Department of Physiology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
World J Gastroenterol. 2012 Apr 7;18(13):1479-84. doi: 10.3748/wjg.v18.i13.1479.
To investigate the effects of curcumin on gastric microcirculation and inflammation in rats with indomethacin-induced gastric damage.
Male Sprague-Dawley rats were randomly divided into three groups. Group 1 (control group, n = 5) was fed with olive oil and 5% NaHCO(3) (-) (vehicle). Group 2 [indomethacin (IMN) group, n = 5] was fed with olive oil 30 min prior to indomethacin 150 mg/kg body weight (BW) dissolved in 5% NaHCO(3) (-) at time 0th and 4th h. Group 3 (IMN + Cur group, n = 4) was fed with curcumin 200 mg/kg BW dissolved in olive oil 0.5 mL, 30 min prior to indomethacin at 0th and 4th h. Leukocyte-endothelium interactions at postcapillary venules were recorded after acridine orange injection. Blood samples were determined for intercellular adhesion molecule (ICAM)-1 and tumor necrosis factor (TNF)-α levels using enzyme linked immunosorbent assay method. Finally, the stomach was removed for histopathological examination for gastric lesions and grading for neutrophil infiltration.
In group 2, the leukocyte adherence in postcapillary venules was significantly increased compared to the control group (6.40 ± 2.30 cells/frame vs 1.20 ± 0.83 cells/frame, P = 0.001). Pretreatment with curcumin caused leukocyte adherence to postcapillary venule to decline (3.00 ± 0.81 cells/frame vs 6.40 ± 2.30 cells/frame, P = 0.027). The levels of ICAM-1 and TNF-α increased significantly in the indomethacin-treated group compared with the control group (1106.50 ± 504.22 pg/mL vs 336.93 ± 224.82 pg/mL, P = 0.011 and 230.92 ± 114.47 pg/mL vs 47.13 ± 65.59 pg/mL, P = 0.009 respectively). Pretreatment with curcumin significantly decreased the elevation of ICAM-1 and TNF-α levels compared to treatment with indomethacin alone (413.66 ± 147.74 pg/mL vs 1106.50 ± 504.22 pg/mL, P = 0.019 and 58.27 ± 67.74 pg/mL vs 230.92 ± 114.47 pg/mL, P = 0.013 respectively). The histological appearance of the stomach in the control group was normal. In the indomethacin-treated group, the stomachs showed a mild to moderate neutrophil infiltration score. Gastric lesions were erosive and ulcerative. In rats treated with indomethacin and curcumin, stomach histopathology improved and showed only a mild neutrophil infiltration score and fewer erosive lesions in the gastric mucosa.
The results indicate that curcumin prevents indomethacin-induced gastropathy through the improvement of gastric microcirculation by attenuating the level of ICAM-1 and TNF-α.
研究姜黄素对吲哚美辛诱导的大鼠胃损伤胃微循环和炎症的影响。
雄性 Sprague-Dawley 大鼠随机分为 3 组。第 1 组(对照组,n = 5)给予橄榄油和 5%碳酸氢钠(-)(载体)。第 2 组[吲哚美辛(IMN)组,n = 5]在第 0 小时和第 4 小时给予溶于 5%碳酸氢钠(-)的 150mg/kg 体重的吲哚美辛,同时给予橄榄油。第 3 组(IMN+Cur 组,n = 4)在第 0 小时和第 4 小时给予溶于橄榄油的 200mg/kg 体重的姜黄素,同时给予橄榄油 30 分钟。在阿霉素注射后记录后微静脉白细胞-内皮细胞相互作用。采用酶联免疫吸附试验法测定细胞间黏附分子(ICAM)-1 和肿瘤坏死因子(TNF)-α水平。最后,切除胃进行胃损伤和中性粒细胞浸润分级的组织病理学检查。
与对照组相比,第 2 组的后微静脉白细胞黏附明显增加(6.40 ± 2.30 个/框 vs 1.20 ± 0.83 个/框,P = 0.001)。用姜黄素预处理后,后微静脉白细胞黏附下降(3.00 ± 0.81 个/框 vs 6.40 ± 2.30 个/框,P = 0.027)。与对照组相比,吲哚美辛治疗组的 ICAM-1 和 TNF-α水平明显升高(1106.50 ± 504.22 pg/ml vs 336.93 ± 224.82 pg/ml,P = 0.011 和 230.92 ± 114.47 pg/ml vs 47.13 ± 65.59 pg/ml,P = 0.009)。与单独使用吲哚美辛相比,用姜黄素预处理显著降低了 ICAM-1 和 TNF-α水平的升高(413.66 ± 147.74 pg/ml vs 1106.50 ± 504.22 pg/ml,P = 0.019 和 58.27 ± 67.74 pg/ml vs 230.92 ± 114.47 pg/ml,P = 0.013)。对照组胃的组织学表现正常。在吲哚美辛治疗组,胃出现轻度至中度中性粒细胞浸润评分。胃损伤呈糜烂和溃疡。在用吲哚美辛和姜黄素治疗的大鼠中,胃组织病理学改善,仅表现出轻度中性粒细胞浸润评分和胃黏膜糜烂性病变减少。
结果表明,姜黄素通过降低 ICAM-1 和 TNF-α水平改善胃微循环,从而预防吲哚美辛诱导的胃病。