Song Qing, Zhou Zi-Jing, Cai Shan, Chen Yan, Chen Ping
Department of Respiratory and Critical Care Medicine, the Second Xiangya Hospital, Central South University, Changsha, China.
Research Unit of Respiratory Disease, Central South University, Changsha, China.
Int J Environ Health Res. 2022 Aug;32(8):1745-1755. doi: 10.1080/09603123.2021.1910211. Epub 2021 Apr 7.
This study was to investigate the effects of oxidative stress in cigarette smoke (CS)-induced cell apoptosis in mice with emphysema. Thirty-two mice were divided into four groups: the control group, the CS group, the CS + Pifithrin-α group, and the CS + NAC group. Pathological changes and apoptosis in lung tissue of mice were detected. The activity of malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), and total antioxidant capacity (T-AOC) were measured using spectrophotometer. The proteins expression of p53, Bcl-2, Bax, and caspase-3 were determined by western blot. The results showed that cell apoptosis, lung structural damage, and the activity of MDA, as well as the expression of apoptosis-related proteins Bax, total caspase-3, and cleaved caspase-3 were increased in CS-treated mice. The activity of SOD, CAT, and T-AOC, as well as the expression of anti-apoptosis protein Bcl-2 were decreased in CS-treated mice when compared with the control group. However, Pifithrin-α (p53 inhibitor) and N-Acetylcysteine (NAC) could reduce cell apoptosis, lung structural damage and oxidative stress, accelerate the expression of Bcl-2, while suppressing the expression of Bax, total caspase-3 and cleaved caspase-3. More importantly, the treatment with NAC even inhibited the expression of p53. In conclusions, oxidative stress linking the p53 is involved in cell apoptosis in CS-treated emphysema mice.
本研究旨在探讨氧化应激在香烟烟雾(CS)诱导的肺气肿小鼠细胞凋亡中的作用。32只小鼠分为四组:对照组、CS组、CS + 匹莫苯丹-α组和CS + N-乙酰半胱氨酸(NAC)组。检测小鼠肺组织的病理变化和细胞凋亡情况。使用分光光度计测量丙二醛(MDA)、超氧化物歧化酶(SOD)、过氧化氢酶(CAT)的活性和总抗氧化能力(T-AOC)。通过蛋白质印迹法测定p53、Bcl-2、Bax和半胱天冬酶-3的蛋白表达。结果显示,CS处理的小鼠细胞凋亡、肺结构损伤、MDA活性以及凋亡相关蛋白Bax、总半胱天冬酶-3和裂解的半胱天冬酶-3的表达均增加。与对照组相比,CS处理的小鼠SOD、CAT和T-AOC的活性以及抗凋亡蛋白Bcl-2的表达均降低。然而,匹莫苯丹-α(p53抑制剂)和N-乙酰半胱氨酸(NAC)可减少细胞凋亡、肺结构损伤和氧化应激,促进Bcl-2的表达,同时抑制Bax、总半胱天冬酶-3和裂解的半胱天冬酶-3的表达。更重要的是,NAC处理甚至抑制了p53的表达。总之,与p53相关的氧化应激参与了CS处理的肺气肿小鼠的细胞凋亡。