核苷酸结合寡聚化结构域样受体蛋白3炎性小体在慢性阻塞性肺疾病大鼠肺组织中的作用

Role of nucleotide-binding oligomerization domain-like receptor protein 3 inflammasome in lung tissue of chronic obstructive pulmonary disease rats

目的探讨核苷酸结合寡聚化结构域样受体蛋白3(NLRP3)在慢性阻塞性肺疾病(COPD)发病中的作用。方法用脂多糖+香烟烟熏法建立大鼠COPD模型。将模型大鼠随机分为模型组和实验组,每组12只;另取12只正常大鼠作为对照组。对照组于第2~13和15~30天腹腔注射等量的0.9%NaCl;模型组于每次烟熏前腹腔注射等量的0.9%NaCl;实验组在每次烟熏前按10 mg·kg^-1的剂量腹腔注射1 mg·mL^-1 AC-YVAD-CMK。用强迫震荡式小动物肺功能检测仪测量肺总量、肺顺应性和呼吸阻力,用免疫组化法检测NLRP3的表达水平。结果实验组、对照组和模型组的顺应性分别为(0.62±0.13),(0.68±0.21)和(0.43±0.13)mL·cm^-1 H2O,呼吸阻力分别为(0.07±0.02),(0.05±0.02)和(0.14±0.01)cm·H2 O·s·mL^-1,肺总量分别为(10.07±1.30),(10.09±2.51)和(7.71±1.79)mL,细支气管平滑肌厚度分别为(14.66±0.95),(10.84±0.97)和(19.69±1.90)μm^2·μm^-1,NLRP3表达水平分别为(44.26±6.77)×103,(15.93±2.89)×10^3和(103.02±18.91)×10^3,实验组和对照组的上述指标与模型组比较,差异均有统计学意义(均P<0.05)。结论COPD大鼠肺组织内NLRP3表达水平增高,阻断NLRP3炎性小体通路可作为防治COPD的方法。

Objective To explore the role of nucleotide binding oligomerization domain-like receptor protein 3(NLRP3)in the pathogenesis of chronic obstructive pulmonary disease(COPD).Methods The model of COPD in rats was established by the lipopolysaccharide+cigarette smoking method.The model rats were randomly divided into model and experimental groups with 12 cases per group.In addition,12 normal rats were taken as the control group.Control group was injected intraperitoneally with the same amount of 0.9% NaCl from day 2 to day 13 and from day 15 to day 30.In the model group,the same amount of 0.9% NaCl was injected intraperitoneally before each fumigation.Experimental group was intraperitoneally injected with 1 mg·mL^-1 AC-YVAD-CMK at a dose of 10 mg·kg^-1 before each fumigation.The total lung volume,lung compliance and respiratory resistance were measured with forced concussion small animal lung function detector.The expression level of NLRP3 was detected with immunohistochemistry.Results The compliance of the experimental group,control group and model group were(0.62±0.13),(0.68±0.21)and(0.43±0.13)mL·cm^-1H2O,the respiratory resistances of those 3 groups were(0.07±0.02),(0.05±0.02)and(0.14±0.01)cm·H2 O·s·mL^-1,the total lung indexes of those 3 groups were(10.07±1.30),(10.09±2.51)and(7.71±1.79)mL,the bronchiolar smooth muscle thickness of those 3 groups were(14.66±0.95),(10.84±0.97)and(19.69±1.90)μm^2·μm^-1,the expression levels of NLRP3 of those 3 groups were(44.26±6.77)×103,(15.93±2.89)×10^3 and(103.02±18.91)×10^3.There were significant differences in the above-mentioned indexes between experimental and control groups and model group(all P<0.05).Conclusion The expression of NLRP3 is increased in the lung tissue of COPD rats.Blocking the inflammatory body pathway of NLRP3 can be used as a method for the prevention and treatment of COPD.