ABSTRACT

Bleomycin (BLM) is a chemotherapeutic agent that can cause pulmonary fibrosis. Little is known about the possible protective role of the CB2 receptor agonist, AM1241. We investigated the effects of CB2 receptor activation by AM1241 on BLM induced lung fibrosis in a rat model. BLM was administered via the trachea. Adult female Wistar rats were divided into five groups: saline (control group), BLM (BLM group), CB2 agonist (AM1241) + BLM (BLMA group), CB2 antagonist (AM630) and CB2 agonist (AM1241) + BLM (BLMA + A group), and vehicle (dimethylsulfoxide) + BLM (BLM + vehicle group). Hydroxyproline, collagen type 1, total protein, glutathione (GSH), malondialdehyde (MDA), interleukin (IL)-6 and tumor necrosis factor (TNF)-α levels were measured in lung fibrosis and control tissue using standard methods. We investigated the histopathology of lung tissue to determine the extent of fibrosis. We found significantly higher levels of hydroxyproline, TNF-α, IL-6 and total protein in the BLM group compared to the BLMA group. The level of GSH also was higher in the BLMA group compared to the BLM group. Inflammation and fibrotic changes were significantly reduced in the BLMA group. Our findings suggest that CB2 receptor activation provided protection against BLM induced pulmonary fibrosis by suppressing oxidative stress and increasing cytokines.

摘要

博来霉素 (BLM) 是一种可导致肺纤维化的化学治疗剂。人们对 CB2 受体激动剂 AM1241 可能的保护作用知之甚少。我们研究了 AM1241 激活 CB2 受体对大鼠模型中 BLM 诱导的肺纤维化的影响。BLM 通过气管给药。成年雌性Wistar大鼠分为5组：生理盐水（对照组）、BLM（BLM组）、CB2激动剂（AM1241）+BLM（BLMA组）、CB2拮抗剂（AM630）和CB2激动剂（AM1241）+BLM（BLMA+ A 组）和媒介物（二甲亚砜）+ BLM（BLM + 媒介物组）。使用标准方法在肺纤维化和对照组织中测量羟脯氨酸、1 型胶原蛋白、总蛋白、谷胱甘肽 (GSH)、丙二醛 (MDA)、白细胞介素 (IL)-6 和肿瘤坏死因子 (TNF)-α 水平。我们研究了肺组织的组织病理学以确定纤维化的程度。我们发现与 BLMA 组相比，BLM 组的羟脯氨酸、TNF-α、IL-6 和总蛋白水平显着更高。与 BLM 组相比，BLMA 组的 GSH 水平也更高。BLMA 组的炎症和纤维化变化显着减少。我们的研究结果表明，CB2 受体激活通过抑制氧化应激和增加细胞因子，为 BLM 诱导的肺纤维化提供保护。BLMA 组的炎症和纤维化变化显着减少。我们的研究结果表明，CB2 受体激活通过抑制氧化应激和增加细胞因子，为 BLM 诱导的肺纤维化提供保护。BLMA 组的炎症和纤维化变化显着减少。我们的研究结果表明，CB2 受体激活通过抑制氧化应激和增加细胞因子，为 BLM 诱导的肺纤维化提供保护。