铁皮石斛提取物对DSS诱导的溃疡性结肠炎小鼠的抗氧化及抗炎作用
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摘要
目的:观察铁皮石斛提取物对葡聚糖硫酸钠(DSS)诱导的溃疡性结肠炎小鼠抗氧化、抗炎能力的影响。初步探讨铁皮石斛提取物治疗溃疡性结肠炎的作用机制。方法:将小鼠随机分为正常对照组、DSS模型组、5-氨基水杨酸(5-ASA)阳性药物对照组、铁皮石斛提取物低、中、高(200,400,800 mg·kg-1)剂量组,除正常对照组外,其余各组采用4%的DSS自由饮用建立小鼠溃疡性结肠炎模型。5-ASA阳性药物对照组和铁皮石斛提取物治疗组在造模d 1开始灌胃(ig)给药,连续给药10 d后处死各组小鼠,留取结肠组织,对各组小鼠结肠组织进行大体与组织病理学损伤评分。运用蛋白免疫印迹技术(Western Blot)检测小鼠结肠组织中c-Jun,c-Fos的表达,酶联免疫法(ELISA)检测结肠组织中丙二醛(MDA)、诱导型一氧化氮合酶(i NOS)、NO、谷胱甘肽过氧化物酶(GSH-Px)、谷胱甘肽(GSH)、超氧化物歧化酶(SOD)、总的一氧化氮合酶(TNOS)的含量。同时,眼眶取血,收集血清,ELISA检测血清中干扰素IFN-γ,TNF-α的含量。结果:与正常对照组比较,DSS模型组小鼠结肠大体评分与组织病理学损伤评分显著增加(P <0. 01)。与模型组比较,铁皮石斛提取物不同剂量组小鼠结肠组织大体评分和组织病理学损伤评分降低(P <0. 05或P <0. 01);血清中干扰素(IFN-γ,TNF-α)的含量明显降低(P <0. 05);结肠组织中c-Jun,c-Fos蛋白表达显著降低(P <0. 05);结肠组织中MDA,i NOS,NO,TNOS含量显著降低(P <0. 01或P <0. 05);而结肠组织中GSH-Px,GSH,SOD含量明显升高(P <0. 01)。结论:研究表明铁皮石斛提取物具有治疗DSS诱导的小鼠溃疡性结肠炎的作用,其作用机制之一是通过清除自由基、修复氧化损伤和提高细胞抗氧化能力,重新建立氧化还原平衡,同时,抑制炎症因子IFN-γ,TNF-α的释放和c-Jun,c-Fos的高表达,进而抑制结肠炎症。
Objective: To observe the anti-oxidation and anti-inflammatory effects of Dendrobium officinale extract on dextran sodium sulfate( DSS)-induced ulcerative colitis in mice,and preliminarily disccuss the therapeutie mechanism of Dendrobium officinale extract on ulcerative colitis. Methods: Mice were randomly divided into normal control group,DSS model group,5-ASA treatment group,Dendrobium officinale extract low-,middle-,and high-dose( 200,400,800 mg·kg-1) treatment group. Except the normal control group,all the other groups were treated with 4% DSS to induce the ulcerative colitis model. From the first day of modeling,5-ASA and different concentrations of Dendrobium officinale were given by gavage for 10 days continuously. The mice were killed after drug treatment for 10 days,and the colon was taken. The colonic injury and inflammation were assessed by macroscopicand microscopic damage scores. The expression levels of c-Jun and c-Fos in colon were measured by Western blot,while the levels of MDA,i NOS,NO,GSH-Px,GSH,SOD and TNOS were measured by ELISA. Meanwile,the serum was collected to detect the levels of IFN-γ and TNF-α by ELISA. Results: As compared with the normal control group,the colonic injuryand pathological scores in the model group were significantly higher( P < 0. 01).In comparison with the model group,Dendrobium officinale extract of different concentrations reduced the colonic injury and pathological scores( P < 0. 05 or P < 0. 01). At the same time,the concentrations of IFN-γ and TNF-αin serum were decreased( P < 0. 05); c-Jun and c-Fos protein expressions in the colon tissue were also reduced significantly( P < 0. 05); the concentrations of MDA,i NOS,NO,TNOS in the colon tissue were decreased significantly( P < 0. 01 or P < 0. 05); while the concentrations of GSH-Px,GSH,and SOD were increased obviously( P < 0. 01). Conclusion: Dendrobium officinale extract has a curative effect on UC mice induced by DSS. The mechanism is to scavenge free radicals and increase the anti-oxidative capacity of cells in a degree,and re-establish the redox balance. In addition,Dendrobium officinale extract also reduces the release of IFN-γ and TNF-α. It inhibits the high expressions of c-Jun,c-Fos and eventually inhibits ulcerative colitis.
Objective: To observe the anti-oxidation and anti-inflammatory effects of Dendrobium officinale extract on dextran sodium sulfate( DSS)-induced ulcerative colitis in mice,and preliminarily disccuss the therapeutie mechanism of Dendrobium officinale extract on ulcerative colitis. Methods: Mice were randomly divided into normal control group,DSS model group,5-ASA treatment group,Dendrobium officinale extract low-,middle-,and high-dose( 200,400,800 mg·kg-1) treatment group. Except the normal control group,all the other groups were treated with 4% DSS to induce the ulcerative colitis model. From the first day of modeling,5-ASA and different concentrations of Dendrobium officinale were given by gavage for 10 days continuously. The mice were killed after drug treatment for 10 days,and the colon was taken. The colonic injury and inflammation were assessed by macroscopicand microscopic damage scores. The expression levels of c-Jun and c-Fos in colon were measured by Western blot,while the levels of MDA,i NOS,NO,GSH-Px,GSH,SOD and TNOS were measured by ELISA. Meanwile,the serum was collected to detect the levels of IFN-γ and TNF-α by ELISA. Results: As compared with the normal control group,the colonic injuryand pathological scores in the model group were significantly higher( P < 0. 01).In comparison with the model group,Dendrobium officinale extract of different concentrations reduced the colonic injury and pathological scores( P < 0. 05 or P < 0. 01). At the same time,the concentrations of IFN-γ and TNF-αin serum were decreased( P < 0. 05); c-Jun and c-Fos protein expressions in the colon tissue were also reduced significantly( P < 0. 05); the concentrations of MDA,i NOS,NO,TNOS in the colon tissue were decreased significantly( P < 0. 01 or P < 0. 05); while the concentrations of GSH-Px,GSH,and SOD were increased obviously( P < 0. 01). Conclusion: Dendrobium officinale extract has a curative effect on UC mice induced by DSS. The mechanism is to scavenge free radicals and increase the anti-oxidative capacity of cells in a degree,and re-establish the redox balance. In addition,Dendrobium officinale extract also reduces the release of IFN-γ and TNF-α. It inhibits the high expressions of c-Jun,c-Fos and eventually inhibits ulcerative colitis.
引文
[1] DEROCHE TC,XIAO SY,LIU X. Histological evaluation in ulcerative colitis[J]. Gastroenterol Rep,2014,2(3):178-192.
[2]王玉芳,欧阳钦,胡仁伟,等.炎症性肠病流行病学研究进展[J].胃肠病学,2013,18(1):48-51.
[3] KRISHNAREDDY S,SWAMINATH A. When combination therapy isn’t working:emerging therapies for the management of inflammatory bowel disease[J]. World J Gastroenterol,2014,20(5):1139-1146.
[4]孙恒,胡强,金航,等.铁皮石斛化学成分及药理活性研究进展[J].中国实验方剂学杂志,2017,23(11):225-234.
[5] LI GJ,SUN P,WANG Q,et al. Dendrobium candidum Wall. ex Lindl. attenuates CCl4-induced hepatic damage in imprinting control region mice[J]. Exp Ther Med,2014,8(3):1015-1021.
[6] WANG Q,SUN P,LI G,et al. Inhibitory effects of Dendrobium candidum Wall ex Lindl. on azoxymethane and dextran sulfate sodiuminduced colon carcinogenesis in C57BL/6 mice[J]. Oncol Lett,2014,7(2):493-498.
[7]罗爽,罗霞,刘琦,等.大黄酸对DSS诱导溃疡性结肠炎小鼠的治疗作用及机制探讨[J].中国实验方剂学杂志,2017,23(11):109-113.
[8] GALVEZ J,COELHO G,CRESPO ME. Intestinal anti-in-flammatory activity of morin on chronic experimen-tal colitis in the rat[J]. Aliment Pharmacol Ther,2001,15(12):2027-2039.
[9]王艳红,丁义兰,杨孝来,等.葡萄籽原花青素对复发性结肠炎大鼠结肠组织中c-Jun、c-Fos表达的影响[J].中国临床药理学与治疗学,2011,16(9):992-997.
[10] REN Y,GENG Y,DU Y,et al. Polysaccharide of Hericium erinaceus attenuates colitis in C57BL/6 mice via regulation of oxidative stress,inflammation-related signaling pathways and modulating the composition of the gut microbiota[J]. J Nutr Biochem,2018,7(57):67-76.
[11]孙阿宁,任改艳,邓超,等.牡荆素减轻小鼠溃疡性结肠炎的药效作用及机制研究[J].中国药理学通报,2014,30(12):1677-1680.
[12]周毅骏,钦丹萍,杨强,等.雷公藤多苷对TNBS/乙醇溃疡性结肠炎大鼠脂质过氧化损伤的保护作用[J].中药药理与临床,2017,33(5):77-81.
[13]周燕红,何小飞,白育庭,等.银杏叶提取物对大鼠实验性结肠炎肿瘤坏死因子-α表达的影响[J].中国药理学通报,2007,23(12):1605-1609.
[14] CANBAKAN B,KOROGLU E,ATAY K,et al. Assessment of oxidative stress parameters for the disease activity evaluation in patients with ulcerative colitis[J]. J Crohns Colitis,2016,10:173.
[15] PETRONILHO F,MICHELS M,DANIELSKI LG,et al. Diphenyl diselenide attenuates oxidative stress and inflammatory parameters in ulcerative colitis:a comparison with ebselen[J]. Pathol Res Pract,2016,212(9):755-760.
[16] BANK S,ANDERSEN PS,BURISCH J,et al. Associations between functional polymorphisms in the NF-κB signaling pathway and response to anti-TNF treatment in Danish patients with inflammatory bowel disease[J]. Pharmacogenomics J,2014,14(6):526-534.
[17]穆敬平,刘莉,方伟,等.实验性结肠炎大鼠结肠c-fos原癌基因表达的变化[J].胃肠病学和肝病学杂志,2010,11(11):988-990.
[18] INDARAM AV,VISVALINGAM V,LOCKE M,et al. Mucosal cytokine pro-duction in radiation-induced proctosigmoiditis compared with inflam-matory bowel disease[J]. Am J Gastroenterol,2000,95(3):1221-1225.
[2]王玉芳,欧阳钦,胡仁伟,等.炎症性肠病流行病学研究进展[J].胃肠病学,2013,18(1):48-51.
[3] KRISHNAREDDY S,SWAMINATH A. When combination therapy isn’t working:emerging therapies for the management of inflammatory bowel disease[J]. World J Gastroenterol,2014,20(5):1139-1146.
[4]孙恒,胡强,金航,等.铁皮石斛化学成分及药理活性研究进展[J].中国实验方剂学杂志,2017,23(11):225-234.
[5] LI GJ,SUN P,WANG Q,et al. Dendrobium candidum Wall. ex Lindl. attenuates CCl4-induced hepatic damage in imprinting control region mice[J]. Exp Ther Med,2014,8(3):1015-1021.
[6] WANG Q,SUN P,LI G,et al. Inhibitory effects of Dendrobium candidum Wall ex Lindl. on azoxymethane and dextran sulfate sodiuminduced colon carcinogenesis in C57BL/6 mice[J]. Oncol Lett,2014,7(2):493-498.
[7]罗爽,罗霞,刘琦,等.大黄酸对DSS诱导溃疡性结肠炎小鼠的治疗作用及机制探讨[J].中国实验方剂学杂志,2017,23(11):109-113.
[8] GALVEZ J,COELHO G,CRESPO ME. Intestinal anti-in-flammatory activity of morin on chronic experimen-tal colitis in the rat[J]. Aliment Pharmacol Ther,2001,15(12):2027-2039.
[9]王艳红,丁义兰,杨孝来,等.葡萄籽原花青素对复发性结肠炎大鼠结肠组织中c-Jun、c-Fos表达的影响[J].中国临床药理学与治疗学,2011,16(9):992-997.
[10] REN Y,GENG Y,DU Y,et al. Polysaccharide of Hericium erinaceus attenuates colitis in C57BL/6 mice via regulation of oxidative stress,inflammation-related signaling pathways and modulating the composition of the gut microbiota[J]. J Nutr Biochem,2018,7(57):67-76.
[11]孙阿宁,任改艳,邓超,等.牡荆素减轻小鼠溃疡性结肠炎的药效作用及机制研究[J].中国药理学通报,2014,30(12):1677-1680.
[12]周毅骏,钦丹萍,杨强,等.雷公藤多苷对TNBS/乙醇溃疡性结肠炎大鼠脂质过氧化损伤的保护作用[J].中药药理与临床,2017,33(5):77-81.
[13]周燕红,何小飞,白育庭,等.银杏叶提取物对大鼠实验性结肠炎肿瘤坏死因子-α表达的影响[J].中国药理学通报,2007,23(12):1605-1609.
[14] CANBAKAN B,KOROGLU E,ATAY K,et al. Assessment of oxidative stress parameters for the disease activity evaluation in patients with ulcerative colitis[J]. J Crohns Colitis,2016,10:173.
[15] PETRONILHO F,MICHELS M,DANIELSKI LG,et al. Diphenyl diselenide attenuates oxidative stress and inflammatory parameters in ulcerative colitis:a comparison with ebselen[J]. Pathol Res Pract,2016,212(9):755-760.
[16] BANK S,ANDERSEN PS,BURISCH J,et al. Associations between functional polymorphisms in the NF-κB signaling pathway and response to anti-TNF treatment in Danish patients with inflammatory bowel disease[J]. Pharmacogenomics J,2014,14(6):526-534.
[17]穆敬平,刘莉,方伟,等.实验性结肠炎大鼠结肠c-fos原癌基因表达的变化[J].胃肠病学和肝病学杂志,2010,11(11):988-990.
[18] INDARAM AV,VISVALINGAM V,LOCKE M,et al. Mucosal cytokine pro-duction in radiation-induced proctosigmoiditis compared with inflam-matory bowel disease[J]. Am J Gastroenterol,2000,95(3):1221-1225.
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