School of Pharmacy, Anhui University of Chinese Medicine, Hefei, Anhui 230012, China.
Drug Clinical Trial Institution, Wannan Medical College Yijishan Hospital, Wuhu, Anhui 241001, China; Hefei Cancer Hospital, Chinese Academy of Sciences, Hefei, Anhui 230012, China.
Int Immunopharmacol. 2021 Dec;101(Pt B):108373. doi: 10.1016/j.intimp.2021.108373. Epub 2021 Nov 19.
Allyl isothiocyanate(AITC) has been shown to play an important role in the improved symptoms of chronic obstructive pulmonary disease(COPD) and the inhibition of inflammation, but the role in COPD lipid metabolism disorder and the molecular mechanism remains unclear. We aimed to explore whether and how AITC affects COPD by regulating lipid metabolism and inflammatory response.
The COPD rat model was established by cigarette smoke exposure. Cigarette smoke extract stimulated 16HBE cells to induce a cell model. The effect of AITC treatment was detected by lung function test, H&E staining, Oil red O staining, immunohistochemistry, ELISA, CCK-8, HPLC, fluorescence efflux test, siRNA, RT-PCR, and Western blotting. Biological analysis was performed to analyze the results. Graphpad Prism 8.0 software was used for statistical analysis.
AITC can improve lung function and pathological injury in COPD rats. The levels of IL-1 β and TNF- α in the AITC treatment group were significantly lower than those in the model group(P < 0.05), and the lipid metabolism was also improved (P < 0.05). AITC reverses CSE-induced down-regulation of LXR α, ABCA1, and ABCG1 expression and function in a time-and concentration-dependent manner (P < 0.05). AITC regulates the cholesterol metabolism disorder induced by CSE in NR8383 cells and attenuates macrophage inflammation (P < 0.05). In addition, after silencing LXR α with siRNA, the effect of AITC was also inhibited.
These results suggest that AITC improves COPD by promoting RCT process and reducing inflammatory response via activating LXR pathways.
丙烯基异硫氰酸酯（AITC）已被证明在改善慢性阻塞性肺疾病（COPD）症状和抑制炎症方面发挥重要作用，但在 COPD 脂质代谢紊乱中的作用及其分子机制尚不清楚。我们旨在探讨 AITC 是否以及如何通过调节脂质代谢和炎症反应来影响 COPD。
通过香烟烟雾暴露建立 COPD 大鼠模型。香烟烟雾提取物刺激 16HBE 细胞诱导细胞模型。通过肺功能试验、H&E 染色、油红 O 染色、免疫组织化学、ELISA、CCK-8、HPLC、荧光外排试验、siRNA、RT-PCR 和 Western blotting 检测 AITC 处理的效果。采用生物分析软件分析结果。Graphpad Prism 8.0 软件进行统计分析。
AITC 可改善 COPD 大鼠的肺功能和病理损伤。AITC 治疗组的 IL-1β和 TNF-α水平明显低于模型组（P<0.05），脂质代谢也得到改善（P<0.05）。AITC 以时间和浓度依赖的方式逆转 CSE 诱导的 LXRα、ABCA1 和 ABCG1 表达和功能下调（P<0.05）。AITC 调节 CSE 诱导的 NR8383 细胞胆固醇代谢紊乱，减轻巨噬细胞炎症（P<0.05）。此外，用 siRNA 沉默 LXRα 后，AITC 的作用也被抑制。
这些结果表明，AITC 通过激活 LXR 通路促进 RCT 过程和减轻炎症反应来改善 COPD。
