板党多糖对溃疡性结肠炎大鼠的防治作用及其分子机制研究

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目的:观察板党多糖对2,4,6-三硝基苯磺酸(TNBS)诱导大鼠溃疡性结肠炎的防治作用并研究其机制。方法:SD大鼠60只,分为6组,每组10只,分别为正常组,模型组,板党多糖低、中、高(0.25,0.50,1.00 g·kg~(-1))剂量组,固肠止泻丸组(1.08 g·kg~(-1))。各组按各剂量ig给药5 d后,以TNBS 60 mg·kg~(-1)灌肠造模,再继续ig给药3周,每天1次。造模后第1,2,3及21天进行疾病活动指数(DAI)评价,末次给药30 min后乙醚麻醉,断头处死大鼠。取大鼠的结肠组织先进行黏膜损伤指数评价(CMDI),然后一半组织进行组织病理学检查及评分,另一半采用实时荧光定量-聚合酶链式反应(q PCR)检测Toll样受体4(TLR4),白细胞介素-6(IL-6),核因子-κB(NF-κB),肿瘤坏死因子-α(TNF-α)及白细胞介素-10(IL~(-1)0)的mRNA的表达。结果:与正常组比较,模型组大鼠结肠充血水肿,溃疡症状明显,组织病理学检查结果显示炎性细胞浸润较严重,CMDI评价及病理学组织评分明显升高,TLR4,IL-6,NF-κB,TNF-αmRNA表达明显升高,IL~(-1)0 mRNA表达明显降低(P<0.01);与模型组比较,板党多糖组大鼠结肠充血水肿,溃疡症状得到改善,组织病理学检查结果显示炎性细胞浸润情况明显改善,CMDI评价及病理学组织评分明显降低,对TLR4,IL-6,NF-κB,TNF-αmRNA表达具有下调作用,对IL~(-1)0 mRNA表达具有上调作用(P<0.05,P<0.01)。结论:板党多糖对TNBS诱导的大鼠溃疡性结肠炎呈现出良好的预防性治疗作用,其机制可能与调节TLR4,IL-6,NF-κB,TNF-α及IL~(-1)0水平有关。 OBJECTIVE: To observe the preventive and therapeutic effects of Radix Bupleuri on polysaccharides from 2,4,6-trinitrobenzene sulfonic acid (TNBS) -induced ulcerative colitis in rats and its mechanism. Methods: Sixty Sprague-Dawley rats were randomly divided into six groups (n = 10, n = 10). The normotensive groups were normal, model group, low, medium and high doses of Radix Codonopsis (0.25,0.50,1.00 g · kg -1) Group and Guchang Zhixie Pill group (1.08 g · kg -1). The rats in each group were dosed with ig for 5 days at each dose, then were given enema of TNBS at a dose of 60 mg · kg -1 for 3 weeks and once a day. The disease activity index (DAI) was evaluated on the 1st, 2nd, 21st and 21st days after modeling. The rats were anesthetized by ether 30min after the last administration, and the rats were sacrificed. Colon mucosal injury index (CMDI) was taken from the rats’ colon tissues, then half of them were histopathologically examined and scored. The other half was examined by real-time qPCR (q PCR) for Toll-like receptor 4 TLR4, IL-6, NF-κB, TNF-α and IL-10 mRNA expression. Results: Compared with the normal group, the rats in the model group had congestion and edema in the colon and obvious ulcer symptoms. The results of histopathological examination showed that the infiltration of inflammatory cells was more serious, the CMDI score and histopathological score were significantly higher, and TLR4, IL-6 and NF (P <0.01). Compared with the model group, the symptoms of colonic congestion and edema and ulcer were improved in the group of Codonopsis pilosula polysaccharides, and the expression of TNF-αmRNA, Nephrology results showed that infiltration of inflammatory cells was significantly improved, CMDI score and pathological tissue score were significantly decreased, and down-regulated the expression of TLR4, IL-6, NF-κB and TNF-αmRNA, The expression was up-regulated (P <0.05, P <0.01). CONCLUSION: PAN has a good preventive effect on TNBS-induced ulcerative colitis in rats. The mechanism may be related to the regulation of TLR4, IL-6, NF-κB, TNF-α and IL-1 Horizontal related.
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