Zandeh-Rahimi Yaser, Panahi Negar, Hesaraki Saeed, Shirazi-Beheshtiha Seyed Hamed
Department of Veterinary Basic Sciences, Science and Research Branch, Islamic Azad University, Tehran, Iran.
Department of Veterinary Pathobiology, Science and Research Branch, Islamic Azad University, Tehran, Iran.
Int J Pept Res Ther. 2022;28(1):43. doi: 10.1007/s10989-021-10314-9. Epub 2022 Jan 3.
Phoenixin-14 (PNX-14) is a newly identified neuropeptide with potential anti-inflammatory effects in the gastrointestinal tract. In this study, we evaluated the protective effect of PNX-14 against the formation of experimental indomethacin (IND)-induced duodenal ulcer. Thirty-two male Sprague-Dawley rats were randomly assigned to the four following study groups: (1) negative control (2) IND (7.5 mg/kg subcutaneous IND), (3) famotidine (FA) (7.5 mg/kg subcutaneous IND followed by 40 mg/kg intraperitoneal FA), and (4) PNX-14 (7.5 mg/kg subcutaneous IND followed by 50 µ/kg intraperitoneal PNX-14). Outcome measures included macroscopic evaluation of duodenal lesion, serum levels of IL-1ß, TNF-α, IL-6, and IL-12, and tissue biochemical parameters of oxidative stress, including malondialdehyde (MDA), myeloperoxidase (MPO) activity, superoxide dismutase (SOD) activity, and catalase activity. Results The macroscopic grade of duodenal lesions were significantly smaller in the PNX-14 group than in the IND group (p < 0.001). Serum inflammatory cytokines were significantly increased in the IND group. PNX-14 treatment significantly decreased the serum levels of inflammatory cytokines (p < 0.0001). Oxidative contents (MDA and MPO activity) were significantly smaller in the PNX-14 group compared with the IND group (p < 0.0001), while anti-oxidative contents (SOD and catalase activity) were significantly more (p < 0.0001). PNX-14 was superior to FA in several anti-inflammatory properties, such as inhibiting the release of inflammatory cytokines and increasing the catalase activity. PNX-14 showed significant protective effects against the formation of IND-induced duodenal ulcers. These results suggest a promising therapeutic implication for PNX-14 in the treatment of gastrointestinal inflammatory disorders.
凤凰肽-14(PNX-14)是一种新发现的神经肽,在胃肠道中具有潜在的抗炎作用。在本研究中,我们评估了PNX-14对实验性吲哚美辛(IND)诱导的十二指肠溃疡形成的保护作用。32只雄性Sprague-Dawley大鼠被随机分为以下四个研究组:(1)阴性对照组;(2)IND组(皮下注射7.5mg/kg IND);(3)法莫替丁(FA)组(皮下注射7.5mg/kg IND,随后腹腔注射40mg/kg FA);(4)PNX-14组(皮下注射7.5mg/kg IND,随后腹腔注射50µ/kg PNX-14)。观察指标包括十二指肠病变的宏观评估、血清白细胞介素-1β(IL-1β)、肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)和白细胞介素-12水平,以及氧化应激的组织生化参数,包括丙二醛(MDA)、髓过氧化物酶(MPO)活性、超氧化物歧化酶(SOD)活性和过氧化氢酶活性。结果PNX-14组十二指肠病变的宏观分级明显小于IND组(p<0.001)。IND组血清炎症细胞因子明显升高。PNX-14治疗显著降低了炎症细胞因子的血清水平(p<0.0001)。与IND组相比,PNX-14组的氧化成分(MDA和MPO活性)明显减少(p<0.0001),而抗氧化成分(SOD和过氧化氢酶活性)明显增多(p<0.0001)。在抑制炎症细胞因子释放和增加过氧化氢酶活性等几种抗炎特性方面,PNX-14优于FA。PNX-14对IND诱导的十二指肠溃疡形成具有显著的保护作用。这些结果表明PNX-14在治疗胃肠道炎症性疾病方面具有广阔的治疗前景。