Department of Gastroenterology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China.
Institute of Digestive Diseases, China-Canada Center of Research for Digestive Diseases (ccCRDD), Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China.
World J Gastroenterol. 2017 Dec 21;23(47):8308-8320. doi: 10.3748/wjg.v23.i47.8308.
To investigate the effects of (PN) on microvascular injury in colitis, its mechanisms, initial administration time and dosage.
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.
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.
PN repairs vascular injury in experimental colitis attenuating inflammation and oxidative stress in the colonic mucosa. Efficacy is related to initial administration time and dose.
探讨（PN）对结肠炎微血管损伤的作用、机制、起始给药时间和剂量。
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，评价和研究 PN 乙醇提取物对微血管损伤及其相关机制的影响。模型建立后第 3 天和第 7 天开始给予 PN 治疗，剂量为 0.5、1.0 和 2.0 g/kg，连续 7 天。采用疾病活动指数（DAI）评估结肠炎的严重程度。显微镜下观察病理损伤。免疫组织化学法评估微血管密度（MVD）。采用 Evans 蓝法评估血管通透性。酶联免疫吸附试验检测血清细胞因子包括血管内皮生长因子（VEGF）A121、VEGFA165、白细胞介素（IL）-4、IL-6、IL-10 和肿瘤坏死因子（TNF）-α的浓度。测定髓过氧化物酶（MPO）和超氧化物歧化酶（SOD）评估氧化应激水平。Western blot 检测低氧诱导因子（HIF）-1α蛋白的表达。
DSS 和 IA 诱导的结肠炎大鼠结肠明显炎症和黏膜及微血管损伤。与正常对照组相比，结肠炎模型组 DAI 评分、血清 VEGFA121、VEGFA165、VEGFA165/VEGFA121、IL-6 和 TNF-α浓度以及结肠 MPO 和 HIF-1α浓度明显升高，而血清 IL-4 和 IL-10 浓度以及结肠 MVD 明显降低。PN 促进大鼠结肠炎结肠黏膜和微血管损伤修复，减轻炎症，降低 DAI 评分。PN 还降低了结肠炎大鼠血清 VEGFA121、VEGFA165、VEGFA165/VEGFA121、IL-6 和 TNF-α浓度以及结肠 MPO 和 HIF-1α浓度，增加了血清 IL-4 和 IL-10 浓度以及结肠 SOD 浓度。PN 的疗效与剂量有关。此外，PN 于第 3 天给药组的 DAI 评分明显低于第 7 天给药组。
PN 修复实验性结肠炎的血管损伤，减轻结肠黏膜的炎症和氧化应激。疗效与起始给药时间和剂量有关。
