ABSTRACT

Background: Vascular fibrosis is a universal phenomenon associated with aging, and oxidative stress plays an important role in the genesis of vascular damage in line with the aging process. However, whether antioxidants can ameliorate vascular fibrosis remains unclear.

Objectives: The present study was to determine antioxidant N-acetylcysteine (NAC) could ameliorates aortic fibrosis in aging wild-type C57BL/6 mice.

Methods: The aortas were harvested from both 12-week and 60-week wild-type mice. The 60-week mice were treated with and without the NAC for 12 weeks starting at the age of 48 weeks. Hematoxylin and eosin (H&E) staining and Masson's trichrome staining of aortic samples were performed, and the levels of reactive oxygen species (ROS), RNA expression of GAPDH, TNF-α, MCP-1, IL-6, IL-10, IL-4, SIRT-1, SIRT-3, FOXO-1, and macrophage polarization were determined.

Results: There is a positive relationship between collagen deposition and the M1/M2 macrophage ratio in the aortic wall of aged wild-type C57BL/6 mice. The higher collagen area percentage in the aortas of 60-week-old mice than in 12-week-old mice was reversed by NAC. NAC could not impact the total number of macrophages, but partly promoted M2 macrophage polarization. By performing qRT-PCR using aortic samples from these mice, we identified that SIRT-1, SIRT-3, FOXO-1 could be somehow responsible for aging-related fibrosis.

Conclusions: NAC ameliorates aortic fibrosis in aging wild type mice partly by promoting M2 macrophage polarization.

摘要

背景：血管纤维化是与衰老相关的普遍现象，氧化应激在衰老过程中血管损伤的发生中起重要作用。然而，抗氧化剂是否可以改善血管纤维化仍不清楚。

目的：本研究旨在确定抗氧化剂 N-乙酰半胱氨酸 (NAC) 能否改善衰老的野生型 C57BL/6 小鼠的主动脉纤维化。

方法：主动脉取自 12 周和 60 周的野生型小鼠。从 48 周龄开始，60 周龄小鼠接受和不接受 NAC 治疗 12 周。对主动脉样品进行苏木精和伊红（H&E）染色和Masson三色染色，检测活性氧（ROS）水平、GAPDH、TNF-α、MCP-1、IL-6、IL-10、IL的RNA表达-4、SIRT-1、SIRT-3、FOXO-1和巨噬细胞极化测定。

结果：老年野生型C57BL/6小鼠主动脉壁胶原沉积与M1/M2巨噬细胞比例呈正相关。NAC 逆转了 60 周龄小鼠主动脉中的胶原蛋白面积百分比高于 12 周龄小鼠。NAC不能影响巨噬细胞的总数，但部分促进了M2巨噬细胞极化。通过使用来自这些小鼠的主动脉样本进行 qRT-PCR，我们发现 SIRT-1、SIRT-3、FOXO-1 可能以某种方式导致与衰老相关的纤维化。

结论： NAC部分通过促进M2巨噬细胞极化来改善衰老野生型小鼠的主动脉纤维化。