| 李 宏,阳 甜,陈天君,庞亚梅,杨 岚.脂蛋白受体激动剂调节COPD小鼠炎症反应机制研究[J].,2020,(12):2234-2238 |
| 脂蛋白受体激动剂调节COPD小鼠炎症反应机制研究 |
| Lipoprotein Receptor Agonist Regulates the Inflammatory Response of COPD Mice |
| 投稿时间：2020-02-18 修订日期：2020-03-12 |
| DOI：10.13241/j.cnki.pmb.2020.12.007 |
| 中文关键词: COPD 炎症反应 脂蛋白受体激动剂 活性氧 |
| 英文关键词: COPD Inflammatory response Lipoprotein receptor agonist Reactive oxygen species |
| 基金项目:陕西省自然科学基础研究计划项目（2018JQ8040） |
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| 中文摘要: |
| 摘要 目的：探究脂蛋白受体激动剂BML-111调节COPD小鼠炎症反应的机制。方法：构建COPD小鼠模型，通过HE染色检测小鼠肺组织和血管周围炎性细胞侵润程度；通过ELISA检测小鼠支气管肺泡灌洗液（BALF）中TGF-β、TNF-α、IL-1β和IL-10的含量；通过Western blot检测小鼠肺组织中NLRP3、Cleaved-IL-1β、Cleaved-caspase-1和Nrf-2的表达。结果：番红染色结果显示，与对照组相比，COPD模型组显示出严重的炎症反应，炎症细胞侵润程度增加，肺泡囊和间隙增大，支气管壁增厚。与模型组相比，低BML、高BML和Dex组的肺组织和血管周围的炎性细胞浸润程度明显降低(P<0.05)。ELISA检测结果显示，COPD模型组中TGF-β、TNF-α、IL-10和IL-1β的表达均明显高于对照组(P<0.05)；在高BML组中，TGF-β、TNF-α、IL-10和IL-1β的表达明显低于COPD模型组中的表达(P<0.05)。与COPD模型组相比，Dex组的TNF-α、IL-10和IL-1β的表达显著下调(P<0.05)，TGF-β的表达无显著差异(P>0.05)。Western blot检测结果显示，与对照组相比，COPD模型组中NLRP3、cleaved-IL-1β和cleaved-caspase-1的表达显著上调(P<0.05)；与COPD模型组相比，低剂量BML组、高剂量BML组和Dex组中NLRP3、cleaved-IL-1β和cleaved-caspase-1的表达显著下调(P<0.05)。活性检测结果显示，与对照组相比，COPD模型组的SOD活性显著降低(P<0.05)，MDA活性显著增强(P<0.05)。BML-111处理后，与模型组相比，10 mg/ kg的BML-111和2 mg/ kg的Dex显著提高SOD活性，并显著降低MDA活性(P<0.05)。与对照组相比，COPD模型组的Nrf-2的表达显著下调；而低剂量BML组，高剂量BML组和Dex组中Nrf-2的表达明显高于COPD模型组(P<0.05)。结论：BML-111对COPD小鼠的抗炎作用可能是通过调节NLRP3炎症小体激活和ROS的产生来介导。 |
| 英文摘要: |
| ABSTRACT Objective: Investigate the mechanism of lipoprotein receptor agonist BML-111 regulating the inflammatory response in COPD mice. Methods: Modelling of COPD mice was established. The degree of inflammatory cell invasion in the lung tissue and surrounding blood vessels was detected by HE staining. The contents of TGF-β, TNF-α, IL-1β and IL-10 in bronchoalveolar lavage fluid (BALF) of mice were detected by ELISA. The expressions of NLRP3, Cleaved-IL-1β, Cleaved-caspase-1 and Nrf-2 in lung tissue of mice were detected by Western blot. Results: Saffron staining results showed that compared with the control group, the COPD model group showed a severe inflammatory response, increased inflammatory cell invasion, increased alveolar sacs and spaces, and thickened bronchial walls. Compared with the model group, the levels of inflammatory cells in the lung tissue and blood vessels around the low BML, high BML, and Dex groups were significantly reduced (P<0.05). ELISA results showed that the expressions of TGF-β, TNF-α, IL-10 and IL-1β in the COPD model group were significantly higher than those in the control group; in the high BML group, the expressions of TGF-β, TNF-α, IL-10 and IL-1β were significantly lower than those in the COPD model group (P<0.05). Compared with the COPD model group, the expressions of TNF-α, IL-10 and IL-1β in the Dex group were significantly down-regulated (P<0.05), while the expressions of TGF-β was not significantly different (P>0.05). Western blot results showed that compared with the control group, the expressions of NLRP3, cleaved-IL-1β and cleaved-caspase-1 in the COPD model group were significantly up-regulated (P<0.05). And compared with the COPD model group, the expressions of NLRP3, cleaved-IL-1β, and cleaved-caspase-1 in the low-dose BML group, the high-dose BML group, and the Dex group were significantly down-regulated (P<0.05). Activity test results showed that compared with the control group, the SOD activity of the COPD model group was significantly reduced (P<0.05), but the MDA activity was significantly enhanced (P<0.05). After BML-111 treatment, compared with the model group, 10 mg/kg BML-111 and 2 mg/kg Dex significantly increased SOD activity and significantly reduced MDA activity (P<0.05). In addition, compared with the control group, the expression of Nrf-2 in the COPD model group was significantly down-regulated; while the expression of Nrf-2 in the low-dose BML group, the high-dose BML group and the Dex group was significantly higher than in the COPD model group (P<0.05). Conclusion: The anti-inflammatory effect of BML-111 on COPD mice may be mediated by regulating NLRP3 inflammatory body activation and ROS production. |
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