苍术素调节CXCL12/CXCR4信号通路对哮喘幼年大鼠肺组织损伤的影响

doi:10.3969/j.issn.1006-5725.2024.19.002

摘要/Abstract

摘要：

目的探讨苍术素调节CXC趋化因子配体12（CXCL12）/趋化因子受体4（CXCR4）信号通路对哮喘幼年大鼠肺组织损伤的影响。方法 60只大鼠随机取12只SD幼年大鼠作为对照组（CON组），其余48只大鼠使用卵清蛋白（OVA）构建哮喘模型。将造模成功的哮喘大鼠随机平分为Model组、苍术素组（50 mg/kg苍术素）、CXCL-12组（5?μg/kg重组CXCL-12蛋白）以及苍术素 + CXCL-12组（50 mg/kg苍术素 + 5?μg/kg重组CXCL-12蛋白），每组均12只，连续给药14 d，CON组和Model组给予等量生理盐水。收集支气管肺泡灌洗液（BALF）检测中性粒细胞、嗜酸粒细胞百分比。ELISA法检测血清和BALF液中细胞因子水平；HE染色检测肺组织病理变化；Western blot检测CXCL12/CXCR4通路相关蛋白水平。结果与CON组相比，Model组大鼠肺组织病理评分、中性粒细胞百分比、嗜酸粒细胞百分比、IL-17、IL-4、IL-5、IL-13、IgE、OVA sIgE水平以及CXCL12、CXCR4蛋白水平均显著增加（P < 0.05）；与Model组相比，苍术素组大鼠肺组织病理评分、中性粒细胞百分比、嗜酸粒细胞百分比、IL-17、IL-4、IL-5、IL-13、IgE、OVA sIgE以及CXCL12、CXCR4蛋白水平均显著降低（P < 0.05），而CXCL-12组结果与苍术素组趋势相反；CXCL-12消除了苍术素对哮喘大鼠的改善效果。结论苍术素可能通过下调CXCL12/CXCR4信号通路对哮喘大鼠肺组织损伤起到改善作用。

关键词: 苍术素, CXCL12/CXCR4信号通路, 哮喘, 肺损伤

Abstract:

Objective To investigate the impact of Atractylodin on lung tissue damage in young asthmatic rats by regulating the CXC chemokine ligand 12 （CXCL12）/CXC chemokine receptor 4 （CXCR4） signaling pathway. Methods Twelve young SD rats were randomly selected from 60 rats as the control group （CON group）， while the remaining 48 rats were used to construct asthma models using ovalbumin （OVA）. Successfully modeled asthma rats were randomly separated into Model group， Atractylodin group （50 mg/kg Atractylodin）， and CXCL-12 group （5 μg/kg recombinant CXCL-12 protein） and Atractylodin+CXCL-12 group （50 mg/kg Atractylodin+5 μg/kg recombinant CXCL-12 protein）， with 12 in each group， continuously administered for 14 days. The CON and Model groups were given equal amounts of physiological saline. The percentages of neutrophils and eosinophils in bronchoalveolar lavage fluid （BALF） were detected. ELISA method was applied to detect cytokine levels in serum and BALF fluid； HE staining was applied to detect pathological changes in lung tissue； Western blot was applied to detect the levels of CXCL12/CXCR4 pathway related proteins. Results Compared with the CON group， the pathological score of lung tissue， percentage of neutrophils， percentage of eosinophils， the levels of IL-17， IL-4， IL-5， IL-13， IgE， OVA sIgE， and the protein levels of CXCL12 and CXCR4 in Model group were obviously increased （P < 0.05）； compared with the Model group， the pathological score of lung tissue， percentage of neutrophils， percentage of eosinophils， the levels of IL-17， IL-4， IL-5， IL-13， IgE， OVA sIgE， and the protein levels of CXCL12 and CXCR4 in the Atractylodin group were obviously reduced （P < 0.05）， the results in the CXCL-12 group were opposite to those in the Atractylodes group； CXCL-12 eliminated the improvement effect of atractylodes on asthma rats. Conclusion Atractylodin may improve lung tissue damage in asthmatic rats by down-regulating the CXCL12/CXCR4 signaling pathway.

Key words: Atractylodin, CXCL12/CXCR4 signaling pathway, asthma, lung damage

中图分类号:

R285.5

陈洋洋,马鸿琦,杨静,吴宗跃,朱萍. 苍术素调节CXCL12/CXCR4信号通路对哮喘幼年大鼠肺组织损伤的影响[J]. 实用医学杂志, 2024, 40(19): 2672-2677.

Yangyang CHEN,Hongqi MA,Jing YANG,Zongyue WU,Ping. ZHU. Impact of Atractylodin on lung tissue damage in young asthma rats by regulating the CXCL12/CXCR4 signaling pathway[J]. The Journal of Practical Medicine, 2024, 40(19): 2672-2677.

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组别	嗜酸粒细胞	中性粒细胞
CON组	4.79 ± 0.58	10.47 ± 0.93
Model组	30.87 ± 0.46^*	24.48 ± 3.94^*
苍术素组	10.62 ± 1.15^△	12.36 ± 1.93^△
CXCL-12组	52.54 ± 4.74^△	33.36 ± 3.17^△
苍术素+CXCL-12组	27.67 ± 3.34^▲	28.31 ± 3.13^▲
F值	298.959	75.204
P值	< 0.001	< 0.001

组别	IL-13	IL-4	IL-5	IL-17
CON组	11.79 ± 2.58	16.53 ± 1.69	26.43 ± 1.76	36.90 ± 4.23
Model组	54.87 ± 6.46^*	48.58 ± 5.24^*	65.32 ± 5.88^*	68.56 ± 8.78^*
苍术素组	22.12 ± 3.35^△	24.35 ± 2.59^△	31.54 ± 2.76^△	43.09 ± 6.98^△
CXCL-12组	84.54 ± 9.34^△	65.85 ± 7.37^△	97.64 ± 8.12^△	96.54 ± 15.43^△
苍术素+CXCL-12组	43.67 ± 4.64^▲	43.36 ± 4.45^▲	52.46 ± 3.45^▲	56.23 ± 8.34^▲
F值	145.931	104.498	200.844	37.253
P值	< 0.001	< 0.001	< 0.001	< 0.001

组别	IL-13	IL-4	IL-5	IL-17
CON组	10.23 ± 2.70	15.69 ± 1.68	21.38 ± 3.27	41.79 ± 4.75
Model组	49.54 ± 6.50^*	43.93 ± 4.26^*	52.38 ± 6.37^*	64.87 ± 5.56^*
苍术素组	18.58 ± 3.35^△	22.47 ± 2.53^△	30.28 ± 3.87^△	42.12 ± 3.77^△
CXCL-12组	69.29 ± 9.37^△	61.49 ± 8.63^△	85.53 ± 9.39^△	84.12 ± 7.34^△
苍术素+CXCL-12组	41.58 ± 4.38^▲	39.38 ± 2.48^▲	48.56 ± 5.09^▲	63.67 ± 6.12^▲
F值	101.639	91.519	101.895	59.800
P值	< 0.001	< 0.001	< 0.001	< 0.001

组别	IgE	OVA sIgE
CON组	8.56 ± 0.83	0.00 ± 0.00
Model组	21.58 ± 1.37^*	19.63 ± 2.58^*
苍术素组	10.83 ± 0.83^△	5.48 ± 0.55^△
CXCL-12组	37.28 ± 4.63^△	35.83 ± 4.35^△
苍术素+CXCL-12组	18.72 ± 2.34^▲	12.36 ± 1.84^▲
F值	128.250	199.204
P值	< 0.001	< 0.001

组别	评分
CON组	0.06 ± 0.01
Model组	2.37 ± 0.29^*
苍术素组	0.74 ± 0.07^△
CXCL-12组	3.85 ± 0.42^△
苍术素+CXCL-12组	1.94 ± 0.25^▲
F值	198.884
P值	< 0.001