阿托伐他汀钙对脂多糖诱导急性肺损伤小鼠核因子 E2相关因子 2/血红素加氧酶 -1通路的影响

李姗; 王荣丽

文章摘要

李姗,王荣丽.阿托伐他汀钙对脂多糖诱导急性肺损伤小鼠核因子 E2相关因子 2/血红素加氧酶 -1通路的影响[J].安徽医药,2023,27(8):1521-1525.

阿托伐他汀钙对脂多糖诱导急性肺损伤小鼠核因子 E2相关因子 2/血红素加氧酶 -1通路的影响

Effect of atorvastatin calcium on Nrf2/HO-1 pathway in mice with lipopolysaccharide-induced acute lung injury

DOI：10.3969/j.issn.1009-6469.2023.08.009

中文关键词: 阿托伐他汀钙急性肺损伤核因子 E2相关因子 2 血红素加氧酶 -1 肿瘤坏死因子 -α 白细胞介素 -1β

英文关键词: Atorvastatin calcium Acute lung injury Nuclear factor-E2 related factor 2 Heme oxygenase-1 Tumor necrosis factor-α Interleukin-1β

基金项目:

作者	单位	E-mail
李姗	西南医科大学附属医院呼吸与危重症医学科，四川泸州 646000
王荣丽	西南医科大学附属医院呼吸与危重症医学科，四川泸州 646000	scybwrl@sina.com

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中文摘要:

目的探讨阿托伐他汀钙( AVT)对脂多糖( LPS)诱导急性肺损伤( ALI)小鼠核因子 E2相关因子 2/血红素加氧酶 -1(Nrf2/HO-1)通路的影响。方法 2021年 9―12月，采用随机数字表法把 15只 BALB/c雌性小鼠分为 NS组(尾静脉注射生理盐水)、 LPS组(尾静脉注射 LPS诱导 ALI模型)、 LPS+AVT组(经 AVT灌胃治疗的 ALI模型)每组各 5只。收集动脉血，测定血氧分压( PaO₂)、氧合指数( PaO₂/FiO₂)；处死后取出双肺， HE染色观察肺组织，测定湿干重比(，W/D)，酶联免疫吸附( ELISA)法测肺泡灌洗液( BALF)中白细胞介素 -1β(IL-1β)、肿瘤坏死因子 -α(TNF-α)含量，蛋白质印迹法( Western blotting)测肺组织中 Nrf2、HO-1的表达。结果 NS组、 LPS组及 LPS+AVT组 PaO₂［( 89.66±8.54)、(50.88±6.26)、(67.84±5.76)mmHg］、 PaO₂/FiO₂［( 426.95±40.67)、(242.29±29.79)、(323.05±27.42)mmHg］、 W/D(3.12±0.54、4.95±0.60、3.85±0.46)、 IL-1β［( 37.95±6.18)、(115.09±12.42)、(75.61±7.89)ng/L］、 TNF-α［( 63.66±20.71)、(330.99±41.71)、(220.87±28.89)ng/L］、 Nrf2(0.43±0.03、0.08±0.02、0.22±0.03)及 HO-1(0.59±0.07、0.09±0.03、0.22±0.03)。与 NS组相比， LPS组肺泡结构混乱不清，肺泡壁增厚，腔内炎性细胞大量渗出堆积， PaO₂及 PaO₂/FiO₂降低， W/D比值增加， BALF IL-1β、TNF-α含量增多，肺组织 Nrf2、HO-1蛋白表达相对降低(均 P<0.05)。与LPS组相比， LPS+AVT组肺泡结构清晰度高，肺泡壁厚度及腔内炎性渗出改善， PaO₂及 PaO₂/FiO₂升高， W/D比值降低， BALF IL-1β、TNF-α含量减少，肺组织 Nrf2、HO-1蛋白含量增多(均 P<0.05)。结论 AVT可减轻 LPS诱导 ALI小鼠的炎症反应，这可能与激活 Nrf2/HO-1通路有关。

英文摘要:

Objective To investigate the effect of atorvastatin calcium (AVT) on nuclear factor E2-related factor 2/ heme oxygenase1(Nrf2/HO-1) pathway in mice with lipopolysaccharide (LPS) -induced acute lung injury (ALI).Methods From September to December 2021, fifteen female BALB/c mice were assigned randomly into NS group (injection with normal saline), LPS group (ALI model inducted by intra-tail injection with LPS) and LPS+AVT group (ALI model treated by intragastric administration with AVT), with 5 mice in each group. The arterial blood was taken for detecting the partial pressure of oxygen (PaO₂) and the oxygenation index (PaO₂/FiO₂).The lung tissues were observed by HE staining and detected for wet/dry ratio (W/D). Enzyme linked immunosorbent assay (ELISA) was used to measure the expression of Interleukin-1β (IL-1β), Tumor necrosis factor-α (TNF-α) in bronchoalveolar lavage fluid (BALF) and western blot was used to proteins of Nrf2 and HO-1 in lung tissues.Results PaO₂ in NS group, LPS group and LPS+AVT group was respectively [(89.66±8.54), (50.88±6.26), (67.84±5.76) mmHg]; PaO₂/FiO₂ was [(426.95±40.67), (242.29±29.79), (323.05±27.42) mmHg];W/D was (3.12±0.54, 4.95±0.60, 3.85±0.46); IL-1β was [(37.95±6.18), (115.09±12.42), (75.61±7.89) ng/L]; TNF-α was [(63.66±20.71),(330.99±41.71), (220.87±28.89) ng/L]; Nrf2 was (0.43±0.03, 0.08±0.02, 0.22±0.03) and HO-1 was (0.59±0.07, 0.09±0.03, 0.22 ±0.03).Compared with NS group, alveolar structure in LPS group was distorted, alveolar septa was thickened, alveolar spaces were accumulated with inflammatory cells; the levels of PaO₂, PaO₂/FiO₂, and proteins of Nrf2 and HO-1 in pulmonary tissue were decresed (P<0.05), while W/D ratio, IL-1β and TNF-α in BALF were increased (P<0.05). Compared with the LPS group, structure distortion, alveolar septa thickening and inflammatory cells accumulation in LPS+AVT group were reduced; the levels of PaO₂, PaO₂/FiO₂, and proteins of Nrf2 and HO-1 in lung tissues were increased (P<0.05), while W/D ratio, IL-1β and TNF-α in BALF were decreased (P<0.05).Conclusion AVT can reduce the inflammatory response in LPS-induced ALI mice, which may be related to the activation of Nrf2/HO-1 pathway.

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