Liu Yuan, Lu Junyu, Wang Xiaoya, Chen Liu, Liu Su, Zhang Zhiren, Yao Wei
Department of Stomatology, Chongqing, China.
Department of Respiratory Medicine, Xinqiao Hospital, Third Military Medical University, Chongqing, China.
Cell Physiol Biochem. 2017;41(5):2037-2044. doi: 10.1159/000475434. Epub 2017 Apr 14.
Traumatic brain injury (TBI) can be complicated by TBI-triggered acute lung injury (ALI), in which inflammation plays a central role. It has been reported that an Erythropoietin-derived peptide (pHBSP) was able to ameliorate TBI; however, its function in TBI-caused ALI has not been reported yet.
In this study, we studied the effect of pHBSP on TBI-caused ALI by using a weight-drop induced TBI model. At 8 h and 24 h post-TBI, pulmonary edema (PE) and bronchoalveolar lavage fluid (BALF) proteins were measured, and haematoxylin and eosin (H&E) staining of lung sections was carried out. At 24 h following TBI, the lungs were harvested for immunofluorescence staining and qRT-PCR analysis.
At 8 h and 24 h post-TBI, pHBSP treatment significantly decreased wet/dry ratios, decreased total BALF protein, and attenuated the histological signs of pulmonary injury. At 24 h post-TBI, pHBSP treatment decreased the accumulation of CD68+ macrophages in the lung and reduced the mRNA levels of TNF-α, IL-6, IL-1β and iNOS in the lung.
We identified the protective role that pHBSP played in TBI-caused ALI, suggesting that pHBSP is a potent candidate for systemic therapy in TBI patients.
创伤性脑损伤(TBI)可并发由TBI引发的急性肺损伤(ALI),其中炎症起核心作用。据报道,一种促红细胞生成素衍生肽(pHBSP)能够改善TBI;然而,其在TBI所致ALI中的作用尚未见报道。
在本研究中,我们通过使用重物打击诱导的TBI模型,研究了pHBSP对TBI所致ALI的影响。在TBI后8小时和24小时,测量肺水肿(PE)和支气管肺泡灌洗液(BALF)蛋白,并对肺组织切片进行苏木精和伊红(H&E)染色。在TBI后24小时,采集肺组织进行免疫荧光染色和qRT-PCR分析。
在TBI后8小时和24小时,pHBSP治疗显著降低了湿/干比,降低了BALF总蛋白,并减轻了肺损伤的组织学表现。在TBI后24小时,pHBSP治疗减少了肺中CD68+巨噬细胞的积聚,并降低了肺中TNF-α、IL-6、IL-1β和iNOS的mRNA水平。
我们确定了pHBSP在TBI所致ALI中发挥的保护作用,表明pHBSP是TBI患者全身治疗的有力候选药物。