单肺通气导致的肺炎性损伤及姜黄素的干预作用

【目的】 探讨姜黄素预先给药对兔单肺通气导致的肺炎性损伤的影响及可能机制。【方法】 将12只健康新西兰白兔随机分为2组,每组6只:开胸单肺通气+对照剂组(组1)和开胸单肺通气+姜黄素组(组2)。两组兔经腹腔注射分别预先给予对照剂和姜黄素,每天早晚各1次。连续给药7 d后,两组兔均经口插入单腔气管导管行右侧单肺通气,并左胸开一小口模拟手术操作。分别于机械通气前(T0)及实验结束前(T4)采集动脉血行血气分析,计算氧合指数。处死动物后,行右侧支气管肺泡灌洗测定髓过氧化物酶 (MPO)含量及中性粒细胞数量;取左侧肺组织,观察病理学结果并行肺损伤评分;采用ELISA法分别检测左右侧肺组织匀浆中白细胞介素-8(IL-8)、IL-10、IL-1β、肿瘤坏死因子α(TNF-α)、巨噬细胞炎性蛋白-1 (MIP-1)的含量;采用免疫组化法检测左侧肺组织中核因子-κB(NF-κB), 髓样分化因子88(MyD88)和Toll样受体2(TLR2)的 表达。【结果】 T4时组2氧合指数较组1显著升高(P < 0.05)。与组1比较,组2支气管肺泡灌洗液中MPO含量、中性粒细胞计数、肺损伤评分、肺组织匀浆中IL-8、IL-1β、TNF-α、MIP-1含量均降低,IL-10含量升高(P < 0.05)。同组内两侧肺比较,组1非通气侧肺炎性损伤更严重(P < 0.05),组2无差异(P > 0.05)。 与组1比较,组2肺组织中NF-κB, MyD88和TLR2的 表达明显减少。【结论】姜黄素预先给药显著抑制开胸手术单肺通气时炎性因子的释放,减轻肺炎性损伤,其机制可能与TLR2通过MyD88信号通路调节NF-κB的活性有关。

Mechanism of Lung Inflammatory Injury Induced by One-lung Ventilation and Effects of Curcumin in a Rabbit Model of Thoracic Surgery

【Objective】 To investigate the effect and mechanism of curcumin on lung inflammatory injury induced by one-lung ventilation (OLV) in a rabbit model of thoracic surgery. 【Methods】 Twelve New Zealand rabbits weighing 2.0~2.5 kg were randomly allocated into two groups (n = 6 each): OLV+placebo group (group 1) received 10% dimethyl sulfoxide (DMSO) as placebo and OLV+curcumin group (group 2) received curcumin 40 mg/kg which dissolvedin 10% DMSO by intraperitoneal injection. After seven consecutive days of pretreatment, the animals were received orotracheal intubation and the model of OLV-induced lung injury in thoracic surgery was established. Then two groups were received mechanical ventilation (VT = 12 mL/kg, RR = 40 bpm, I:E = 1:2, FiO2= 0.6). After two lung ventilation (TLV) for 30 min, they received OLV for 3 h, and then turned to TLV for 30 min. Monitoring blood pressure, heart rate and peak inspiratory pressure of animals in two groups continuously, and collecting arterial blood samples to calculate the PaO2/FiO2 ratio (P/F ratio) before (T0) and after (T4) mechanical ventilation, respectively. At the end of the experiment, the animals were killed and abronchoalveolar lavage was performed in the right lung lobes for the concentration of MPO and neutrophil counts. The left lobes were collected for HE stain to observe pathological morphological changes and get lung injury score. Then the concentration of IL-8, IL-10, IL-1β, TNF-α, and MIP-1 (macrophage inflammatory protein-1) in two lungs were quantified using enzyme-linked immunosorbent assay (ELISA). Furthermore, the levels of nuclear factor kappa B (NF-κB), myeloid differentiation factor 88 (MyD88) and Toll-like receptor 2 (TLR2) were analyzed by immunohistochemistry.【Results】 The P/F ratio in group 2 was significantly higher than that in group 1 at T4 (P < 0.05). Compared with group 1, the concentration of MPO and neutrophil counts in BALF, lung injury score, the contents of IL-8, IL-1β, TNF-α, and MIP-1 in group 2 were significantly lower (P < 0.05), the level of IL-10 in group 2 was significantly higher (P < 0.05). In group 1, compared with the right (ventilated) lung, MPO concentration in BALF, neutrophil counts, lung injury score and the contents of IL-8, IL-1β, TNF-α, and MIP-1 in the left (nonventilated) lung were significantly higher(P < 0.05), and the contents of IL-10 in the left lung were lower (P < 0.05). The expression of NF-κB, MyD88, and TLR2 in the group 2 were much lower than those in the group 1 (P < 0.05). 【Conclusion】Curcumin pretreatment attenuates inflammatory injury induced by one lung ventilation of rabbits in thoracic surgery, and the anti-inflammatory effect of curcumin is possibly related to the inhibition of TLR2, MyD88, and NF-κB.