Zhu Guoying, Chen Li, Liu Su, She Ling, Ding Yongnian, Yang Changqing, Zhu Fengshang
Department of Clinical Nutrition, Putuo People's Hospital, School of Medicine, Tongji University, Shanghai, 200060, China.
Department of Gastroenterology, Tongji Hospital, School of Medicine, Tongji University, Shanghai, 200065, China.
Heliyon. 2022 Jul 5;8(7):e09872. doi: 10.1016/j.heliyon.2022.e09872. eCollection 2022 Jul.
Pharmacological inhibition of cyclooxygenase-2 (COX-2) activity ameliorated the severity of non-alcoholic steatohepatitis (NASH) rats. It is not completely understood that the role of COX-2 inhibitor celecoxib on adiponectin receptors (Adipo-R1/R2) expression in different tissues in NASH rats. Sprague-Dawley male NASH rats induced by a high-fat diet (HFD) were administrated with or without celecoxib for 8 weeks. Biochemical parameters of liver function, glucose, and lipid metabolism, and the levels of adiponectin, tumor necrosis factor-alpha (TNF-α), prostaglandin E (PGE) in the serum or liver were collected according to the standard protocols. The mRNA and protein levels of Adipo-R1, Adipo-R2, and COX-2 in the liver, muscle, and visceral fat were performed by quantitative real-time polymerase chain reaction (q-PCR) and Western blot analysis, respectively The results showed that celecoxib ameliorated the various clinical indicators and pathological characteristics in the NASH rats, including body weight, liver function, liver index, and redox activities in serum and hepatic samples. The serum concentrations of adiponectin and TNF-α and PGE were negatively correlated. As expected, these ameliorative effects of celecoxib were associated with the gene and protein levels up-regulation of Adipo-R1, Adipo-R2 in the liver and visceral fat tissues, and seeming to be compensatory down-regulation expression in muscle tissues ( <0.05). Additionally, COX-2 protein expression was negatively correlated with serum adiponectin levels, protein expression of adiponectin receptors from the liver and visceral fat, conversely, positively correlated with those from the muscle. Our current study demonstrate that celecoxib might effectively alleviate NASH rats in a unique manner closely relevant to redistributing the expression of adiponectin receptors in the liver, visceral fat, and muscle. However, the precise molecular mechanism needs further study.
环氧化酶-2（COX-2）活性的药理学抑制改善了非酒精性脂肪性肝炎（NASH）大鼠的病情严重程度。COX-2抑制剂塞来昔布对NASH大鼠不同组织中脂联素受体（Adipo-R1/R2）表达的作用尚未完全明确。将高脂饮食（HFD）诱导的Sprague-Dawley雄性NASH大鼠分为两组，一组给予塞来昔布，另一组不给予，持续给药8周。按照标准方案收集肝功能、血糖和脂质代谢的生化参数，以及血清或肝脏中脂联素、肿瘤坏死因子-α（TNF-α）、前列腺素E（PGE）的水平。分别通过定量实时聚合酶链反应（q-PCR）和蛋白质免疫印迹分析检测肝脏、肌肉和内脏脂肪中Adipo-R1、Adipo-R2和COX-2的mRNA和蛋白质水平。结果显示，塞来昔布改善了NASH大鼠的各种临床指标和病理特征，包括体重、肝功能、肝脏指数以及血清和肝脏样本中的氧化还原活性。血清脂联素、TNF-α和PGE浓度呈负相关。正如预期的那样，塞来昔布的这些改善作用与肝脏和内脏脂肪组织中Adipo-R1、Adipo-R2的基因和蛋白质水平上调有关，而在肌肉组织中似乎是代偿性下调表达（<0.05）。此外，COX-2蛋白表达与血清脂联素水平、肝脏和内脏脂肪中脂联素受体的蛋白表达呈负相关, 相反，与肌肉中的脂联素受体蛋白表达呈正相关。我们目前的研究表明，塞来昔布可能以一种独特的方式有效减轻NASH大鼠的病情，这种方式与肝脏、内脏脂肪和肌肉中脂联素受体表达的重新分布密切相关。然而，确切的分子机制需要进一步研究。
