Yang Zhenyu, Ji Wei, Li Ming, Qi Zhidong, Huang Rui, Qu Jingdong, Wang Hongliang, Wang Huaiquan
Intensive Care Unit, The Second Affiliated Hospital of Harbin Medical University Harbin, Heilongjiang Province, China.
Department of General Surgery, The Second Affiliated Hospital of Harbin Medical University Harbin, Heilongjiang Province, China.
Am J Transl Res. 2019 Sep 15;11(9):6024-6031. eCollection 2019.
The study was designed to investigate the effect of Nimesulide (NIM) on acute lung injury (ALI) in mice with severe acute pancreatitis (SAP). In our study, caerulein and LPS were employed to establish the ALI mice model induced by SAP. All animals were divided into four groups randomly: control, model (SAP), NIM low and high dosages groups. Following treatment with NIM, histopathology observation of pancreatic tissues and lung tissues were detected by hematoxylin and eosin (H&E) staining. The levels of serum amylase, lipase, tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β) and IL-6 were measured by ELISA. The ratio of wet lung to dry lung (W/D) was calculated. In addition, the expression levels of TNF-α, IL-1β and IL-6 were measured by Western blotting. Moreover, the expression of cyclooxygenase-2 (COX-2) was detected using Immunohistochemistry analysis. The results revealed that NIM markedly improved pancreatic histological injury and decreased the levels of serum amylase, lipase, TNF-α, IL-1β and IL-6 in a dose-dependent after NIM treatment. For ALI induced by SAP, pulmonary edema were significantly alleviated compared with the mice in SAP group. In addition, the decreased ratio of W/D were observed after NIM intervene. The expression levels of TNF-α, IL-1β and IL-6 proteins were downregulated following NIM treatment. More, NIM inhibited the expression of COX2 in lung tissues. Taken together, our study demonstrated that NIM was able to protect against ALI induced by SAP via inhibiting inflammation, which will be of novel therapeutic strategies for the clinical treatment of ALI.
本研究旨在探讨尼美舒利(NIM)对重症急性胰腺炎(SAP)小鼠急性肺损伤(ALI)的影响。在我们的研究中,采用蛙皮素和脂多糖建立SAP诱导的ALI小鼠模型。所有动物随机分为四组:对照组、模型组(SAP)、NIM低剂量组和高剂量组。NIM治疗后,通过苏木精-伊红(H&E)染色对胰腺组织和肺组织进行组织病理学观察。采用酶联免疫吸附测定(ELISA)法检测血清淀粉酶、脂肪酶、肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(IL-1β)和IL-6的水平。计算肺湿重与干重之比(W/D)。此外,通过蛋白质印迹法检测TNF-α、IL-1β和IL-6的表达水平。而且,采用免疫组织化学分析法检测环氧化酶-2(COX-2)的表达。结果显示,NIM治疗后能显著改善胰腺组织学损伤,并呈剂量依赖性降低血清淀粉酶、脂肪酶、TNF-α、IL-1β和IL-6的水平。对于SAP诱导的ALI,与SAP组小鼠相比,肺水肿明显减轻。此外,NIM干预后观察到W/D比值降低。NIM治疗后TNF-α、IL-1β和IL-6蛋白的表达水平下调。此外,NIM抑制肺组织中COX2的表达。综上所述,我们的研究表明NIM能够通过抑制炎症来预防SAP诱导的ALI,这将为ALI的临床治疗提供新的治疗策略。