黄芪甲苷Ⅳ对溃疡性结肠炎大鼠的作用及其机制研究
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摘要
目的研究黄芪甲苷Ⅳ对溃疡性结肠炎(UC)大鼠的作用及其机制。方法用2,4,6-三硝基苯磺酸钠(TNBS)结肠灌注建立UC大鼠模型。按照体重将大鼠随机分为6组:正常组、模型组、对照组和低、中、高3个剂量实验组,每组10只。正常组与模型组给予0. 5%CMC-Na灌胃;对照组给予柳氮磺胺吡啶300 mg·kg~(-1)灌胃;低、中、高3个剂量实验组分别灌胃黄芪甲苷Ⅳ10,20,40mg·kg~(-1),1次/天,连续8 d。收集结肠并测定组织中髓过氧化物酶(MPO)活性;用酶联免疫吸附法检测结肠肿瘤坏死因子α(TNF-α)和白细胞介素1β(IL-1β)水平。结果正常组、模型组和低、中、高3个剂量实验组结肠组织MPO活性分别为(0. 11±0. 04),(4. 66±1. 22),(3. 63±0. 40),(3. 30±0. 68)和(2. 85±0. 57) U·mg~(-1);这5组结肠组织TNF-α含量分别为(176. 92±70. 27),(478. 96±91. 27),(357. 21±96. 22),(328. 37±99. 24)和(287. 09±87. 57) pg·mg~(-1);这5组结肠组织IL-1β水平分别为(402. 59±37. 58),(1045. 83±213. 59),(817. 93±104. 60),(772. 18±146. 94)和(717. 42±82. 44) pg·mg~(-1)。上述这3个指标:模型组与正常组比较,差异均有统计学意义(均P <0. 01); 3个剂量实验组与模型组比较,差异均有统计学意义(均P <0. 05)。结论黄芪甲苷Ⅳ可明显改善UC肠道病变,其作用与减轻炎症反应、提高黏膜屏障功能有关。
Objective To investigate the effect and underlying mechanism of astragaloside Ⅳ on ulcerative colitis( UC) in rats. Methods UC rat model was induced by 2,4,6-three sodium nitrobenzene sulfonate( TNBS) intra-colonic administration. The rats were randomly divided into 6 groups: normal group,model group,control group,as well as low,medium and high dose of experimental groups. Rats in normal group and model group were orally administered with 0. 5% CMC-Na,rats in control group were orally treated with salazosulfapyridine( 300 mg·kg~(-1)),while rats in experimental groups were orally administered with astragaloside Ⅳ at the dose of 10,20 and 40 mg. kg~(-1),respectively. All the drugs were administered for consecutive 8 days,1 times a day.Colon samples were collected for determining myeloperoxidase( MPO)activity. The level of tumor necrosis factor α( TNF-α) and interleukin-1β( IL-1β) in the colon were determined by enzyme linked immunosorbent assay. Results The MPO activity of colon tissue in normal group,model group,and the three dose of experimental groups were( 0. 11 ± 0. 04),( 4. 66 ± 1. 22),( 3. 63 ± 0. 40),( 3. 03 ± 0. 68),and( 2. 85 ± 0. 57) U · mg~(-1),respectively; the colonic TNF-α content in the 5 groups were( 176. 92 ± 70. 27),( 478. 96 ± 91. 27),( 357. 21 ± 96. 22),( 328. 37 ± 99. 24),and( 287. 09 ± 87. 57) pg·mg-1,respectively; the IL-1β content in the 5 groups were( 402. 59 ± 37. 58),( 1045. 83 ± 213. 59),( 817. 93 ± 104. 60),( 772. 18 ± 146. 94),and( 717. 42 ± 82. 44) pg·mg~(-1),respectively. Significant difference was found between normal group and model group( all P < 0. 01),and significant difference was also found between the three experimental groups and model group( all P < 0. 05). Conclusion Colonic damage in colitis rats was markedly improved by astragalosideⅣ treatment,this effect has close correlation with the decreased colonic inflammation and enhanced mucosa barrier function.
Objective To investigate the effect and underlying mechanism of astragaloside Ⅳ on ulcerative colitis( UC) in rats. Methods UC rat model was induced by 2,4,6-three sodium nitrobenzene sulfonate( TNBS) intra-colonic administration. The rats were randomly divided into 6 groups: normal group,model group,control group,as well as low,medium and high dose of experimental groups. Rats in normal group and model group were orally administered with 0. 5% CMC-Na,rats in control group were orally treated with salazosulfapyridine( 300 mg·kg~(-1)),while rats in experimental groups were orally administered with astragaloside Ⅳ at the dose of 10,20 and 40 mg. kg~(-1),respectively. All the drugs were administered for consecutive 8 days,1 times a day.Colon samples were collected for determining myeloperoxidase( MPO)activity. The level of tumor necrosis factor α( TNF-α) and interleukin-1β( IL-1β) in the colon were determined by enzyme linked immunosorbent assay. Results The MPO activity of colon tissue in normal group,model group,and the three dose of experimental groups were( 0. 11 ± 0. 04),( 4. 66 ± 1. 22),( 3. 63 ± 0. 40),( 3. 03 ± 0. 68),and( 2. 85 ± 0. 57) U · mg~(-1),respectively; the colonic TNF-α content in the 5 groups were( 176. 92 ± 70. 27),( 478. 96 ± 91. 27),( 357. 21 ± 96. 22),( 328. 37 ± 99. 24),and( 287. 09 ± 87. 57) pg·mg-1,respectively; the IL-1β content in the 5 groups were( 402. 59 ± 37. 58),( 1045. 83 ± 213. 59),( 817. 93 ± 104. 60),( 772. 18 ± 146. 94),and( 717. 42 ± 82. 44) pg·mg~(-1),respectively. Significant difference was found between normal group and model group( all P < 0. 01),and significant difference was also found between the three experimental groups and model group( all P < 0. 05). Conclusion Colonic damage in colitis rats was markedly improved by astragalosideⅣ treatment,this effect has close correlation with the decreased colonic inflammation and enhanced mucosa barrier function.
引文
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[2]KATSANOS K H,PAPADAKIS K A.Inflammatory bowel disease:updates on molecular targets for biologics[J].Gut liver,2017,11(4):455-463.
[3]曹玉冰.黄芪甲苷的药理作用及其机制的研究进展[J].现代药物与临床,2017,32(5):954-960.
[4]KARACA T,UZ Y H,DEMIRTAS S,et al.Protective effect of royal jelly in 2,4,6 trinitrobenzene sulfonic acid-induced colitis in rats[J]Iran J Basic Med Sci,2015,18(4):370-379.
[5]ASLANER A,CAKIR T,TEKELI S O,et al.Medical ozone treatment ameliorates the acute distal colitis in rat[J].Acta Cir Bras,2016,31(4):256-263.
[6]ZHAO L,WU H,ZHAO A,et al.The in vivo and in vitro study of polysaccharides from a two-herb formula on ulcerative colitis and potential mechanism of action[J].J Ethnopharmacol,2014,153(1):151-159.
[7]SHARMA D,MALIK A,GUY C S,et al.Pyrin inflammasome regulates tight junction integrity to restrict colitis and tumorigenesis[J].Gastroenterology,2018,154(4):948-964.
[8]LAUKOETTER M G,BRUEWER M,NUSRAT A.Regulation of the intestinal epithelial barrier by the apical junctional complex[J].Curr Opin Gastroenterol,2006,22(2):85-89.