Pan W-Z, Shi C-X, Tian M, Yu J-G
Department of Anesthesiology, Yantai Yuhuangding Hospital, Medical College, Qingdao University, Yantai, China.
Eur Rev Med Pharmacol Sci. 2014;18(15):2182-90.
The pathophysiology of ventilator-induced lung injury (VILI) involves multiple mechanisms including inflammation and inflammatory cells infiltration. The anti-CD11c monoclonal antibody, Efalizumab has been demonstrated to inhibit the T cell activation, migration and adhesion to keratinocytes.
In this study, we induced lung injury with mechanical ventilation in male Sprague-Dawley rats, the rats were divided into four groups: lung-protective ventilation (LV), injurious ventilation (HV), HV+human IgG control and HV+ Efalizumab groups. Then we detected the lung tissue wet/dry ratio, and the activity of myeloperoxidase (MPO) was determined. The concentration of protein, TNF-a, IL-6, IL-1b and MIP-2 in the BALF were detected by ELISA. The expression ICAM-1 was measured by Realtime PCR.
Compared with the human IgG control treated group, the treatment of Efalizumab attenuate the ventilator-induced lung injury, including the wet/dry ratio and the activity of myeloperoxidase (MPO), meanwhile, the level of pro-inflammatory cytokines, such as TNF-a, IL-6, IL-1b and MIP-2 were decreased in the BALF of Efalizumab-treated group rats compared with the human IgG-treated control group. In addition, the histopathological index of ventilator-induced lung injury was improved after efalizumab treatment, that also reduced the recruitment of inflammatory cells into the lung, such as neutrophils.
Our data suggested that Efalizumab could protect rat from ventilator-induced lung injury and improve the survival time through the inhibition of intrapulmonary inflammatory response.
呼吸机诱导性肺损伤(VILI)的病理生理学涉及多种机制,包括炎症和炎症细胞浸润。抗CD11c单克隆抗体依法利珠单抗已被证明可抑制T细胞活化、迁移以及与角质形成细胞的黏附。
在本研究中,我们对雄性Sprague-Dawley大鼠进行机械通气诱导肺损伤,将大鼠分为四组:肺保护性通气(LV)组、损伤性通气(HV)组、HV+人IgG对照组和HV+依法利珠单抗组。然后我们检测肺组织湿/干比,并测定髓过氧化物酶(MPO)的活性。通过酶联免疫吸附测定法(ELISA)检测支气管肺泡灌洗液(BALF)中蛋白质、肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)、白细胞介素-1β(IL-1β)和巨噬细胞炎性蛋白-2(MIP-2)的浓度。通过实时聚合酶链反应(Realtime PCR)测定细胞间黏附分子-1(ICAM-1)的表达。
与接受人IgG对照治疗的组相比,依法利珠单抗治疗减轻了呼吸机诱导的肺损伤,包括湿/干比和髓过氧化物酶(MPO)的活性,同时,与接受人IgG治疗的对照组相比,依法利珠单抗治疗组大鼠的BALF中促炎细胞因子如TNF-α、IL-6、IL-1β和MIP-2的水平降低。此外,依法利珠单抗治疗后呼吸机诱导性肺损伤的组织病理学指标得到改善,这也减少了炎性细胞如中性粒细胞向肺内的募集。
我们的数据表明,依法利珠单抗可通过抑制肺内炎症反应保护大鼠免受呼吸机诱导的肺损伤并延长生存时间。