基于NOD样受体热蛋白结构域3/胱天蛋白酶-1通路探讨鱼腥草注射液缓解脂多糖诱导的小鼠急性肺炎肺损伤的作用机制  

The mechanism of houttuynia cordata injection in alleviating acute lipopolysaccharide-induced lung injury in mice based on NLRP3/caspase-1 pathway

作　　者：简宇[1] 范婷 代凌云[1] 赵春虎[1] JIAN Yu;FAN Ting;DAI Lingyun;ZHAO Chunhu(Emergency Department,Jingzhou Central Hospital,Jingzhou,Hubei 434000,China)

机构地区：[1]荆州市中心医院急诊科,湖北荆州434000

出　　处：《安徽医药》2023年第1期73-78,I0006,共7页Anhui Medical and Pharmaceutical Journal

摘　　要：目的探究鱼腥草注射液(HHI)对急性肺炎小鼠的保护作用及对NOD样受体热蛋白结构域3(NLRP3)/胱天蛋白酶-1(caspase-1)通路的调控作用。方法2019年7月至2020年6月,将购自广东省医学实验动物中心的90只BALB/c雄性小鼠分为正常对照组、模型组、HHI低(10 mL/kg)及高(30 mL/kg)剂量组、NLRP3激动剂(DDC)组(300 mg/kg)、HHI+DDC组(30 mL/kg+300 mg/kg),每组15只。除正常对照组外,其余各组均通过雾化吸入脂多糖(LPS)2.5 g/L建立急性肺炎模型。末次给药后检测支气管肺泡灌洗液(BALF)中白细胞介素-6(IL-6)、肿瘤坏死因子(TNF-α)水平、中性粒细胞数目;取右肺,检测右肺湿重/干重(W/D);左肺组织病理损伤情况,肺组织凋亡相关斑点样蛋白(ASC)mRNA及蛋白、NLRP3 mRNA及蛋白、TNF-α、IL-6、caspase-1蛋白表达水平。结果与正常对照组比较,模型组小鼠出现肺泡破坏及炎性细胞浸润等病理损伤现象,W/D、IL-6[(1692.06±95.26)µg/L比(569.91±50.89)µg/L]、TNF-α[(1846.24±99.26)µg/L比(506.99±55.48)µg/L]水平及中性粒细胞数目[(66.24±2.56)×10^(6)个/毫升比(5.09±1.98)×10^(6)个/毫升]、肺组织NLRP3 mRNA及蛋白(1.01±0.13比0.22±0.12)、ASC mRNA及蛋白(1.03±0.13比0.29±0.11)、caspase-1(1.06±0.14比0.25±0.12)、TNF-α、IL-6蛋白表达升高(P<0.05);与模型组相比,HHI低、高剂量组肺泡破坏及炎性细胞浸润等现象缓解,W/D、小鼠BALF中炎性因子IL-6[(1069.13±75.12)µg/L、(889.02±65.13)µg/L比(1692.06±95.26)µg/L]、TNF-α[(1225.33±84.02)µg/L、(806.63±69.12)µg/L比(1846.24±99.26)µg/L]含量及中性粒细胞数目[(45.33±2.22)×10^(6)个/毫升、(22.63±2.02)×10^(6)个/毫升比(66.24±2.56)×10^(6)个/毫升]、肺组织中NLRP3 mRNA及蛋白(0.83±0.11、0.52±0.12比1.01±0.13)、ASC mRNA及蛋白(0.82±0.12、0.54±0.11比1.03±0.13)、caspase-1(0.80±0.15、0.59±0.12比1.06±0.14)、TNF-α、IL-6蛋白表达降低(P<0.05);DDC组小鼠上述指标与HHI低、高剂量组相反(P<0.0Objective To investigate the protective effect of Herba Houttuyniae injection(HHI)on acute pneumonia in mice and the regulatory effect of HHI on the pathway of NOD-like receptor thermal protein domain 3(NLRP3)/caspase-1 pathway(caspase-1).Meth⁃ods From July 2019 to June 2020,male BALB/c mice purchased from Guangdong Medical Laboratory Animal Center were randomly assigned into normal control group,model group,HHI low(10mL/kg)and high(30 mL/kg)dose groups,NLRP3 agonist(diethyldithio‐carbamate,DDC)group(300 mg/kg),and HHI+DDC(30 mL/kg+300 mg/kg)group,with 15 mice in each group.Except for the control group,the other groups all established an acute pneumonia model by aerosol inhalation of LPS(2.5 g/L).The levels of interleukin-6(IL-6),tumor necrosis factor(TNF-α),and the number of neutrophils in the bronchoalveolar lavage fluid(BALF)were detected after the last administration.The right lung was taken and the wet/dry weight(W/D)of the right lung was detected.Left lung tissue pathological damage,lung tissue apoptosis-associated speck-like protein(ASC)mRNA and protein,NLRP3 mRNA and protein,TNF-α,IL-6,and caspase-1 protein expression levels were detected.Results Compared with the normal control group,mice in the model group showed pathological damage such as alveolar destruction and inflammatory cell infiltration,W/D,IL-6[(1692.06±95.26)µg/L vs.(569.91±50.89)µg/L],TNF-α[(1846.24±99.26)µg/L vs.(506.99±55.48)µg/L]levels and the number of neutrophils[(66.24±2.56)×10^(6)/mL vs.(5.09±1.98)×10^(6)/mL],lung tissue NLRP3 mRNA and protein[(1.01±0.13)vs.(0.22±0.12)],ASC mRNA and protein[(1.03±0.13)vs.(0.29±0.11)],caspase-1[(1.06±0.14)vs.(0.25±0.12)],TNF-α,and IL-6 protein expressions increased(P<0.05).Compared with the model group,alveolar destruction and inflammatory cell infiltration in the low-dose and high-dose HHI groups were relieved,W/D,the content of inflammatory factors IL-6[(1069.13±75.12)µg/L,(889.02±65.13)µg/L vs.(1692.06±95.26)µg/L],TNF-α[(1225.33±84.02)µg/L,(806.63±69.12)µg/L vs.(

关 键 词：鱼腥草属 肺炎 NOD样受体热蛋白结构域3 胱天蛋白酶1 白细胞介素6 肿瘤坏死因子α 小鼠 近交BALB C 

分 类 号：R285.5[医药卫生—中药学]