青黛对溃疡性结肠炎小鼠的治疗作用及其治疗机制研究
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摘要
目的探讨中药青黛对葡聚糖硫酸钠诱导的小鼠溃疡性结肠炎的保护作用及其作用机制。方法 60只SPF级雄性C57BL/6小鼠,体重25-30 g,随机分为对照组(CON组),溃疡性结肠炎组(UC组)、柳氮磺胺吡啶阳性对照组(SASP组)、青黛低剂量组(LQD组)、青黛中剂量组(MQD组)和青黛高剂量组(HQD组),每组10只。利用DSS建立UC模型,采用疾病活动指数评分(DAI)、HE染色、ELISA和Western Blot法评估青黛对溃疡性结肠炎的治疗作用。结果 UC组肠粘膜损伤严重,血浆总TNF-α、IL-6、IL-1、IL-10、MDA含量升高,SOD降低,青黛组可以抑制DSS引发的小鼠溃疡性结肠炎及氧化应激反应,与UC组相比,肠粘膜损伤降低,血浆总TNF-α、IL-6、IL-1、IL-10、MDA含量降低,SOD水平升高,同时Bcl-2蛋白表达水平显著升高,Bax和Caspase3蛋白表达水平明显降低(P<0.05),且其作用效果与SASP组没有显著性差异。结论青黛能减轻DSS诱导的小鼠溃疡性结肠炎的炎症反应、氧化应激和细胞凋亡。
Objective To investigate the protective effect and mechanism of indigo in mice ulcerative colitis induced by dextran sulfate. Methods 60 SPF grade male C57 BL/6 mice, with a body weight of 25-30 g, were randomly divided into control group(CON group), UC model group(UC group), salvia sulfonapyridine positive control group(SASP group), indigo low-dose group(LQD group), indigo medium-dose group(MQD group) and indigo high-dose group(HQD group), with 10 in each group. The UC model was established by DSS, and the effect of indigo on ulcerative colitis was evaluated by disease activity index score(DAI), HE staining, ELISA, immunohistochemistry and Western blot were used.Results The intestinal mucosa damage is serious, the total plasma values of TNF alpha, IL-6, IL-1, IL-10, MDA and SOD were decrease in UC group. The indigo naturalis inhibited the DSS of ulcerative colitis and oxidative stress reaction in mice,reduced intestinal mucosa damage and MDA, SOD levels, downregulated the total plasma values of TNF alpha, IL-6, IL-1,IL-10, upregulated Bcl-2 protein expression, decreased Bax and Caspase3 protein expression. Conclusion Indigo alleviated ulcerative colitis induced by DSS, which was related to the decreased inflammation, oxidative stress and apoptosis.
Objective To investigate the protective effect and mechanism of indigo in mice ulcerative colitis induced by dextran sulfate. Methods 60 SPF grade male C57 BL/6 mice, with a body weight of 25-30 g, were randomly divided into control group(CON group), UC model group(UC group), salvia sulfonapyridine positive control group(SASP group), indigo low-dose group(LQD group), indigo medium-dose group(MQD group) and indigo high-dose group(HQD group), with 10 in each group. The UC model was established by DSS, and the effect of indigo on ulcerative colitis was evaluated by disease activity index score(DAI), HE staining, ELISA, immunohistochemistry and Western blot were used.Results The intestinal mucosa damage is serious, the total plasma values of TNF alpha, IL-6, IL-1, IL-10, MDA and SOD were decrease in UC group. The indigo naturalis inhibited the DSS of ulcerative colitis and oxidative stress reaction in mice,reduced intestinal mucosa damage and MDA, SOD levels, downregulated the total plasma values of TNF alpha, IL-6, IL-1,IL-10, upregulated Bcl-2 protein expression, decreased Bax and Caspase3 protein expression. Conclusion Indigo alleviated ulcerative colitis induced by DSS, which was related to the decreased inflammation, oxidative stress and apoptosis.
引文
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[8]孟亚平.锡类散与美沙拉嗪肠溶片联用灌肠治疗直肠型溃疡性结肠炎患者的临床疗效评价[J].抗感染药学,2016,13(03):714-716.
[9]徐惠林,李昊,潘苏华,等.复方蛹虫草改善DSS联合高脂饮食诱导的溃疡性结肠炎的作用和机制[J].免疫学杂志,2017,33(05):422-426.
[10]Jiang F,Guo AP,Xu JC,et al.Discovery of a potent Grp94 selective inhibitor with anti-inflammatory efficacy in a mouse model of ulcerative colitis[J].J Med Chem,2018.doi:10.1021/acs.jmedchem.8b00800.
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[13]Barnes EL and Kappelman MD.Editorial:increasing incidence of pediatric inflammatory bowel disease in France:implications for etiology,diagnosis,prognosis,and treatment[J].Amer JGastroenterol,2018,113:273-275.
[14]闫曙光,惠毅,周永学.乌梅丸拆方对溃疡性结肠炎大鼠结肠TLR4/NF-κB信号通路的影响[J].时珍国医国药,2013,24(06):1386-1388.
[15]Levin L,Melignani E and Ramos AM.Effect of nitrogen sources and vitamins on ligninolytic enzyme production by some white-rot fungi.Dye decolorization by selected culture filtrates[J].Bioresource Technology,2010,101:4554-4563.
[16]Xiao HT,Peng J,Hu DD,et al.Qing-dai powder promotes recovery of colitis by inhibiting inflammatory responses of colonic macrophages in dextran sulfate sodium-treated mice[J].Chinese Med,2015,10:29.
[17]Wu C,Zhao J,Zhu G,et al.SiRNA directed against NFkappaBinhibits mononuclear macrophage cells releasing proinflammatory cytokines in vitro[J].Mol Med Reports,2017,16:9060-9066.
[18]Kawai S,Iijima H,Shinzaki S,et al.Indigo Naturalis ameliorates murine dextran sodium sulfate-induced colitis via aryl hydrocarbon receptor activation[J].J Gastroenterol,2017,52:904-919.
[19]Younus H.Therapeutic potentials of superoxide dismutase[J].Int JHealth Sci(Qassim),2018,2(3):88-93.
[2]Dubinsky MC.Reviewing treatments and outcomes in the evolving landscape of ulcerative colitis[J].Postgraduate Med,2017,129:538-553.
[3]柳越冬,陶弘武.加味通腑汤对溃疡性结肠炎大鼠超氧化物歧化酶和丙二醛影响的研究[J].中华中医药学刊,2017,35(4):775-778.
[4]Sparrow MP.Adalimumab in ulcerative colitis-efficacy,safety and optimization in the era of treat-to target[J].Expert Opinion on Biological Therapy,2017,17:613-621.
[5]Strik AS,Berends SE,Mathot RA,et al.Golimumab for moderate to severe ulcerative colitis[J].Expert Review of Gastroenterology&Hepatology,2017,11:401-406.
[6]Gao W,Zhang L,Wang X,et al.The combination of indirubin and isatin attenuates dextran sodium sulfate-induced ulcerative colitis in mice[J].Biochem Cell Biol,2018,96(5):636-645.
[7]Lai JL,Liu YH,Liu C,et al.Indirubin Inhibits LPS-Induced Inflammation via TLR4 Abrogation Mediated by the NF-kB and MAPK Signaling Pathways[J].Inflammation,2017,40:1-12.
[8]孟亚平.锡类散与美沙拉嗪肠溶片联用灌肠治疗直肠型溃疡性结肠炎患者的临床疗效评价[J].抗感染药学,2016,13(03):714-716.
[9]徐惠林,李昊,潘苏华,等.复方蛹虫草改善DSS联合高脂饮食诱导的溃疡性结肠炎的作用和机制[J].免疫学杂志,2017,33(05):422-426.
[10]Jiang F,Guo AP,Xu JC,et al.Discovery of a potent Grp94 selective inhibitor with anti-inflammatory efficacy in a mouse model of ulcerative colitis[J].J Med Chem,2018.doi:10.1021/acs.jmedchem.8b00800.
[11]Adams SM and Bornemann PH.Ulcerative colitis[J].Amer Family Physician,2013,87:699-705.
[12]Ng SC,Shi HY,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,2018,390:2769-2778.
[13]Barnes EL and Kappelman MD.Editorial:increasing incidence of pediatric inflammatory bowel disease in France:implications for etiology,diagnosis,prognosis,and treatment[J].Amer JGastroenterol,2018,113:273-275.
[14]闫曙光,惠毅,周永学.乌梅丸拆方对溃疡性结肠炎大鼠结肠TLR4/NF-κB信号通路的影响[J].时珍国医国药,2013,24(06):1386-1388.
[15]Levin L,Melignani E and Ramos AM.Effect of nitrogen sources and vitamins on ligninolytic enzyme production by some white-rot fungi.Dye decolorization by selected culture filtrates[J].Bioresource Technology,2010,101:4554-4563.
[16]Xiao HT,Peng J,Hu DD,et al.Qing-dai powder promotes recovery of colitis by inhibiting inflammatory responses of colonic macrophages in dextran sulfate sodium-treated mice[J].Chinese Med,2015,10:29.
[17]Wu C,Zhao J,Zhu G,et al.SiRNA directed against NFkappaBinhibits mononuclear macrophage cells releasing proinflammatory cytokines in vitro[J].Mol Med Reports,2017,16:9060-9066.
[18]Kawai S,Iijima H,Shinzaki S,et al.Indigo Naturalis ameliorates murine dextran sodium sulfate-induced colitis via aryl hydrocarbon receptor activation[J].J Gastroenterol,2017,52:904-919.
[19]Younus H.Therapeutic potentials of superoxide dismutase[J].Int JHealth Sci(Qassim),2018,2(3):88-93.