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为了探讨右美托咪定通过抑制炎症和自噬作用抵抗脂多糖诱导的小鼠急性肺损伤及其对MAPK通路的影响。本研究选取SPF级雄性C57/BL6J雄性小鼠36只,随机均分为3组:正常组(B组)、模型组(L组)和右美托咪定处理组(D组)。取小鼠右肺下叶,称量并计算湿/干比重(W/D);石蜡切片后染色,显微镜下分析肺组织病理学改变;ELISA试剂盒检测相关炎症因子:肿瘤坏死因子(tumor necrosis factor-α, TNF-α)、白介素-6 (interleukin-6, IL-6)、炎症促进因子(inflammation promoting factor, TH-1)水平;实时荧光定量PCR定量分析肺组织中TNF-α、IL-6和TH-1基因mRNA水平;Western blotting方法检测肺组织中TNF-α、IL-6与TH-1蛋白的含量;从而更进一步分析肺组织MAPK信号通路中基因的表达情况。实验结果表明,采用右美托咪定治疗的给药组小鼠肺损伤评分情况明显优于L组和B组小鼠,差异有统计学意义(p<0.05);给药组肺组织湿干比(W/D)(5.19±0.38)明显小于脂多糖肺损伤组(6.37±0.45)(p<0.05);给药组病理学评分(3.65±0.23)明显高于脂多糖肺损伤组(1.31±0.44)和对照组(3.14±0.44)。与正常对照组相比,给药组小鼠的肺组织水肿程度明显减轻,肺组织病理学改变减轻;RT-PCR结果也表明L组肺组织中TNF-α、IL-6与TH-1的mRNA表达量显著升高,而右美托咪啶处理后的表达量明显减少。另外,L组蛋白含量较B组、D组有明显减少,D组蛋白含量有所缓解。本研究结论初步表明:右美托咪啶能够抑制MAPK信号通路的激活。右美托咪定通过抑制炎症和自噬作用显著地减轻脂多糖导致的小鼠急性肺损伤,其机制可能是右美托咪定抑制MAPK通路的激活从而减轻炎症并调节自噬,从而实现保护肺脏的作用。
Abstract：To investigate the effect of dexmedetomidine on acute lung injury induced by lipopolysaccharide and its effect on MAPK pathway by inhibiting inflammation and autophagy. Thirty-six male C57/BL6J male mice of SPF grade were randomly divided into three groups: Normal group(group B), model group(group L) and dexmedetomidine treatment group(group D). The right lower lobe of the mouse was taken, the wet/dry specific gravity(W/D)was weighed and sampled; The paraffin section was stained, and the pathological changes of the lung tissue were analyzed under the microscope; The ELISA kit was used to detect the related inflammatory factor: Tumor necrosis factor(tumor necrosis) Factor-α, TNF-α, interleukin-6(IL-6), and inflammation promoting factor(TH-1) levels;Quantitative analysis of TNF-α and IL-6 in lung tissue by Real-time fluorescent quantitative PCR The mRNA levels of IL-6 and TH-1 genes were detected by Western blotting. The expressions of TNF-α, IL-6 and TH-1 in lung tissue were further analyzed. The expression of genes in MAPK signaling pathway in lung tissue was further analyzed. The results of the experiment showed that the lung injury scores of the mice treated with dexmedetomidine were significantly better than those of the L group and the B group(p<0.05). The lung tissue of the drugadministered group was wet and dry. The ratio(W/D)(5.19±0.38) was significantly less than that of the lipopolysaccharide-induced lung injury group(6.37±0.45)(p<0.05). The pathological score of the drug-administered group(3.65±0.23) was significantly higher than that of the lipopolysaccharide-induced lung injury group(1.31±0.44) and the control group(3.14±0.44). Compared with the normal control group, the lung tissue edema degree of the mice in the drug-administered group was significantly reduced, and the pathological changes of the lung tissue were alleviated; RT-PCR results also showed that TNF-α, IL-6 and TH-1 in the lung tissue of the L group were observed.The mRNA expression level was significantly increased, while the expression level after dexmedetomidine treatment was significantly reduced. In addition, the protein content of group L was significantly lower than that of group B and group D, and the protein content of group D was relieved. The results show that dexmedetomidine can inhibit the activation of the MAPK signaling pathway. Dexmedetomidine significantly attenuates lipopolysacch-arideinduced acute lung injury in mice by inhibiting inflammation and autophagy, possibly by dexmedetomidine inhibiting MAPK pathway activation, thereby reducing inflammation and regulating autophagy, thereby achieving protection The role of the lungs.
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基本信息:
DOI：10.13417/j.gab.039.001937
中图分类号:R965
引用信息:
[1]潘雪琳,刘庆,张英,等.右美托咪啶通过抑制炎症和自噬逆转脂多糖诱导的急性肺损伤[J].基因组学与应用生物学,2020,39(04):1937-1944.DOI:10.13417/j.gab.039.001937.
2020-04-25
2020-04-25