Experimental Medicine Research Center, Tehran University of Medical Sciences, 13145-784, Tehran, Iran.
Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
Dig Dis Sci. 2022 Aug;67(8):3672-3682. doi: 10.1007/s10620-021-07258-x. Epub 2021 Oct 21.
Recent investigations have proposed the potential role of gamma-aminobutyric acid (GABA) in regulating motility and immunity of the gastrointestinal system.
We aimed to investigate the anti-inflammatory effects of ivermectin (IVM) through GABA receptors following acetic acid-induced colitis in rats.
In a controlled experimental study, we enrolled 78 male Wistar rats (13 groups; 6 rats/group). After colitis induction using acetic acid (4%), IVM, baclofen (a standard GABA agonist) or the combination of both agents was delivered to rats orally (by gavage), with the same dosage continued for 5 days. The control group received the vehicle, and prednisolone (a standard anti-inflammatory agent) was administered in a separate group as the positive control. Colon samples were collected on the sixth day for histopathological evaluations and measurement of myeloperoxidase (MPO) activity, TNF-α levels, and p-NF-ĸB p65, COX-2 and iNOS expression levels.
The greatest recovery was found after administering IVM 0.5, baclofen 0.5, or IVM 0.2 + baclofen 0.2 mg/kg/day (ulcer index [UI] = 1.4 ± 0.4, 1.7 ± 0.6, and 1.4 ± 0.3, respectively; p < 0.001 vs. the control [UI = 6.5 ± 0.7]). Histopathological evaluations revealed a significant decrease in the inflammation severity in the three above-mentioned groups. P-NF-ĸB p65, COX-2, and iNOS expression, MPO activity, and TNF-α levels also decreased dramatically following treatment with IVM 0.5, baclofen 0.5, or the combination therapy (p < 0.001 vs. the control).
IVM exerted promising anti-inflammatory effects in treating acetic acid-induced colitis in rats. Its synergistic effect with baclofen also signified the possible involvement of GABA receptors in this process.
最近的研究提出了γ-氨基丁酸（GABA）在调节胃肠道运动和免疫方面的潜在作用。
我们旨在通过 GABA 受体研究伊维菌素（IVM）在乙酸诱导的大鼠结肠炎中的抗炎作用。
在一项对照实验研究中，我们纳入了 78 只雄性 Wistar 大鼠（分为 13 组；每组 6 只大鼠）。用乙酸（4%）诱导结肠炎后，大鼠经口（灌胃）给予 IVM、巴氯芬（一种标准的 GABA 激动剂）或两者联合用药，剂量相同，连续 5 天。对照组给予载体，另一组给予泼尼松龙（一种标准的抗炎药）作为阳性对照。第六天收集结肠样本进行组织病理学评估和髓过氧化物酶（MPO）活性、TNF-α 水平以及 p-NF-κB p65、COX-2 和 iNOS 表达水平的测定。
给予 IVM 0.5、巴氯芬 0.5 或 IVM 0.2+巴氯芬 0.2mg/kg/天时，恢复效果最佳（溃疡指数[UI]分别为 1.4±0.4、1.7±0.6 和 1.4±0.3；p<0.001 与对照组[UI=6.5±0.7]相比）。组织病理学评估显示，上述三组炎症严重程度均显著降低。MPO 活性、TNF-α 水平以及 p-NF-κB p65、COX-2 和 iNOS 表达也随着 IVM 0.5、巴氯芬 0.5 或联合治疗显著下降（p<0.001 与对照组相比）。
IVM 对乙酸诱导的大鼠结肠炎具有显著的抗炎作用。它与巴氯芬的协同作用表明 GABA 受体可能参与了这一过程。
