Department of Respiratory Medicine, Guizhou Provincial People's Hospital, No. 83, Zhongshan East Road, Guiyang, Guizhou, China.
NHC Key Laboratory of Pulmonary Immunological Diseases, Guizhou Provincial People's Hospital, Guiyang, Guizhou, China.
Eur J Med Res. 2023 Oct 25;28(1):460. doi: 10.1186/s40001-023-01396-w.
Hypomethylation of the perforin gene promoter in CD4 + T cells, inflammation and oxidative stress, might be involved in alveolar septal cell apoptosis associated with emphysema in rats. This study aimed to investigate the effects of S-adenosylmethionine (SAM) on this kind of apoptosis in rats with autoimmune emphysema.
Twenty-four rats were randomly divided into three groups: a normal control group, a model group, and a SAM group. Pathological changes in lung tissues were observed, and the mean linear intercept (MLI) and mean alveolar number (MAN) were measured. The levels of anti-endothelial cell antibodies (AECA) in serum, alveolar septal cell apoptosis, perforin gene promotor methylation in CD4 + T cells in the spleen, and the levels of cytokines, malondialdehyde (MDA), and glutathione (GSH) and the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in bronchoalveolar lavage fluid (BALF) were investigated.
The MLI, apoptosis index (AI) of alveolar septal cells, levels of AECA in serum, and levels of tumour necrosis factor-α (TNF-α), matrix metalloproteinase-9 (MMP-9) and MDA in BALF were increased, while the MAN, methylation levels, and the activities of GSH, SOD and GSH-Px in BALF were decreased in the model group compared with those in the normal control group and the SAM group (all P < 0.05). The levels of interleukin-8 (IL-8) in BALF were greater in the model group than in the normal control group (P < 0.05).
SAM protects against alveolar septal cell apoptosis, airway inflammation and oxidative stress in rats with autoimmune emphysema possibly by partly reversing the hypomethylation of the perforin gene promoter in CD4 + T cells.
CD4+T 细胞穿孔素基因启动子的低甲基化、炎症和氧化应激，可能与大鼠肺气肿肺泡间隔细胞凋亡有关。本研究旨在探讨 S-腺苷甲硫氨酸（SAM）对自身免疫性肺气肿大鼠这种细胞凋亡的影响。
24 只大鼠随机分为三组：正常对照组、模型组和 SAM 组。观察肺组织的病理变化，测量平均线性截距（MLI）和平均肺泡数（MAN）。检测血清抗内皮细胞抗体（AECA）水平、肺泡间隔细胞凋亡、脾 CD4+T 细胞穿孔素基因启动子甲基化、支气管肺泡灌洗液（BALF）中细胞因子、丙二醛（MDA）和谷胱甘肽（GSH）水平及超氧化物歧化酶（SOD）和谷胱甘肽过氧化物酶（GSH-Px）活性。
与正常对照组和 SAM 组相比，模型组 MLI、肺泡间隔细胞凋亡指数（AI）、血清 AECA 水平以及 BALF 中肿瘤坏死因子-α（TNF-α）、基质金属蛋白酶-9（MMP-9）和 MDA 水平升高，而 MAN、BALF 中 GSH、SOD 和 GSH-Px 水平以及穿孔素基因启动子甲基化水平降低（均 P<0.05）。与正常对照组相比，模型组 BALF 中白细胞介素-8（IL-8）水平升高（P<0.05）。
SAM 可防止自身免疫性肺气肿大鼠肺泡间隔细胞凋亡、气道炎症和氧化应激，可能部分通过逆转 CD4+T 细胞穿孔素基因启动子的低甲基化。
