Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran; Department of Pharmacology, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
Physiology and Pharmacology Research Center, Rafsanjan University of Medical Sciences, Rafsanjan, Iran; Department of Physiology and Pharmacology, Faculty of Medicine, Rafsanjan, University of Medical Sciences, Rafsanjan, Iran.
Pharmacol Rep. 2018 Jun;70(3):426-433. doi: 10.1016/j.pharep.2017.11.010. Epub 2017 Nov 22.
Colitis, a colonic inflammatory condition, showed a linkage with hepatobiliary disorders such as cirrhosis. It has been reported that both endogenous opioids and nitric oxide (NO) play critical roles in colitis pathogenesis. Moreover, opioid and NO levels showed elevation in patients with cirrhosis. The aim of this study was to evaluate the effect of cirrhosis on the experimental model of colitis and the possible involvement of opioidergic/nitrergic systems in rats.
Colitis was induced by acetic acid 28days after bile duct ligation (BDL). L-NAME, as an inhibitor of NO synthase and naltrexone, as an antagonist of opioid receptors were administered intraperitoneally to animals during 3days after induction of colitis. Macroscopic colitis lesion area, inflammatory mediators change, NO metabolite levels, and colon microscopic injuries were assessed 3days after induction.
Cirrhosis significantly reduced the severity of damages to the colon. Administration of L-NAME (10mg/kg), naltrexone (10mg/kg) and co-administration of L-NAME (1mg/kg) and naltrexone (5mg/kg) significantly decreased the protective effect of BDL on colitis. Nitrite elevated levels in BDL rats were significantly diminished in L-NAME- and naltrexone-treated animals. Histopathology parameters and cytokines level alterations in the colon of acetic acid-treated animals after BDL was reversed after injection of L-NAME, naltrexone, and co-administration of L-NAME (1mg/kg) + naltrexone (5mg/kg).
Cirrhosis improved the intestinal damages induced by acetic acid in rats which may be mediated through interaction of nitrergic and opioidergic systems.
结肠炎是一种结肠炎症性疾病，与肝硬化等肝胆疾病有关。据报道，内源性阿片肽和一氧化氮（NO）在结肠炎发病机制中起关键作用。此外，肝硬化患者的阿片肽和 NO 水平升高。本研究旨在评估肝硬化对结肠炎实验模型的影响，以及阿片肽/NO 系统在大鼠中的可能参与。
在胆管结扎（BDL）后 28 天用乙酸诱导结肠炎。在诱导结肠炎后 3 天内，通过腹膜内给予 L-NAME（NO 合酶抑制剂）和纳曲酮（阿片受体拮抗剂）来评估动物的大体结肠炎病变面积、炎症介质变化、NO 代谢物水平和结肠微观损伤。
肝硬化显著减轻了结肠损伤的严重程度。给予 L-NAME（10mg/kg）、纳曲酮（10mg/kg）和 L-NAME（1mg/kg）和纳曲酮（5mg/kg）联合给药显著降低了 BDL 对结肠炎的保护作用。BDL 大鼠的硝酸盐水平升高，在给予 L-NAME 和纳曲酮的动物中明显降低。在 BDL 后用乙酸处理的动物的结肠组织病理学参数和细胞因子水平的改变在给予 L-NAME、纳曲酮和 L-NAME（1mg/kg）+纳曲酮（5mg/kg）联合给药后被逆转。
肝硬化改善了大鼠乙酸诱导的肠道损伤，这可能是通过氮能和阿片能系统的相互作用介导的。
