不同剂量甲泼尼龙对肺炎支原体肺炎模型小鼠肺组织TLR4/NF-κB通路的影响

doi:10.3969/j.issn.1007-3205.2021.11.002

摘要/Abstract

摘要： 目的探究不同剂量甲泼尼龙对肺炎支原体肺炎模型小鼠肺组织Toll样受体4（Toll-like receptor 4，TLR4）/核因子κB（nuclear factor κB ，NF-κB）通路的影响。
方法选取40只SD健康雄性小鼠，随机选取10只为正常小鼠组，其余30只建立肺炎支原体肺炎小鼠模型，建模成功后随机选取10只做模型组，其余20只分别为低剂量干预组、高剂量干预组，其中低剂量干预组小鼠以低剂量甲泼尼龙进行注射，高剂量干预组小鼠以高剂量甲泼尼龙进行注射。比较各组间TLR4、NF-κB表达，免疫组织化学法检测TLR4、NF-κB水平，酶联免疫法检测及肿瘤坏死因子α（tumor necrosis factor-α，TNF-α）、白细胞介素1β（interleukin-1β，IL-1β）水平，黄嘌呤氧化酶法检测超氧化物歧化酶（superoxide dismutase，SOD），硫代巴比妥酸法检测丙二醛（malondialdehyde,MDA）。
结果相比正常小鼠组，模型组、低剂量干预组与高剂量干预组TLR4、NF-κB表达均较高，低剂量干预组与高剂量干预组TLR4、NF-κB表达低于模型组，且高剂量干预组TLR4、NF-κB表达低于低剂量干预组（P＜0.05）；相比正常小鼠组，模型组、低剂量干预组与高剂量干预组TLR4、NF-κB水平均较高，低剂量干预组与高剂量干预组TLR4、NF-κB水平低于模型组，且高剂量干预组TLR4、NF-κB水平低于低剂量干预组（P＜0.05）；相比正常小鼠组，模型组、低剂量干预组与高剂量干预组TNF-α、IL-1β水平均较高，低剂量干预组与高剂量干预组TNF-α、IL-1β水平低于模型组，且高剂量干预组TNF-α、IL-1β水平低于低剂量干预组（P＜0.05）；相比正常小鼠组，模型组、低剂量干预组与高剂量干预组MDA水平较高、SOD水平均较低，与模型组相比，低剂量干预组与高剂量干预组MDA水平较低、SOD水平较高，且高剂量干预组MDA水平低于、SOD水平高于低剂量干预组（P＜0.05）。
结论在肺炎支原体肺炎模型小鼠中，应用甲泼尼龙能够显著改善出现的肺组织损伤，抑制TLR4/NF-κB通路表达，降低炎症反应程度，改善氧化应激，且高剂量效果较为显著。

关键词: 肺炎, 支原体, 甲泼尼龙, 丙二醛

Abstract: Objective To investigate the effects of different doses of methylprednisolone on Toll-like receptor 4(TLR4)/nuclear factor κB (NF-κB) pathway in lung tissue of mouse model with Mycoplasma pneumoniae pneumonia.
Methods Forty healthy male SD mice were selected, of which 10 were randomly selected as normal mice group, and the remaining 30 were used to establish mouse model of Mycoplasma pneumoniae pneumonia. After successful modeling, 10 were randomly selected as model group, and the remaining 20 were selected as low-dose intervention group and high-dose intervention group. Low-dose intervention group was injected with low-dose methylprednisolone, while high-dose intervention group was injected with high-dose methylprednisolone. The expression of TLR4 and NF-κB was compared among groups. The levels of TLR4 and NF-κB were detected by immunohistochemistry. The levels of tumor necrosis factor-α(TNF-α) and interleukin 1β(IL-1β) were detected by enzyme-linked immunoassay. Superoxide dismutase(SOD) was detected by xanthine oxidase method and malondialdehyde(MDA) was detected by thiobarbituric acid method.
Results Compared with normal mice group, the expression of TLR4 and NF-κB was higher in model group, low-dose intervention group and high-dose intervention group, the expression of TLR4 and NF-κB in low-dose intervention group and high-dose intervention group was lower than that in model group, and the expression of TLR4 and NF-κB in high-dose intervention group was lower than that in low-dose intervention group(P＜0.05). Compared with normal mice group, the expression of TLR4 and NF-κB in model group, low-dose intervention group and high-dose intervention group was higher.The levels of TLR4 and NF-κB were lower in the low-dose intervention group and the high-dose intervention group than in the model group, and the levels of TLR4 and NF-κB in the high-dose intervention group were lower than those in the low-dose intervention group(P＜0.05). Compared with the normal mice group, the levels of TNF-α and LI-1β in the model group. The low-dose intervention group and the high-dose intervention group was higher, and the levels of TNF-α and LI-1β in the low-dose intervention group and the high-dose intervention group were lower than those in the model group. The level of TNF-α and IL-1β in the high-dose intervention group was lower than that in the low-dose intervention group(P＜0.05). Compared with the normal mice group, the MDA level was higher and SOD level was lower in the model group, the low-dose intervention group and the high-dose intervention group. The MDA level was lower and SOD level was higher in the low-dose intervention group and the high-dose intervention group, as compared with the model group, and the MDA level was lower and SOD was higher in the high-dose intervention group than in the low-dose intervention group(P＜0.05).
Conclusion In mouse model of Mycoplasma pneumoniae pneumonia, methylprednisolone can significantly improve the lung tissue damage, inhibit the expression of TLR4/NF-κB pathway, reduce the degree of inflammatory response, and improve oxidative stress, and the high-dose effect is more significant.

Key words: pneumonia, mycoplasma, methylprednisolone, malondialdehyde

张俊光, 张书丽, 张会英, 苏艳文. 不同剂量甲泼尼龙对肺炎支原体肺炎模型小鼠肺组织TLR4/NF-κB通路的影响[J]. 河北医科大学学报, 2021, 42(11): 1245-1250.

ZHANG Jun-guang, ZHANG Shu-li, ZHANG Hui-ying, SU Yan-wen. Effects of different doses of methylprednisolone on TLR4/NF-κB pathway in lung tissue of mouse model with Mycoplasma pneumoniae pneumonia[J]. Journal of Hebei Medical University, 2021, 42(11): 1245-1250.

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不同剂量甲泼尼龙对肺炎支原体肺炎模型小鼠肺组织TLR4/NF-κB通路的影响

Effects of different doses of methylprednisolone on TLR4/NF-κB pathway in lung tissue of mouse model with Mycoplasma pneumoniae pneumonia

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