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1.遵义医科大学附属医院呼吸与危重症医学科二病区,遵义 563003
2.贵州省仁怀市贵州茅台医院呼吸内科,仁怀 564500
冉 燕,Email:ranyan365@163.com。 研究方向:急性肺损伤的发病机制,肺部感染的基础与临床研究。
赵建军,Email:610559131@qq.com。
收稿日期:2025-04-02,
修回日期:2025-07-18,
网络出版日期:2025-09-25,
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冉燕,王世艳,赵建军.β-谷甾醇对LPS致急性肺损伤大鼠肺泡巨噬细胞极化及NF-κB通路的影响[J].重庆医科大学学报,
Ran Yan,Wang Shiyan,Zhao Jianjun.Effects of β-sitosterol on alveolar macrophage polarization and NF-κB pathway in lipopolysaccharide-induced acute lung injury in rats[J].Journal of Chongqing Medical University,
冉燕,王世艳,赵建军.β-谷甾醇对LPS致急性肺损伤大鼠肺泡巨噬细胞极化及NF-κB通路的影响[J].重庆医科大学学报, DOI:10.13406/j.cnki.cyxb..
Ran Yan,Wang Shiyan,Zhao Jianjun.Effects of β-sitosterol on alveolar macrophage polarization and NF-κB pathway in lipopolysaccharide-induced acute lung injury in rats[J].Journal of Chongqing Medical University, DOI:10.13406/j.cnki.cyxb..
目的
2
观察β-谷甾醇(beta sitosterol,BS)是否可以影响脂多糖(lipopolysaccharide,LPS)诱导的大鼠急性肺损伤(acute lung injury,ALI),探讨其是否能影响核因子κB(nuclear factor kappa B,NF-κB)通路及肺泡巨噬细胞的极化。
方法
2
30只无特定病原体(specific pathogen free,SPF)SD大鼠随机分为生理盐水对照组(NS组)、急性肺损伤组(LPS组)、β-谷甾醇低剂量干预组(BS-L组)、β-谷甾醇高剂量干预组(BS-H组)和地塞米松组(DX组),每组6只,造模成功后处死大鼠,检测各组大鼠肺组织病理学变化及测量肺组织湿干重比值(weight/dry,W/D);支气管肺泡灌洗液肿瘤坏死因子α(tumor necrosis factor α,TNF-α)、白细胞介素1β(interleukin 1β,IL-1β)细胞因子水平;肺组织NF-κB p65、IL-1β、TNF-α mRNA相对表达情况;肺组织NF-κB p65、TNF-α蛋白表达水平以及肺组织中CD80标记的M1肺泡巨噬细胞(classically activated macrophages,M1)百分比。
结果
2
①与NS组比较,LPS组、BS-L组、BS-H组及DX组可观察到行为异常伴发绀,BS不同剂量干预组和DX组较LPS组减轻;②与NS组相比,LPS组肺组织病理损伤评分、W/D比值、肺组织NF-κB p65、IL-1β和TNF-α mRNA相对表达水平、肺组织TNF-α、NF-κB p65蛋白表达水平、M1肺泡巨噬细胞表面标志物CD80百分比、BALF中炎症因子TNF-α、IL-1β浓度水平均升高(均
P<
0.010);③与LPS组相比,BS-L组、BS-H组及DX组肺组织病理损伤评分、W/D比值、肺组织NF-κBp65、IL-1β和TNF-α mRNA相对表达水平、肺组织NF-κB p65、TNF-α蛋白表达水平、M1肺泡巨噬细胞表面标志物CD80百分比、BALF中炎症因子TNF-α、IL-1β水平降低(
P
均
<
0.001);④BS-H组低于BS-L组(均
P
<
0.001);与BS-L组和BS-H组比较,DX组大鼠上述指标降低(均
P
<
0.010)
结论
2
BS可能能抑制NF-κB通路的激活,抑制ALI大鼠肺泡巨噬细胞向M1型巨噬细胞极化,减轻ALI程度。
Objective
2
To investigate whether beta-sitosterol(BS) can affect the polarization of alveolar macrophages and the nuclear factor kappa B(NF-κB) pathway in a rat model of acute lung injury(ALI) induced by lipopolysaccharides(LPS).
Methods
2
Thirty specific pathogen-free Sprague-Dawley rats were randomly divided into normal saline group(NS group),ALI model group(LPS group),low-dose BS intervention group(BS-L group),high-dose BS intervention group(BS-H group),and dexamethasone group(DX group),with six rats in each group. After successful modeling,the rats were sacrificed for the following examinations:the pathological changes and wet-to-dry(W/D) weight ratio of lung tissue;the levels of tumor necrosis factor α(TNF-α) and interleukin 1β(IL-1β) in bronchoalveolar lavage fluid(BALF);the relative mRNA expression levels of NF-κB p65,IL-1β,and TNF-α in lung tissue; the protein expression levels of NF-κB p65 and TNF-α and the percentage of CD80-positive M1 alveolar macrophages in lung tissue.
Results
2
Abnormal behaviors and cyanosis were observed in all the groups except the NS group,with milder symptoms in the BS groups and DX group than in the LPS group. Compared with the NS group,the LPS group showed significant increases in the lung tissue pathological injury score,the W/D ratio,the relative mRNA expression levels of NF-κB p65,IL-1β,and TNF-α in lung tissue,the protein expression levels of TNF-α and NF-κB p65 in lung tissue,the percentage of CD80-positive M1 alveolar macrophages,and the levels of the inflammatory factors TNF-α and IL-1β in BALF(all
P
<
0.01). Compared with the LPS group,the BS-L group,BS-H group and DX group showed significant decreases in the lung tissue pathological injury score,the W/D ratio,the relative expression levels of NF-κB p65,IL-1β,and TNF-α mRNAs in lung tissue,the protein expression levels of NF-κB p65 and TNF-α in lung tissue,the percentage of CD80-positive M1 alveolar macrophages,and the levels of TNF-α and IL-1β in BALF(all
P
<
0.001). The above indicators were significant
ly lower in the BS-H group than in the BS-L group(all
P
<
0.001). Compared with those in the BS-L and BS-H groups,the above indicators in the DX group were significantly decreased(all
P
<
0.01).
Conclusion
2
BS may alleviate the severity of ALI through inhibiting the activation of the NF-κB pathway and suppressing the polarization of alveolar macrophages towards M1-type macrophages in ALI rats.
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