蛋白酪氨酸激2/信号转导子与激活子3信号通路在大鼠呼吸机相关性肺损伤中的作用机制研究

Role of Janus kinase signal transducers 2 and activator of transcription 3 signaling pathway in ventilator-induced lung injury in rats

目的探讨蛋白酪氨酸激2/信号转导子与激活子3(JAK2/STAT3)信号通路在大鼠呼吸机相关性肺损伤(VILI)中的作用机制。方法按照体重将模型大鼠随机分为2组:模型组、抑制剂组,每组10只;另取20只正常大鼠作为正常组和溶剂组。建立VILI大鼠模型。造模前1 h,抑制剂组大鼠尾静脉注射AG490(JAK2/STAT3信号通路抑制剂)溶液10 mg·kg-1,溶剂组注射等剂量的二甲基亚砜,正常组和模型组注射等剂量的0.9%NaCl。以酶联免疫吸附法测定大鼠肺组织的髓过氧化物酶(MPO)活性,蛋白质印迹法检测大鼠肺组织中JAK2和p-STAT3的表达水平(灰度值)。结果正常组、溶剂组、模型组和抑制剂组的MPO活性分别为(0.13±0.06),(0.10±0.08),(0.44±0.11)和(0.28±0.07)U·g-1;这4组的JAK2蛋白的相对表达量分别为0.99±0.05,0.98±0.04,4.47±0.12和2.75±0.21;这4组的p-STAT3蛋白的相对表达量分别为1.00±0.06,0.99±0.08,4.82±0.25和2.83±0.16。上述指标:模型组与正常组相比,差异均有统计学意义(均P<0.05);抑制剂组与模型组相比,差异均有统计学意义(均P<0.05);正常组和溶剂组相比,差异均无统计学意义(均P>0.05)。结论在LIVI大鼠中,抑制JAK2/STAT3信号通路活性可有效降低大鼠肺组织内的炎性反应。

Objective To observe the role of Janus kinase signal transducers 2/activator of transcription 3(JAK2/STAT3)signaling pathway in ventilator-induced lung injury(VILI)in rats. Methods Successful rats model were randomly divided into two groups according to weight:model group and inhibitor group;another 20 normal rats were taken as normal group and solvent group. The VILI rats were established. Inhibitor group rats were injected with AG490(JAK2/STAT3 signaling pathway inhibitor) solution(10 mg·kg-1) 1 h before surgery;solvent group rats were injected with dimethyl sulfoxide(10 mg·kg-1);model group and normal group rats were injected with 0.9%NaCl(10 mg·kg-1),respectively. Enzyme linked immunosorbent assay(ELISA) was used to detect the myeloperoxidase(MPO) activity in the lung tissue of each group of rats. Western blot was used to detect the grayscale value of JAK2 and p-STAT3 in the lung tissue of each group of rats.Results The MPO activities in normal group,solvent group,model group and inhibitor group were(0. 13 ± 0. 06),(0. 10 ± 0. 08),(0. 44 ± 0. 11) and(0. 28 ± 0. 07) U·g-1,respectively;the relative expression levels of JAK2 in the4 groups were 0. 99 ± 0. 05,0. 98 ± 0. 04,4. 47 ± 0. 12 and 2. 75 ± 0. 21,respectively;the relative expression levels of p-STAT3 in the 4 groups were 1. 00 ± 0. 06,0. 99 ± 0. 08,4. 82 ± 0. 25 and 2. 83 ± 0. 16,respectively. Compared between model group and normal group,the differences of the factors were significant(all P < 0. 05). Compared between inhibitor group and model group,the differences of the factors were significant(all P < 0. 05). Compared between normal group and solvent group,the differences of the factors were not significant(all P > 0. 05). Conclusion In rats with LIVI,inhibition of JAK2/STAT3 signaling pathway activity can effectively reduce the inflammatory response in rat lung tissue.