Hua-Ying Fan, Wei-Wei Song, Ke Liu, Ming-Yan Yang, Xin Che, Hui Xu, School of Pharmacy, Yantai University, Yantai 264005, Shandong Province, China.
World J Gastroenterol. 2013 Dec 28;19(48):9318-27. doi: 10.3748/wjg.v19.i48.9318.
To evaluate the potential effectiveness of hydroxynaphthoquinone mixture (HM) in rats with 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis.
Colitis was induced by intracolonic administration of TNBS (80 mg/kg, dissolved in 50% ethanol). Rats were treated daily for 7 d with HM (2.5, 5, 10 mg/kg) and mesalazine 100 mg/kg 24 h after TNBS instillation. Disease progression was monitored daily by observation of clinical signs and body weight change. At the end of the experiment, macroscopic and histopathologic lesions of rats were scored, and myeloperoxidase (MPO) activity was determined. We also determined inflammatory cytokine tumor necrosis factor (TNF)-α level by ELISA, Western blotting and immunochemistry to explore the potential mechanisms of HM.
After intracolonic instillation of TNBS, animals developed colitis associated with soft stool, diarrhea and marked colonic destruction. Administration of HM significantly attenuated clinical and histopathologic severity of TNBS-induced colitis in a dose-dependent manner. It abrogated body weight loss, diarrhea and inflammation, decreased macroscopic damage score, and improved histological signs, with a significant reduction of inflammatory infiltration, ulcer size and the severity of goblet cell depletion (all P < 0.05 vs TNBS alone group). HM could reduce MPO activity. In addition, it also decreased serum TNF-α level and down-regulated TNF-α expression in colonic tissue. This reduction was statistically significant when the dose of HM was 10 mg/kg (P < 0.05 vs TNBS alone group), and the effect was comparable to that of mesalazine and showed no apparent adverse effect. The underlying mechanism may be associated with TNF-α inhibition.
These findings suggest that HM possesses favourable therapeutic action in TNBS-induced colitis, which provides direct pharmacological evidence for its clinical application.
评估羟基萘醌混合物（HM）在 2,4,6-三硝基苯磺酸（TNBS）诱导的结肠炎大鼠中的潜在疗效。
TNBS（80mg/kg，溶于 50%乙醇）经结肠内给药诱导结肠炎。在 TNBS 灌注后 24 小时，大鼠每日接受 HM（2.5、5、10mg/kg）和 100mg/kg 美沙拉嗪治疗 7 天。通过观察临床症状和体重变化，每天监测疾病进展。实验结束时，对大鼠的大体和组织病理学病变进行评分，并测定髓过氧化物酶（MPO）活性。我们还通过 ELISA、Western blot 和免疫组化测定炎症细胞因子肿瘤坏死因子（TNF）-α水平，以探讨 HM 的潜在机制。
TNBS 经结肠内灌注后，动物发生结肠炎，表现为软便、腹泻和明显的结肠破坏。HM 给药剂量依赖性地显著减轻 TNBS 诱导的结肠炎的临床和组织病理学严重程度。它阻止了体重减轻、腹泻和炎症，降低了大体损伤评分，并改善了组织学表现，减少了炎症浸润、溃疡大小和杯状细胞耗竭的严重程度（与 TNBS 单独组相比，均 P < 0.05）。HM 可以降低 MPO 活性。此外，它还降低了血清 TNF-α水平，并下调了结肠组织中的 TNF-α表达。当 HM 剂量为 10mg/kg 时，这种降低具有统计学意义（与 TNBS 单独组相比，P < 0.05），其效果与美沙拉嗪相当，且没有明显的不良反应。潜在的机制可能与 TNF-α抑制有关。
这些发现表明 HM 在 TNBS 诱导的结肠炎中具有良好的治疗作用，为其临床应用提供了直接的药理学证据。
