Deng JiuLing, He YuQiong, Sun GuangChun, Yang Hong, Wang Liang, Tao Xia, Chen WanSheng
Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China; Department of Pharmacy, Shanghai Fifth People's Hospital, Fudan University, Shanghai, 200240, China.
Department of Pharmacy, Changzheng Hospital, Second Military Medical University, Shanghai, 200003, China.
J Ethnopharmacol. 2023 Apr 6;305:116071. doi: 10.1016/j.jep.2022.116071. Epub 2022 Dec 27.
Idiopathic pulmonary fibrosis (IPF), characterized by excessive collagen deposition, is a progressive and typically fatal lung disease without effective therapeutic methods. Tanreqing injection (TRQ), a Traditional Chinese Patent Medicine, has been widely used to treat inflammatory respiratory diseases clinically.
The present work aims to elucidate the therapeutic effects and the possible mechanism of TRQ against pulmonary fibrosis.
The pulmonary fibrosis murine model were constructed by the intratracheal injection of bleomycin (BLM). 7 days later, TRQ-L (2.6 ml/kg) and TRQ-H (5.2 ml/kg) were administered via intraperitoneal injection respectively for 21 days. The efficacy and underlying molecular mechanism of TRQ were investigated.
Here, we showed that TRQ significantly inhibited BLM-induced lung edema and pulmonary function. TRQ markedly reduced BLM-promoted inflammatory cell infiltration in BALF and inflammatory cytokines release (TNF-α, IL-6, and IL-1β) in serum and lung tissues. Meanwhile, TRQ also alleviated BLM-induced collagen synthesis and deposition. Simultaneously, TRQ attenuated BLM-induced pulmonary fibrosis through regulating the expression of fibrotic hallmarks, manifested by down-regulated α-SMA and up-regulated E-cadherin. Moreover, we found that TRQ significantly prevented STING, p-P65, BIP, p-PERK, p-eIF2α, and ATF4 expression in lung fibrosis mice.
Taken together, our results indicated that TRQ positively affects inflammatory responses and lung fibrosis by regulating STING-mediated endoplasmic reticulum stress (ERS) signal pathway.
特发性肺纤维化(IPF)以胶原蛋白过度沉积为特征,是一种进行性且通常致命的肺部疾病,尚无有效的治疗方法。痰热清注射液(TRQ)是一种中成药,已在临床上广泛用于治疗炎症性呼吸道疾病。
本研究旨在阐明痰热清注射液对肺纤维化的治疗作用及其可能的机制。
通过气管内注射博来霉素(BLM)构建肺纤维化小鼠模型。7天后,分别通过腹腔注射给予低剂量痰热清注射液(TRQ-L,2.6 ml/kg)和高剂量痰热清注射液(TRQ-H,5.2 ml/kg),持续21天。研究痰热清注射液的疗效及其潜在的分子机制。
在此,我们表明痰热清注射液显著抑制博来霉素诱导的肺水肿和肺功能。痰热清注射液显著减少了博来霉素促进的支气管肺泡灌洗液(BALF)中的炎性细胞浸润以及血清和肺组织中炎性细胞因子(TNF-α、IL-6和IL-1β)的释放。同时,痰热清注射液还减轻了博来霉素诱导的胶原蛋白合成和沉积。此外,痰热清注射液通过调节纤维化标志物的表达减轻了博来霉素诱导的肺纤维化,表现为α-SMA下调和E-钙黏蛋白上调。此外,我们发现痰热清注射液显著抑制了肺纤维化小鼠中STING、p-P65、BIP、p-PERK、p-eIF2α和ATF4的表达。
综上所述,我们的结果表明痰热清注射液通过调节STING介导的内质网应激(ERS)信号通路对炎症反应和肺纤维化产生积极影响。