摘要
目的探讨内源性硫化氢(H2S)靶向单核细胞趋化调控百草枯(PQ)诱导的急性肺损伤的效果。方法健康清洁级SD雄性大鼠90只,随机数字表法分为对照大鼠(NS组)、PQ染毒大鼠(PQ组)、PQ染毒+H2S激动剂(PQ+CSE组)、PQ染毒+单核细胞趋化蛋白-1抑制剂(PQ+Bindarit组)、PQ染毒+H2S抑制剂(PQ+PPG组)、PQ染毒+H2S抑制剂+单核细胞趋化蛋白-1抑制剂(PQ+PPG+Bindarit组)6组,各15只。PQ灌胃12 h后(干预药物预处理2 h)即处理各组大鼠,比较各组肺组织大体与HE染色情况,并比较各组肺湿干重比、肺损伤评分、血清H2S、BALF中的细胞计数与肺组织单核细胞、血清和肺泡灌洗液(BALF)中和单核细胞系统炎症指标[单核细胞趋化蛋白-1(MCP-1)、肿瘤坏死因子-α(TNF-α)、白介素-1(IL-1)、可溶性肿瘤坏死因子受体(sTNFR)及白介素1受体(IL-1ra)]水平。结果与正常大鼠(NS组)相比,PQ染毒后肺湿干重比、肺损伤评分、BALF细胞总数、肺组织单核细胞评分、BALF单核细胞、BALF中MCP-1、TNF-α、IL-1增加,血清H2S降低(P<0.05);给予H2S激动剂CSE后,肺湿干重比、肺损伤评分、BALF细胞总数、肺组织单核细胞评分、BALF单核细胞、BALF中MCP-1、TNF-α、IL-1[(3.85±0.14)分、(5.77±0.71)分、(2.22±0.49)×108/L、(2.47±0.19)分、(0.17±0.08)×105/L、(551.24±139.78)pg/mL、(214.77±20.83)pg/mL、(110.07±16.25)pg/mL]降低,而给予H2S抑制剂PPG后,肺湿干重比、肺损伤评分、BALF细胞总数、肺组织单核细胞评分、BALF单核细胞、BALF中MCP-1、TNF-α、IL-1[(5.98±0.17)分、(14.51±1.89)分、(6.48±1.07)×108/L、(5.04±0.25)分、(0.36±0.11)×105/L、(948.76±240.16)pg/mL、(422.16±36.09)pg/mL、(196.69±15.42)pg/mL]显著增加,差异有统计学意义(F=915.960、265.647、106.152、1625.025、36.389、46.689、360.268、184.075,P<0.05);给予MCP-1抑制剂Bindarit后,肺湿干重比、肺损伤评分、BALF细胞总数、肺组织单核细胞评分、BALF单核细胞、BALF中MCP-1、TNF-α、IL-1较PQ染毒大鼠明显降低,差异有统计学意义(P<0.05)。结论内源性H2S可靶向单核细胞在肺组织的趋化和增殖,调控肺部炎症反应,从而参与PQ诱导的急性肺损伤,MCP-1抑制剂或CSE有望成为抗PQ急性肺损伤治疗的新靶点。
Objective To investigate the effect of endogenous hydrogen sulfide(H2S)targeting monocyte chemotaxis in regulating paraquat(PQ)-induced acute lung injury.Methods 90 healthy and clean SD male rats were randomly divided into control rats(NS group),PQ-exposed rats(PQ group),PQ-exposed+H2S agonist(PQ+CSE group),PQ Exposure+monocyte chemoattractant protein-1 inhibitor(PQ+Bindarit group),PQ exposure+H2S inhibitor(PQ+PPG group),PQ exposure+H2S inhibitor+monocyte chemoattractant protein-1 Inhibitors(PQ+PPG+Bindarit group)6 groups,each with 15 rats.After PQ gavage for 12 h(intervention drug pretreatment 2 h),the rats in each group were treated,and the general lung tissue of each group was compared with the HE staining condition,and the lung wet-to-dry weight ratio,lung injury score,serum H2S,BALF were compared.The cell count and lung tissue monocytes,serum and alveolar lavage fluid(BALF)neutralize the inflammation indicators of the monocyte system[monocyte chemoattractant protein-1(MCP-1),tumor necrosis factor-α(TNF-α),interleukin-1(IL-1),soluble tumor necrosis factor receptor(sTNFR)and interleukin 1 receptor(IL-1ra)]levels.Results Compared with normal rats(NS group),the wet-to-dry lung weight ratio,lung injury score,total number of BALF cells,lung mononuclear cell score,BALF monocytes,MCP-1 and TNF-α,in BALF after PQ exposure.IL-1 increased and serum H2S decreased(P<0.05);after administration of H2S agonist CSE,lung wet-to-dry weight ratio,lung injury score,total number of BALF cells,lung tissue monocyte score,BALF monocytes,BALF Medium MCP-1,TNF-α,IL-1[(3.85±0.14)points,(5.77±0.71)points,(2.22±0.49)×108/L,(2.47±0.19)points,(0.17±0.08)×105/L,(551.24±139.78)pg/mL,(214.77±20.83)pg/mL,(110.07±16.25)pg/mL]decreased,and after administration of H2S inhibitor PPG,lung wet-to-dry weight ratio,lung injury score,total number of BALF cells,lung mononuclear cell score,BALF monocytes,MCP-1,TNF-α,IL-1 in BALF[(5.98±0.17)points,(14.51±1.89)points,(6.48±1.07)×108/L,(5.04±0.25)points,(0.36±0.11)×105/L,(948.76±240.16)pg/mL,(422.16±36.09)pg/mL,(196.69±15.42)pg/mL]significantly increased,the difference was statistical significance(F=915.960,265.647,106.152,1625.025,36.389,46.689,360.268,184.075,P<0.05);after administration of MCP-1 inhibitor Bindarit,lung wet-to-dry weight ratio,lung injury score,total number of BALF cells,lung tissue mononuclear cell score,BALF monocytes,and MCP-1,TNF-α,and IL-1 in BALF were significantly lower than those in PQ-exposed rats,the difference was statistical significance(P<0.05).Conclusion Endogenous H2S can target the chemotaxis and proliferation of monocytes in lung tissue,regulate lung inflammation,and participate in PQ-induced acute lung injury.MCP-1 inhibitors or CSE are expected to be new target for anti-PQ acute lung injury treatments.
作者
周克兵
曾国琼
王旻
何玉淑
贺海亮
刘成
邓立普
谷刚
ZHOU Ke-bing;ZENG Guo-qiong;WANG Min;HE Yu-shu;HE Hai-liang;LIU Cheng;DENG Li-pu;GU Gang(General Practice,Nanhua Hospital,Nanhua University,Hengyang,Hunan Province,412000 China)
出处
《系统医学》
2020年第22期17-21,共5页
Systems Medicine
基金
湖南省科技厅课题:内源性H2S通过调控肺泡炎症反应单核细胞趋化拮抗百草枯诱导急性肺损伤(2017SK50220)。
