Protectin DX 对老年大鼠肺损伤相关炎性因子和氧化损伤的保护作用

目的 初步探讨 Protectin DX (保护素 DX,PDX)对老年大鼠肺叶切除术后肺损伤相关炎性介质及氧化因子的调控及保护作用。 方法 将 30 只 SPF 级健康的老年雄性 SD 大鼠(10 月龄)随机分为假手术组( n = 10) 、手术组( n = 10) 、PDX 处理组( n = 10) 。 假手术组和手术组在造模 1 h 后腹腔注射 300 μL 生理盐水,PDX 处理组于造模1 h 后腹腔注射 300 μL PDX(500 ng) 。 将所有大鼠于造模 24 h 后采用过度麻醉的方法处死,收集标本。 采用 HE染色观察各组肺标本病理形态变化,评价各组大鼠肺标本的干湿质量比( W / D) ;检测肺泡灌洗液中蛋白浓度及相关炎症因子的含量;检测肺组织中 MDA、ROS、SOD 的含量以及 HO-1、核因子 NF-κB 的蛋白表达量。 结果 假手术组肺组织结构清晰,未见炎症细胞浸润;手术组老年大鼠肺组织结构紊乱,伴有大量炎症细胞浸润;PDX 处理组大鼠肺组织结构不清晰,存在少量的炎症细胞浸润。 与假手术组相比较,手术组老年大鼠肺损伤评分及肺组织 W / D显著增高( P<0. 01) ,肺泡灌洗液中蛋白浓度及 IL-1β、IL-6 和 TNF-α 含量明显增加( P< 0. 01) ,肺组织中 MDA、ROS含量及 NF-κB 蛋白表达显著升高,SOD 活性及 HO-1 蛋白表达明显降低( P< 0. 05) 。 与手术组相比较,PDX 处理组老年大鼠肺损伤评分及肺组织 W / D 显著降低( P<0. 01) ,肺泡灌洗液中蛋白浓度及 IL-1β、IL-6 和 TNF-α 含量明显下降( P<0. 01) ,肺组织中 MDA、ROS 含量及 NF-κB 蛋白表达显著降低,SOD 活性及 HO-1 蛋白表达明显升高( P <0. 05) 。 结论 PDX 能够明显减低老年大鼠肺叶切除术后的肺损伤程度,这种作用可能与其调节肺组织中 HO-1、NF-κB 蛋白的表达从而抑制肺部的氧化应激反应和炎症反应相关。

Protectin DX Protects Lung Injury-related Inflammatory Factors andOxidative Damage in Aged Rats

Objective The role of Protectin DX ( PDX) in the regulation and protection of inflammatory mediatorsand oxidative factors related to lung injury after lobectomy in elderly rats was explored. Method Thirty healthyelderly male SD rats (10 months old) were randomly divided into the sham operation group, the surgery group andthe PDX treatment group ( n = 10) . In the sham operation group and the operation group, 300 μL of physiologicalsaline was injected intraperitoneally 1 hour after the modeling, and in the PDX treatment group, 300 μL of PDX(500 ng) was intraperitoneally injected 1 hour after the modeling. All rats were sacrificed by over-anaesthesia 24 hafter modeling, and specimens were collected. The pathological changes of lung samples in each group wereobserved with HE staining, and the dry-wet mass ratio ( W / D) of lung samples in each group was evaluated. Theprotein concentration in the bronchoalveolar lavage fluid ( BALF ) was detected; the inflammation factors in theBALF was detected; the content of MDA, SOS, SOD and the expression of HO-1, nuclear factor ( NF) -κB proteinin lung tissue were detected. Result The lung tissue structure of the sham operation group was clear, and noinflammatory cell infiltration was seen; the lung tissue structure of the elderly rats in the operation group wasdisordered, accompanied by a large number of inflammatory cell infiltration. Compared with the sham operationgroup, the lung injury score and lung tissue W / D of the elderly rats in the operation group were significantlyincreased ( P < 0. 01) . The protein concentration and the contents of IL-1β, IL-6 and TNF-α in alveolar lavagefluid were significantly increased ( P<0. 01) , and the levels of MDA, ROS and NF-κB protein in lung tissues weresignificantly increased, SOD activity and HO- 1 protein expression was significantly reduced ( P<0. 05) . Comparedwith the surgery group, the lung injury score and lung tissue W / D of aged rats in the PDX treatment group weresignificantly reduced ( P<0. 01) . The protein concentration and the contents of IL-1β, IL-6 and TNF-α in alveolarlavage fluid were significantly decreased ( P<0. 01) , the MDA, ROS content and NF-κB protein expression in lungtissue were significantly reduced, SOD activity and HO-1 Protein expression was significantly increased ( P <0. 05) . Conclusion PDX could significantly reduce the lung injury after lobectomy in elderly rats. This effectmay be related to the regulation of HO-1 and NF-κB protein expression in the lung tissues, thereby inhibiting theoxidative stress and inflammation in the lungs.