右美托咪定通过调节线粒体分裂和耗氧量减轻细支气管肺炎小鼠肺损伤的机制

目的 探讨右美托咪定通过调节线粒体分裂和耗氧量减轻细支气管肺炎小鼠肺损伤的机制.方法 50只无特定病原体级雄性白化小鼠为研究对象,将所有小鼠按照实验设置分为5组:对照组、阴性对照组、低剂量右美托咪定组、中剂量右美托咪定组和高剂量右美托咪定组,各10只.除对照组外,其余4组通过人工感染铜绿假单胞菌的方法构造小鼠细支气管肺...

Mechanism of dexmedetomidine attenuating lung injury in mice with bronchial pneumonia by regulating mitochondrial division and oxygen consumption

Objective To explore the mechanism by which dexmedetomidine reduces lung injury in mice with bronchiole pneumonia by regulating mitochondrial division and oxygen consumption.Methods Fifty male albino mice of specific pathogen-free grade were the research objects.All mice were divided into 5 groups according to the experimental settings:control group,negative control group,low-dose dexmedetomidine group,and medium-dose dexmedetomidine group,and the high-dose dexmedetomidine group,each with 10 rats.Except for the control group,the other 4 groups were artificially infected with Pseudomonas aeruginosa to construct a mouse bronchiopneumonia lung injury model.A total of 40 mice were used for follow-up experiments,with 8 mice in each group.The control group and the negative control group were injected with the same amount of 0.9%sodium chloride solution intravenously,and the low-dose,medium-dose and high-dose dexmedetomidine groups were injected intravenously with 0.1,0.3,and 0.5 mg/kg dexmedetomidine,respectively,for a total of 4 weeks of continuous intervention.The oxygenation index and wet/dry weight ratio of each group of lungs were determined.The expression levels of proteins and mRNAs related to mitochondrial division were determined by Western blotting analysis and real-time polymerase chain reaction.The levels of interleukin(IL)-6,IL-1βand tumor necrosis factorα(TNF-α)in the serum were determined by enzyme-linked immunosorbent assay.The pathological changes of lung tissue in mice with lung injury was observed by H&E staining,and TUNEL positive cells were determined by TUNEL method.The activities of caspase-3,caspase-8 and caspase-9 enzymes were determined colorimetrically.Results Compared with the control group,the lung wet/dry weight ratio,lung injury score and oxygenation index of the negative control group were significantly increased,and the differences were statistically significant(P<0.05).Compared with the negative control group,the lung wet/dry weight ratio,lung injury score and oxygenation index of the 3 dexmedetomidine groups were significantly decreased,and the differences were statistically significant(P<0.05).Compared with the control group,the concentration of malondialdehyde in the lung tissue of the negative control group was significantly increased,and the activities of MnSOD,Ca²⁺-ATPase and Na⁺-K⁺-ATPase were significantly decreased,and the differences were statistically significant(P<0.05);Compared with the negative control group,the concentration of malondialdehyde in lung tissue of the 3 dexmedetomidine groups were significantly decreased,and the activities of MnSOD,Ca²⁺-ATPase and Na⁺-K⁺-ATPase were significantly increased,and the differences were statistically significant(P<0.05).Compared with the control group,the concentration of TNF-α,IL-6,IL-1βand the proportion of TUNEL positive cells in the negative control group were increased significantly,and the differences were statistically significant(P<0.05);Compared with the negative control group,the concentration of TNF-α,IL-6,IL-1βand the proportion of TUNEL-positive cells in the 3 dexmedetomidine group were significantly decreased,and the differences were statistically significant(P<0.05).Compared with the control group,the expression of Fis1,Mfn1 and Mfn2 mRNA in the lung tissue of the negative control group were significantly decreased,and the expression of Drp1,OPA1 mRNA and the expression of apoptotic proteins caspase-3,caspase-8 and caspase-9 were significantly increased,and the differences were statistically significant significance(P<0.05);Compared with the negative control group,the expression of Fis1,Mfn1 and Mfn2 mRNA in lung tissues of 3 dexmedetomidine groups were increased significantly,and the expression of Drp1,OPA1 mRNA and the expression of apoptotic proteins caspase-3,caspase-8 and caspase-9 were significantly decreased,and the difference was statistically significant(P<0.05).Conclusion Dexmedetomidine attenuates mitochondrial fusion and fission by reducing the levels of pro-inflammatory mediators and oxidative stress in lung tissues to protect mice from bronchiopneumonia-induced lung injury.