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| Rho/Rock 信号通路在大鼠呼吸机相关性肺损伤中的作用 |
| Role of Rho/Rock signaling pathways in ventilator-induced lung injury in rats |
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| DOI：10.12089/jca.2016.12.017 |
| 中文关键词: Rho/Rock信号通路 呼吸机相关性肺损伤 机械通气 |
| 英文关键词: Rho/Rock signaling Ventilator-induced lung injury Mechanical ventilation |
| 基金项目:江西省卫生计生委科技计划项目(20141881) |
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| 中文摘要: |
| 目的：评价 Rho/Rock 信号通路在大鼠呼吸机相关性肺损伤(ventilator-induced lung injury,VILI)中的作用。方法选择健康雄性 SD 大鼠96只,12~15周龄,体重300~350 g,采用随机数字表法将大鼠随机分为四组：空白对照组(C 组)、Rho 激酶抑制药法舒地尔组(F 组)、高潮气量组(H 组)和高潮气量+Rho 激酶抑制药法舒地尔组(HF 组),每组24只。C 组和 F 组不行机械通气,H 组和 HF 组行高潮气量40 ml/kg 机械通气4 h。F 组和 HF 组在机械通气前1 h 给予腹腔注射法舒地尔10 mg/kg。分别于通气前(T0)、通气后4 h(T1)、8 h(T2)和24 h(T3)每组随机取6只大鼠,采集血样,测定血清 TNF-α、IL-6及 IL-10浓度；采血结束后处死大鼠,收集支气管肺泡灌洗液(BALF),采用考马斯亮兰法检测 BALF 总蛋白；测定肺组织湿/干重比(W/D)；光镜下行肺组织病理学损伤评分；采用分光光度法检测肺组织髓过氧化物酶(MPO)活性；采用 Western blot 和 RT-PCR法分别检测肺组织 RhoA、Rock2蛋白含量和 mRNA 表达水平。结果与 C 组比较,T1~T3时 H组和 HF 组大鼠血清 TNF-α、IL-6及 IL-10浓度、BALF 总蛋白含量、肺组织 W/D、病理学损伤评分、MPO 活性、RhoA、Rock2蛋白含量和 mRNA 表达水平明显升高(P <0.05)；与 H 组比较,T1~T3时 HF 组大鼠血清 TNF-α、IL-6浓度、BALF 总蛋白含量、肺组织 W/D、病理学损伤评分、MPO 活性、RhoA、Rock2蛋白含量和 mRNA 表达水平明显下降,血清 IL-10浓度明显升高(P <0.05)。结论 Rho激酶抑制药法舒地尔可减轻大鼠呼吸机相关性肺损伤,其机制可能与其抑制 Rho/Rock 信号通路,降低肺组织内炎性反应有关。 |
| 英文摘要: |
| Objective To investigate the role of Rho/Rock signaling pathways in ventilator-in-duced lung injury in rats.Methods Ninety-six male SD rats,weighing 300-350 g,were equally and randomly divided into four groups using a random number table (n =24 each):control group (group C),fasudil group (group F),high tidal volume group (group H)and high tidal volume + fasudil group (group HF).Rats in group C and group F received no mechanical ventilation,rats in group H and group HF were intubated and mechanically ventilated (VT = 40 ml/kg,RR = 40 beats per minutes,FiO 2 =40%)for 4 h.The animals in group F and group HF were given intraperitoneal in-jection of fasudil 10 mg/kg at the time 1 h before mechanically ventilated.Six rats were chosen in each group at the time before ventilation (T0 )and at 4,8,24 h after ventilation (T1-T3 ),and blood sam-ples were taken for determination of the levels of serum tumor necrosis factor-α (TNF-α),IL-6 and IL-10,lungs were removed,bronchoalveolar lavage fluid (BALF)was collected to examine protein content,wet/drying (W/D)ratio was determined,which were then stained with haematoxylin and e-osin and examined under microscope,the pathological changes of lungs were scored.Myeloperoxidase (MPO)activity in lung tissue was determined by spectrophptometry.Protein and gene expression of RhoA and Rock2 in the lung tissue were detected by Western blot and reverse transcription PCR (RT-PCR).Results Compared with group C,the serum TNF-α,IL-6 and IL-10,BALF protein content, W/D ratio,the pathological scores,MPO activity,the expression of RhoA,Rock2 protein and mR-NA were significantly increased in group H and HF at T1-T3 (P <0.05 ).Compared with group H, the serum TNF-αand IL-6,BALF protein content,W/D ratio,the pathological scores,MPO activi-ty,the expression of RhoA,Rock2 protein and mRNA were significantly decreased,and the serum IL-10 was significantly increased in group HF at T1-T3 (P <0.05).Conclusion Fasudil can attenuate ventilator-induced lung injury in rats,and the mechanism may be associated with inhibition of the Rho/Rock signaling pathways reducing the inflammatory response. |
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