): 392-405.
Characteristics of changes of intrahepatic lymphocyte subsets in mouse with hepatic fibrosis induced by carbon tetrachlorideand dimethylnitrosamine and the regulatory effect of Fuzheng Huayu Formula
Anti⁃fibrosis mechanism of Bushen Rougan Formula inhibiting angiogenesis in mice
Clinical study on Jianpi Rougan Recipe combined with entecavir in the treatment of chronic hepatitis B with hepatic fibrosis
Related Author
No data
Related Institution
Institute of Liver Diseases, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine
Shanghai Key Clinical Laboratory of Traditional Chinese Medicine
Institute of Hepatology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine
Department of Hepatology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine
Department of Hepatology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine