College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou 310014, China.
Department of Pharmacy, Tongde Hospital of Zhejiang Province, Hangzhou 310012, China.
Acta Biochim Biophys Sin (Shanghai). 2019 Sep 6;51(9):925-933. doi: 10.1093/abbs/gmz083.
In study, we aimed to determine the mechanisms underlying the gastroprotective effects of sodium copper chlorophyllin (SCC) against ethanol-induced gastric ulcer injury in mice. First, the gastroprotective effects of SCC against gastric ulcer induced by ethanol were assessed. Then, biochemical, histopathological, immunohistochemistry assays, and western blot analysis were conducted to determine the possible mechanisms of action underlying the effects of SCC. Compared to the effects of omeprazole (OME) in a confirmed mouse model of ethanol-induced gastric ulcer injury, treatment with various doses of SCC resulted in up-regulation of Bcl-2 and down-regulation of the pro-apoptotic protein Bax. Significant decreases in the levels of the malondialdehyde (MDA), myeloperoxidase (MPO), and NO in the gastric tissues were observed. Furthermore, inflammatory cytokine analysis revealed that SCC treatment inhibited the expressions of TNF-α and IL-6, greatly reduced the phosphorylation level of IκB, and repressed the nuclear translocation of NF-κB p65, which demonstrated that SCC inhibited the activation of the NF-κB pathway. The present findings suggest that the protective effects of SCC may be beneficial as a potential preventive and therapeutic agent for gastric ulcer through the NF-κB pathway. Taken together, SCC administration significantly decreased the levels of MPO, NO, and MDA in gastric tissue and exerted a powerful anti-inflammatory activity as demonstrated by reduction in the secretions of proinflammatory mediators such as IL-6 and TNF-α in the serum of mice exposed to ethanol.
在这项研究中，我们旨在确定叶绿素铜钠盐（SCC）对乙醇诱导的小鼠胃溃疡损伤的胃保护作用的机制。首先，评估了 SCC 对乙醇诱导的胃溃疡的胃保护作用。然后，进行了生化、组织病理学、免疫组织化学测定和 Western blot 分析，以确定 SCC 作用的可能机制。与奥美拉唑（OME）在乙醇诱导的胃溃疡损伤的确认小鼠模型中的作用相比，用各种剂量的 SCC 治疗导致 Bcl-2 的上调和促凋亡蛋白 Bax 的下调。胃组织中丙二醛（MDA）、髓过氧化物酶（MPO）和 NO 的水平显著降低。此外，炎症细胞因子分析表明，SCC 治疗抑制 TNF-α 和 IL-6 的表达，大大降低 IκB 的磷酸化水平，并抑制 NF-κB p65 的核转位，表明 SCC 抑制了 NF-κB 途径的激活。这些发现表明，SCC 的保护作用可能有益于通过 NF-κB 途径作为预防和治疗胃溃疡的潜在药物。总之，SCC 给药可显著降低胃组织中 MPO、NO 和 MDA 的水平，并通过减少乙醇暴露小鼠血清中促炎介质如 IL-6 和 TNF-α 的分泌来发挥强大的抗炎活性。
