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盐酸青藤碱介导Hedgehog信号通路治疗小鼠溃疡性结肠炎分子机制的研究

徐峰 徐琳霞 刘伟 王珂珂 陈彩凤 谢丽 柯希权

徐峰, 徐琳霞, 刘伟, 王珂珂, 陈彩凤, 谢丽, 柯希权. 盐酸青藤碱介导Hedgehog信号通路治疗小鼠溃疡性结肠炎分子机制的研究[J]. 中华全科医学, 2022, 20(10): 1654-1657. doi: 10.16766/j.cnki.issn.1674-4152.002671
引用本文: 徐峰, 徐琳霞, 刘伟, 王珂珂, 陈彩凤, 谢丽, 柯希权. 盐酸青藤碱介导Hedgehog信号通路治疗小鼠溃疡性结肠炎分子机制的研究[J]. 中华全科医学, 2022, 20(10): 1654-1657. doi: 10.16766/j.cnki.issn.1674-4152.002671
XU Feng, XU Lin-xia, LIU Wei, WANG Ke-ke, CHEN Cai-feng, Xie Li, KE Xi-quan. The molecular mechanism of sinomenine hydrochloride treat ulcerative colitis through Hedgehog signalling pathway in mice[J]. Chinese Journal of General Practice, 2022, 20(10): 1654-1657. doi: 10.16766/j.cnki.issn.1674-4152.002671
Citation: XU Feng, XU Lin-xia, LIU Wei, WANG Ke-ke, CHEN Cai-feng, Xie Li, KE Xi-quan. The molecular mechanism of sinomenine hydrochloride treat ulcerative colitis through Hedgehog signalling pathway in mice[J]. Chinese Journal of General Practice, 2022, 20(10): 1654-1657. doi: 10.16766/j.cnki.issn.1674-4152.002671

盐酸青藤碱介导Hedgehog信号通路治疗小鼠溃疡性结肠炎分子机制的研究

doi: 10.16766/j.cnki.issn.1674-4152.002671
基金项目: 

安徽省教育厅2018年度高校优秀青年骨干人才国内外访学研修项目 gxgwfx2018052

详细信息
    通讯作者:

    柯希权, E-mail: kexq2006@sina.com

  • 中图分类号: R574.62  R-332

The molecular mechanism of sinomenine hydrochloride treat ulcerative colitis through Hedgehog signalling pathway in mice

  • 摘要:   目的  研究盐酸青藤碱(SH)对小鼠溃疡性结肠炎(UC)的保护作用及可能机制。   方法  将24只小鼠采用随机数字表法分为正常组、模型组、SH低、高剂量组(SH 20 mg/kg、60 mg/kg)4组,每组6只;记录疾病活动指数(DAI)和结肠组织病理学评分,检测Shh mRNA及相关蛋白和细胞因子的表达。   结果  与正常组相比,模型组DAI评分[(3.44±0.27)分vs. 0分, P<0.001]升高,组织病理学评分升高[(7.67±0.52)分vs. 0分,P<0.001],Shh mRNA降低(P<0.05),Shh、Smo、Ptch1、Gli1蛋白表达水平降低(均P<0.01),TNF-α、IL-1β、IL-6升高(均P<0.001);与模型组相比, SH低、高剂量组DAI评分[(2.50±0.18)分、(1.89±0.17)分vs. (3.44±0.27)分, P < 0.001]降低, 组织病理学评分降低[(5.17±0.75)分、(3.33±0.52)分vs. (7.67±0.52)分, P < 0.001],Shh、Smo、Ptch1、Gli1蛋白升高(均P<0.001),TNF-α、IL-1β、IL-6降低(均P<0.01)。   结论  SH可治疗小鼠UC,其机制可能是SH上调了Hedgehog信号通路活性,从而降低了TNF-α、IL-1β、IL-6含量。

     

  • 图  1  各组小鼠体重下降百分比及DAI评分比较

    注:A为各组小鼠体重相当于初始值百分比;B为各组小鼠DAI评分。与同时间点正常组比较,aP<0.001;与同时间点模型组比较,bP<0.001;与SH低剂量组比较,cP<0.001。

    Figure  1.  Comparison of weight loss percentage and DAI score of mice in each group

    图  2  各组小鼠HE染色情况(×100)

    注:A为正常组,B为模型组,C为SH低剂量组,D为SH高剂量组。

    Figure  2.  HE staining of mice in each group(×100)

    图  3  各组小鼠结肠中Hedgehog通路相关蛋白表达情况

    Figure  3.  Expression of Hedgehog signaling pathway related proteins in colon of mice in each group

    表  1  各组小鼠结肠组织内Hedgehog信号通路Shh、Smo、Ptch1、Gli1蛋白表达水平比较(x±s)

    Table  1.   Comparison of the protein expression levels of Shh, Smo, Ptch1 and Gli1 of Hedgehog signaling pathway in colon tissue of mice in each group(x±s)

    组别 只数 Shh Smo Ptch1 Gli1
    正常组 6 1.00±0.00 1.00±0.00 1.00±0.00 1.00±0.00
    模型组 6 0.77±0.08a 0.80±0.09a 0.73±0.09a 0.74±0.10a
    SH低剂量组 6 1.44±0.10ab 1.35±0.15ab 1.42±0.13ab 1.56±0.16ab
    SH高剂量组 6 1.83±0.20abc 1.62±0.22abc 1.81±0.09abc 2.05±0.20abc
    F 94.771 51.484 132.684 97.811
    P <0.001 <0.001 <0.001 <0.001
    注:与正常组比较,aP < 0.05;与模型组比较,bP < 0.05;与SH低剂量组比较,cP < 0.05。
    下载: 导出CSV

    表  2  各组小鼠血清中细胞因子TNF-α、IL-1β、IL-6表达水平比较(x±s,pg/mL)

    Table  2.   Comparison of cytokine TNF-α, IL-1β, IL-6 expression levels in serum of mice in each group (x±s, pg/mL)

    1组别 只数 TNF-α IL-1β IL-6
    正常组 6 164.61±29.09 21.95±1.56 32.78±6.84
    模型组 6 718.53±81.81a 51.62±2.80a 444.07±67.77a
    SH低剂量组 6 544.72±90.03ab 34.10±2.90ab 345.43±43.40ab
    SH高剂量组 6 434.11±71.75abc 29.44±3.70abc 236.11±29.35abc
    F 62.258 72.606 101.150
    P <0.001 <0.001 <0.001
    注:与正常组比较,aP<0.001;与模型组比较,bP<0.01;与SH低剂量组比较,cP<0.05。
    下载: 导出CSV
  • [1] FLYNN S, EISENSTEIN S. Inflammatory bowel disease presentation and diagnosis[J]. Surg Clin North Am, 2019, 99(6): 1051-1062. doi: 10.1016/j.suc.2019.08.001
    [2] 徐峰, 柯希权. 溃疡性结肠炎与肠道微生物关系研究进展[J]. 胃肠病学和肝病学杂志, 2021, 30(9): 969-971. doi: 10.3969/j.issn.1006-5709.2021.09.003

    XU F, KE X Q. Progress of ulcerative colitis and intestinal microorganisms[J]. Chinese Journal of Gastroenterology and Hepatology, 2021, 30(9): 969-971. doi: 10.3969/j.issn.1006-5709.2021.09.003
    [3] NG S C, SHI H Y, HAMIDI N, et al. Worldwide incidence and prevalence of inflammatory bowel disease in the 21st century: A systematic review of population-based studies[J]. Lancet, 2017, 390(10114): 2769-2778. doi: 10.1016/S0140-6736(17)32448-0
    [4] 吴开春, 梁洁, 冉志华, 等. 炎症性肠病诊断与治疗的共识意见(2018年·北京)[J]. 中国实用内科杂志, 2018, 38(9): 796-813. doi: 10.19538/j.nk2018090106

    WU K C, LIANG J, RAN Z H, et al. Chinese consensus on diagnosis and treatment of inflammatory bowel disease (Beijing, 2018)[J]. Chinese Journal of Practical Internal Medicine, 2018, 38(9): 796-813. doi: 10.19538/j.nk2018090106
    [5] FU Y F, LI L, FANG P, et al. Sinomenine ' s protective role and mechanism in stress load-induced heart failure[J]. J Pharm Pharmacol, 2020, 72(2): 209-217. doi: 10.1111/jphp.13181
    [6] SINGH D, AGRAWAL A, SINGAL C M S, et al. Sinomenine inhibits amyloid beta-induced astrocyte activation and protects neurons against indirect toxicity[J]. Mol Brain, 2020, 13(1): 30. doi: 10.1186/s13041-020-00569-6
    [7] GAO L N, ZHONG B, WANG Y. Mechanism underlying antitumor effects of sinomenine[J]. Chin J Integr Med, 2019, 25(11): 873-878. doi: 10.1007/s11655-019-3151-2
    [8] ZHOU Y, LIU H Y, SONG J, et al. Sinomenine alleviates dextran sulfate sodium-induced colitis via the Nrf2/NQO-1 signaling pathway[J]. Mol Med Rep, 2018, 18(4): 3691-3698.
    [9] ABRAHAM B P, QUIGLEY E M M. Probiotics in inflammatory bowel disease[J]. Gastroenterol Clin North Am, 2017, 46(4): 769-782. doi: 10.1016/j.gtc.2017.08.003
    [10] VEENSTRA J P, VEMU B, TOCMO R, et al. Pharmacokinetic analysis of carnosic acid and carnosol in standardized rosemary extract and the effect on the disease activity index of DSS-induced colitis[J]. Nutrients, 2021, 13(3): 773-789. doi: 10.3390/nu13030773
    [11] KOJIMA F, SEKIYA H, HIOKI Y, et al. Facilitation of colonic T cell immune responses is associated with an exacerbation of dextran sodium sulfate-induced colitis in mice lacking microsomal prostaglandin E synthase-1[J]. Inflamm Regen, 2022, 42(1): 1. doi: 10.1186/s41232-021-00188-1
    [12] KUCHARZIK T. Living guideline on ulcerative colitis[J]. Chirurg, 2022, 93(3): 261-265. doi: 10.1007/s00104-022-01594-y
    [13] WALTON K D, GUMUCIO D L. Hedgehog signaling in intestinal development and homeostasis[J]. Annu Rev Physiol, 2021, 83: 359-380. doi: 10.1146/annurev-physiol-031620-094324
    [14] BUONGUSTO F, BERNARDAZZI C, YOSHIMOTO A N, et al. Disruption of the Hedgehog signaling pathway in inflammatory bowel disease fosters chronic intestinal inflammation[J]. Clin Exp Med, 2017, 17(3): 351-369. doi: 10.1007/s10238-016-0434-1
    [15] EICHELE D D, KHARBANDA K K. Dextran sodium sulfate colitis murine model: An indispensable tool for advancing our understanding of inflammatory bowel diseases pathogenesis[J]. World J Gastroenterol, 2017, 23(33): 6016-6029. doi: 10.3748/wjg.v23.i33.6016
    [16] NEURATH M F, CHIRIAC M T. Targeting immune cell wiring in ulcerative colitis[J]. Immunity, 2019, 51(5): 791-793. doi: 10.1016/j.immuni.2019.10.011
    [17] 江海燕, 王新月, 王建云, 等. 解毒活血灌肠方联合中药口服治疗溃疡性结肠炎患者的临床研究[J]. 中华全科医学, 2021, 19(11): 1925-1928, 1955. doi: 10.16766/j.cnki.issn.1674-4152.002202

    JIANG H Y, WANG X Y, WANG J Y, et al. Clinical study of Jiedu Huoxue Decoction enema combined with oral Chinese medicine in patients with ulcerative colitis[J]. Chinese Journal of General Practice, 2021, 19(11): 1925-1928, 1955. doi: 10.16766/j.cnki.issn.1674-4152.002202
    [18] LIU W W, ZHANG Y J, ZHU W N, et al. Sinomenine inhibits the progression of rheumatoid arthritis by regulating the secretion of inflammatory cytokines and monocyte/macrophage subsets[J]. Front Immunol, 2018, 9: 2228. doi: 10.3389/fimmu.2018.02228
    [19] GAO T L, SHI T S, WIESENFELD-HALLIN Z, et al. Sinomenine facilitates the efficacy of gabapentin or ligustrazine hydrochloride in animal models of neuropathic pain[J]. Eur J Pharmacol, 2019, 854: 101-108. doi: 10.1016/j.ejphar.2019.03.061
    [20] HELAL M G, ABD ELHAMEED A G. Graviola mitigates acetic acid-induced ulcerative colitis in rats: Insight on apoptosis and Wnt/Hh signaling crosstalk[J]. Environ Sci Pollut Res Int, 2021, 28(23): 29615-29628. doi: 10.1007/s11356-021-12716-0
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  • 收稿日期:  2022-03-30
  • 网络出版日期:  2022-11-30

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