Effects of initiating time and dosage of Panax notoginseng on mucosal microvascular injury in experimental colitis.
Effects of initiating time and dosage of Panax notoginseng on mucosal microvascular injury in experimental colitis.
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三七起始时间和剂量对实验性结肠炎黏膜微血管损伤的影响
DOI：
10.3748/wjg.v23.i47.8308
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发表时间：
2017-12-21
影响因子：
4.3
通讯作者：
Lin J
中科院分区：
文献类型：
--
作者：
Wang SY;Tao P;Hu HY;Yuan JY;Zhao L;Sun BY;Zhang WJ;Lin J
目的探讨三七(PN)对结肠炎微血管损伤的影响及其作用机制、初始给药时间和剂量。方法采用葡聚糖硫酸钠(DSS)或碘乙酰胺(IA)诱导的大鼠结肠炎模型，观察PN乙醇提取物对大鼠结肠炎微血管损伤的影响及其机制。分别于造模后3d、7d开始给药，剂量分别为0.5、1.0、2.0g/kg，连续7d，用疾病活动性指数(DAI)评价结肠炎的严重程度。显微镜下观察病理组织学改变。免疫组织化学方法检测微血管密度(MVD)。伊文思蓝法测定血管通透性。用双抗体夹心酶联免疫吸附试验检测血清中血管内皮生长因子A121、血管内皮细胞生长因子165、白介素4、白介素6、白介素10和肿瘤坏死因子α的浓度。测定髓过氧化物酶(MPO)和超氧化物歧化酶(SOD)以评估氧化应激水平。免疫印迹法检测缺氧诱导因子-1α蛋白的表达。结果DSS和IA诱导的大鼠结肠炎模型均有明显的结肠炎症反应，黏膜和微血管损伤明显。结肠炎模型组DAI评分、血清VEGFA121、VEGFA165、VEGFA165/VEGFA121、IL-6、肿瘤坏死因子-α水平及结肠组织MPO、HIF-1α水平显著高于正常对照组，而血清IL-4、IL-10水平及结肠微血管密度显著低于正常对照组。PN可促进结肠炎大鼠结肠黏膜和微血管损伤的修复，减轻炎症反应，降低DAI评分。PN还能降低血清中VEGFA121、VEGFA165、VEGFA165/VEGFA121、IL-6和肿瘤坏死因子-α的浓度及结肠组织中髓过氧化物酶和缺氧诱导因子-1α的浓度，升高血清中IL-4和IL-10的浓度以及结肠组织中超氧化物歧化酶的浓度。胃肠外营养的疗效呈剂量依赖性。此外，第3天PN组DAI评分明显低于第7天PN组。结论PN通过减轻结肠黏膜炎症和氧化应激来修复实验性结肠炎的血管损伤。疗效与首次给药时间和剂量有关。
AIM To investigate the effects of Panax notoginseng (PN) on microvascular injury in colitis, its mechanisms, initial administration time and dosage. METHODS Dextran sodium sulfate (DSS)- or iodoacetamide (IA)-induced rat colitis models were used to evaluate and investigate the effects of ethanol extract of PN on microvascular injuries and their related mechanisms. PN administration was initiated at 3 and 7 d after the model was established at doses of 0.5, 1.0 and 2.0 g/kg for 7 d. The severity of colitis was evaluated by disease activity index (DAI). The pathological lesions were observed under a microscope. Microvessel density (MVD) was evaluated by immunohistochemistry. Vascular permeability was evaluated using the Evans blue method. The serum concentrations of cytokines, including vascular endothelial growth factor (VEGF)A121, VEGFA165, interleukin (IL)-4, IL-6, IL-10 and tumor necrosis factor (TNF)-α, were detected by enzyme-linked immunosorbent assay. Myeloperoxidase (MPO) and superoxide dismutase (SOD) were measured to evaluate the level of oxidative stress. Expression of hypoxia-inducible factor (HIF)-1α protein was detected by western blotting. RESULTS Obvious colonic inflammation and injuries of mucosa and microvessels were observed in DSS- and IA-induced colitis groups. DAI scores, serum concentrations of VEGFA121, VEGFA165, VEGFA165/VEGFA121, IL-6 and TNF-α, and concentrations of MPO and HIF-1α in the colon were significantly higher while serum concentrations of IL-4 and IL-10 and MVD in colon were significantly lower in the colitis model groups than in the normal control group. PN promoted repair of injuries of colonic mucosa and microvessels, attenuated inflammation, and decreased DAI scores in rats with colitis. PN also decreased the serum concentrations of VEGFA121, VEGFA165, VEGFA165/VEGFA121, IL-6 and TNF-α, and concentrations of MPO and HIF-1α in the colon, and increased the serum concentrations of IL-4 and IL-10 as well as the concentration of SOD in the colon. The efficacy of PN was dosage dependent. In addition, DAI scores in the group administered PN on day 3 were significantly lower than in the group administered PN on day 7. CONCLUSION PN repairs vascular injury in experimental colitis via attenuating inflammation and oxidative stress in the colonic mucosa. Efficacy is related to initial administration time and dose.
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