消退素D1对百草枯致急性肺损伤大鼠肺泡表面活性物质与巨噬细胞的影响

目的  探讨消退素D1对于百草枯诱导的急性肺损伤大鼠体内肺泡表面活性物质水平和肺泡巨噬细胞功能的影响。方法  将90只健康雄性SD大鼠完全随机分为3组：对照组（C组：生理盐水2.5 ml/kg、生理盐水2.5 ml/kg）、百草枯组（P组：百草枯60 mg/kg、生理盐水2.5 ml/kg）、消退素D1组（Rv组：百草枯60 mg/kg、消退素5μg/kg）。按照分组情况，每组分别给予规定量的生理盐水或百草枯灌胃造模，3 h后再给予规定量的生理盐水或消退素D1尾静脉注射。百草枯给药24 h后取大鼠肺脏组织，采用实时荧光定量PCR法检测其中肺泡表面活性蛋白A、B及C-mRNA的表达水平，采用BCA法测定肺泡灌洗液中总蛋白含量。采用体外培养的大鼠肺泡巨噬细胞研究消退素D1对其功能的影响。结果  3组大鼠肺泡表面3种活性蛋白mRNA的表达差异有统计学意义，其中对照组大鼠肺泡表面活性蛋白的表达量最高，消退素D1组其次，百草枯组最低（P < 0.05）。3组大鼠肺泡灌洗液中总蛋白含量差异均有统计学意义，其中消退素D1组大鼠灌洗液中总蛋白的含量最高，百草枯组其次，对照组最低（P <0.05）。加入百草枯的体外培养肺泡巨噬细胞的培养上清液中白细胞介素-6（IL-6）、肿瘤坏死因子-α（TNF-α）和乳酸脱氢酶（LDH）含量增加（P <0.05），同时，消退素D1可以降低由于百草枯导致的IL-6、TNF-α和LDH含量的增加（P <0.05）。结论  消退素D1可通过促进肺泡表面活性蛋白表达、抑制巨噬细胞分泌IL-6、TNF-α和LDH等炎症因子来达到治疗由百草枯导致的急性肺损伤的目的。

Effect of resolvin D1 on surfactant and alveolar macrophages in rats with Paraquat-induced acute pulmonary injury

Objective To investigate the effect of resolvin D1 on pulmonary surfactant and alveolar macrophages (AM) in rats with pulmonary injury which was induced by Paraquat. Methods Ninety rats with pulmonary injury were randomly divided into 3 groups: control group (group C, normal saline, normal saline), Paraquat group (group P, Paraquat, normal saline) and resolvin D1 group (group Rv, Paraquat, resolvin D1). According to the grouping information, normal saline or Paraquat was given for modeling, and 3 hours later resolvin D1 or normal saline was given for treatment. The rat lung tissues were collected 24 hours after mo-deling to detect the mRNA expression levels of of surfactant proteins A, B and C using RT-PCR. The total protein in the bronchial alveolar lavage fluid (BALF) was also detected. The effect of resolvin D1 on AM was measured on isolated rat AM. Results The expression of three surfactant protein mRNAs in the three groups was different, where the expression level was the highest in the group C, the second in the group Rv, and the lowest in the group P (P < 0.05). The total protein content in BALF was also different, where it was the highest in the group C, the second in the group Rv, and the lowest in the group P (P < 0.05). The content of IL-6, TNF-α and LDH increased when Paraquat was added to in vitro culture medium (P < 0.05); while adding resolvin D1 reversed it (P < 0.05). Conclusions Resolvin D1 can help to treat pulmonary injury induced by Paraquat through boosting the expression of surfactant proteins and inhibiting the release of IL-6, TNF-α and LDH.