1.上海中医药大学附属曙光医院肝病研究所(上海 201203)
2.肝肾疾病病证教育部重点实验室(上海 201203)
3.上海市中医临床重点实验室(上海 201203)
侯天禄,男,硕士研究生,主治医师,主要从事中西医结合治疗肝脏疾病研究工作
成扬,研究员,博士研究生导师; E-mail: drchengyang@126.com
扫 描 看 全 文
侯天禄,陈天阳,王浩艺,等.疏肝化痰降脂方减轻非酒精性脂肪性肝病小鼠炎症损伤的作用及机制研究[J].上海中医药杂志,2023,57(2):59-65.
HOU Tianlu,CHEN Tianyang,WANG Haoyi,et al.Effects and mechanism of Shugan Huatan Jiangzhi Decoction on reducing inflammatory injury in mice with non⁃alcoholic fatty liver disease[J].Shanghai Journal of Traditional Chinese Medicine,2023,57(2):59-65.
侯天禄,陈天阳,王浩艺,等.疏肝化痰降脂方减轻非酒精性脂肪性肝病小鼠炎症损伤的作用及机制研究[J].上海中医药杂志,2023,57(2):59-65. DOI: 10.16305/j.1007-1334.2023.2208059.
HOU Tianlu,CHEN Tianyang,WANG Haoyi,et al.Effects and mechanism of Shugan Huatan Jiangzhi Decoction on reducing inflammatory injury in mice with non⁃alcoholic fatty liver disease[J].Shanghai Journal of Traditional Chinese Medicine,2023,57(2):59-65. DOI: 10.16305/j.1007-1334.2023.2208059.
目的,2,观察疏肝化痰降脂方对非酒精性脂肪性肝病(NAFLD)小鼠炎症损伤的作用及机制,以期为疏肝化痰降脂方的临床应用提供实验依据。,方法,2,50只C57BL/6雄性小鼠被随机分为5组:正常对照组(质量分数为0.9%的氯化钠溶液)、模型组(质量分数为0.9%的氯化钠溶液)、疏肝化痰降脂方低剂量组(8.32 g/kg)、疏肝化痰降脂方组中剂量组(16.65 g/kg)和疏肝化痰降脂方高剂量组(33.29 g/kg),每组10只。采用高脂饲料喂养方式构建NAFLD小鼠动物模型,于给药后12周末处死。观察小鼠肝脏组织病理学形态变化;检测小鼠血清中炎症因子白介素-1β(IL-1β)、白介素-6(IL-6)及肿瘤坏死因子-α(TNF-α)的表达水平;检测小鼠肝脏组织中Toll样受体4(TLR4)、髓样分化因子88(MyD88)、核因子-κB p65(NF-κB p65)的蛋白与mRNA表达水平。,结果,2,与正常对照组比较,模型组小鼠肝组织炎症损伤严重,疏肝化痰降脂方各剂量组干预后,小鼠肝脏组织损伤程度明显减轻,炎性病灶显著减少。与正常对照组比较,模型组小鼠血清IL-1β、IL-6和TNF-α的表达水平及肝脏组织中MyD88、p-NF-κB p65,蛋白与,TLR4,、,MyD88,及,NF,-,κB p65, mRNA表达均显著升高(,P,<,0.05);与模型组比较,疏肝化痰降脂方各剂量组小鼠血清IL-1β、IL-6和TNF-α 水平及肝脏组织中TLR4、MyD88、p-NF-κB p65 蛋白与,TLR4、MyD88,及,NF,-,κB p65, mRNA表达均显著降低(,P,<,0.05)。,结论,2,疏肝化痰降脂方可能是通过抑制TLR4/MyD88/NF-κB信号通路激活减轻NAFLD小鼠炎症损伤。
Objective,2,To observe the effects and mechanism of Shugan Huatan Jiangzhi Decoction (SHJD) on inflammatory injury in mice with non-alcoholic fatty liver disease (NAFLD) in order to provide experimental basis for the SHJD clinical application.,Methods,2,Fifty C57BL/6 male mice were randomly divided into 5 groups: normal control group (normal saline), model group (normal saline), low-dose SHJD group (8.32 g/kg), medium-dose SHJD group (16.65 g/kg) and high-dose SHJD group (33.29 g/kg), with 10 mice in each group. The NAFLD mouse model was constructed by feeding with high-fat diet, and sacrificed at 12 weeks after administration. The histopathological morphological changes of the mouse liver were observed; the expression levels of inflammatory factors including interleukin-1β (IL-1β), IL-6 and tumor necrosis factor-α (TNF-α) were detected in the serum of the mice in each group; the protein and mRNA expressions of Toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88) and nuclear factor kappa B p65 (NF-κB p65) in mouse liver were detected.,Results,2,Compared with the normal control group, the liver tissue of the mice in the model group was severely damaged by inflammation. After the intervention of different SHJD doses, the degree of liver tissue damage and the inflammatory lesions were significantly reduced in the mice. Compared with the normal control group, the expression levels of serum IL-1β, IL-6 and TNF-α and the expressions of TLR4, MyD88, p-NF-κB p65 protein and ,TLR4,, ,MyD88, and ,NF,-,κB p65, mRNA in the liver tissue of the mice in the model group were significantly increased (,P,<,0.05); Compared with the model group, the serum levels of IL-1β, IL-6 and TNF-α and the expression of TLR4, MyD88, p-NF-κB p65 protein and ,TLR4,, ,MyD88, and ,NF,-,κB p65, mRNA in the liver tissue of the mice treated with SHJD were significantly decreased (,P,<,0.05).,Conclusion,2,SHJD may reduce the inflammatory injury in NAFLD mice by inhibiting the activation of TLR4/MyD88/NF-κB signaling pathway.
非酒精性脂肪性肝病疏肝化痰降脂方炎症反应小鼠模型中药研究
non-alcoholic fatty liver diseaseShugan Huatan Jiangzhi Decoctioninflammatory responsemouse modeltraditional Chinese herbal medicine research
COTTER T G, RINELLA M. Nonalcoholic fatty liver disease 2020: the state of the disease[J]. Gastroenterology, 2020, 158(7): 1851-1864.
CHEN K, MA J, JIA X, et al. Advancing the understanding of NAFLD to hepatocellular carcinoma development: From experimental models to humans[J]. Biochim Biophys Acta Rev Cancer, 2019, 1871(1): 117-125.
YOUNOSSI Z, TACKE F, ARRESE M, et al. Global perspectives on nonalcoholic fatty liver disease and nonalcoholic steatohepatitis[J]. Hepatology, 2019, 69(6): 2672-2682.
KUSMINSKI C M, BICKEL P E, SCHERER P E. Targeting adipose tissue in the treatment of obesity-associated diabetes[J]. Nat Rev Drug Discov, 2016, 15(9): 639-660.
CARR R M, ORANU A, KHUNGAR V. Nonalcoholic fatty liver disease: pathophysiology and management[J]. Gastroenterol Clin North Am, 2016, 45(4): 639-652.
TAO H C, CHEN K X, WANG X, et al. CD47 deficiency in mice exacerbates chronic fatty diet-induced steatohepatitis through its role in regulating hepatic inflammation and lipid metabolism[J]. Front Immunol, 2020, 11: 148.
YOUNOSSI Z M. Non-alcoholic fatty liver disease - A global public health perspective[J]. J Hepatol, 2019, 70(3): 531-544.
VIDYA M K, KUMAR V G, SEJIAN V, et al. Toll-like receptors: significance, ligands, signaling pathways, and functions in mammals[J]. Int Rev Immunol, 2018, 37(1): 20-36.
POMYTKIN I A, CLINE B H, ANTHONY D C, et al. Endotoxaemia resulting from decreased serotonin tranporter (5-HTT) function: a reciprocal risk factor for depression and insulin resistance?[J]. Behav Brain Res, 2015, 276: 111-117.
DASU M R, RAMIREZ S, ISSEROFF R R. Toll-like receptors and diabetes: a therapeutic perspective[J]. Clin Sci (Lond), 2012, 122(5): 203-214.
FARRELL G C, VAN ROOYEN D, GAN L, et al. NASH is an inflammatory disorder: pathogenic, prognostic and therapeutic implications[J]. Gut Liver, 2012, 6(2): 149-171.
CHEN W, WANG X, HUANG L I, et al. Hepcidin in non-alcoholic fatty liver disease regulated by the TLR4/NF-κB signaling pathway[J]. Exp Ther Med, 2016, 11(1): 73-76.
白纪红,梁志清,赵日红,等. 青蒿琥酯对非酒精性脂肪肝小鼠肝脏TLR4及MyD88表达的影响[J]. 安徽医科大学学报,2017, 52(10): 1468-1471.
陈天阳,成扬. 成扬运用升降散合小柴胡汤治疗非酒精性脂肪性肝病合并高脂血症经验探析[J]. 中西医结合肝病杂志,2017, 27(6): 378-380.
YOUNOSSI Z M, KOENIG A B, ABDELATIF D, et al. Global epidemiology of nonalcoholic fatty liver disease-Meta-analytic assessment of prevalence, incidence, and outcomes[J]. Hepatology, 2016, 64(1): 73-84.
YOUNOSSI Z, ANSTEE Q M, MARIETTI M, et al. Global burden of NAFLD and NASH: trends, predictions, risk factors and prevention[J]. Nat Rev Gastroenterol Hepatol, 2018, 15(1): 11-20.
DE LEDINGHEN V, RATZIU V, CAUSSE X, et al. Diagnostic and predictive factors of significant liver fibrosis and minimal lesions in patients with persistent unexplained elevated transaminases. A prospective multicenter study[J]. J Hepatol, 2006, 45(4): 592-599.
LI Y, ZHENG R, LI J, et al. Association between triglyceride glucose-body mass index and non-alcoholic fatty liver disease in the non-obese Chinese population with normal blood lipid levels: a secondary analysis based on a prospective cohort study[J]. Lipids Health Dis, 2020, 19(1): 229.
MUSSO G, CASSADER M, GAMBINO R. Non-alcoholic steatohepatitis: emerging molecular targets and therapeutic strategies[J]. Nat Rev Drug Discov, 2016, 15(4): 249-274.
VILAR-GOMEZ E, MARTINEZ-PEREZ Y, CALZADILLA-BERTOT L, et al. Weight loss through lifestyle modification significantly reduces features of nonalcoholic steatohepatitis[J]. Gastroenterology, 2015, 149(2): 367-378.
刘思伽,陈潇凡,胡必成,等. 非酒精性脂肪肝病的发病机制及治疗研究进展[J]. 湖北中医药大学学报, 2019, 21(2): 126-129.
刘梦玲,沈红艺,李中平. 中医药防治非酒精性脂肪性肝病的研究进展[J]. 中西医结合肝病杂志,2019, 29(1): 85-88.
MRIDHA A R, WREE A, ROBERTSON A A B, et al. NLRP3 inflammasome blockade reduces liver inflammation and fibrosis in experimental NASH in mice[J]. J Hepatol, 2017, 66(5): 1037-1046.
FANG C, CAI X, HAYASHI S, et al. Caffeine-stimulated muscle IL-6 mediates alleviation of non-alcoholic fatty liver disease[J]. Biochim Biophys Acta Mol Cell Biol Lipids, 2019, 1864(3): 271-280.
WANG L, JIA Z, WANG B, et al. Berberine inhibits liver damage in rats with non-alcoholic fatty liver disease by regulating TLR4/MyD88/NF-κB pathway[J]. Turk J Gastroenterol, 2020, 31(12): 902-909.
WANG Z, CHENG Z X, ABRAMS S T, et al. Extracellular histones stimulate collagen expression in vitro and promote liver fibrogenesis in a mouse model via the TLR4-MyD88 signaling pathway[J]. World J Gastroenterol, 2020, 26(47): 7513-7527.
潘炟,穆标. 中药治疗非酒精性脂肪性肝病研究进展[J]. 中国处方药,2020, 18(12): 18-20.
马威,杨家耀,安柳,等. 附子理中汤减轻非酒精性脂肪肝大鼠炎症损伤的机制研究[J]. 中国病理生理杂志,2020, 36(12): 2258-2263.
黄海英,彭新君,彭延古. 僵蚕的现代研究进展[J]. 湖南中医学院学报,2003, 23(4): 62-64.
黄娟,张庆莲,皮凤娟,等. 大黄的药理作用研究进展[J]. 中国医院用药评价与分析,2014, 14(3): 282-284.
麦静愔. 姜黄素对大鼠非酒精性脂肪肝的干预作用[J]. 中国中西医结合消化杂志,2011, 19(4): 239-242.
马玲玲,孙燕. 中药黄芩药理作用的研究进展[J]. 沈阳医学院学报,2016, 18(2): 115-117.
李琰. 柴胡药理作用的研究进展[J]. 河北医学,2010, 16(5): 633-635.
0
浏览量
185
下载量
1
CSCD
0
CNKI被引量
关联资源
相关文章
相关作者
相关机构