在小鼠哮喘模型中牛乌头碱A可有效缓解过敏性肺部炎症
2019/05/10
摘要
背景：牛乌头碱A (BLA)在我国已广泛应用于慢性炎症性疼痛的镇痛。然而，其对哮喘的潜在治疗作用仍不清楚。本研究旨在探讨BLA对过敏性哮喘小鼠气道炎症的影响。
材料和方法：SPF级雌性Balb/c小鼠随机分为6组:(1)对照组(NC)，(2)哮喘组(AS)， (3) BLA-L组，(4)BLA-M组，(5)BLA-H组，(6)地塞米松组。采用卵清蛋白(OVA)给药建立哮喘小鼠模型，在最后一次给药后24小时内处死小鼠。采用酶联免疫吸附法(ELISA)测定小鼠血清中IgE和IgG的相对表达水平。此外,收集支气管肺泡灌洗液(BALF)和用ELISA测定IL- 4, TNF-α,MCP-1表达水平。对BALF中的嗜酸性细胞、淋巴细胞和巨噬细胞进行分类分析，苏木精-伊红染色(HE)检测小鼠气道炎症细胞浸润情况。NF-κB1和PKC-δ小鼠肺组织的表达是由免疫印迹分析。
结果：与哮喘(AS)组小鼠相比，BLA或地塞米松组小鼠的血清球蛋白和免疫球蛋白水平显著降低 (P < 0.01),而细胞因子IL- 4,TNF-α和MCP-1表达水平明显降低(P < 0.01)。HE染色显示BLA明显减少肺组织炎症细胞浸润和粘液分泌。此外,BLA通过肺组织的NF-κB信号通路抑制NF-κB1和PKC-d的表达。
结论：我们的数据表明,BLA通过激活PKC-δ/ NF-κB减轻过敏性哮喘小鼠气道炎症。
Bulleyaconitine A Effectively Relieves Allergic Lung Inflammation in a Murine Asthmatic Model.
Zhan X, Zhang W, Sun T, Feng Y, Xi Y, Jiang Y, Tang X.
Abstract
BACKGROUND ：Bulleyaconitine A (BLA) has been widely used as analgesic against chronic inflammatory pain in China. However, its potential therapeutic role in asthma remains unclear. The purpose of this study was to investigate the effect of BLA on airway inflammation in mice with allergic asthma.
MATERIAL AND METHODS ：Specific-pathogen-free (SPF) female Balb/c mice were randomly divided into the following 6 groups: (1) Control group (NC), (2) Asthma group (AS), (3) BLA-L group, (4) BLA-M group, (5) BLA-H group, and (6) Dexamethasone group. An asthma mouse model was established by administration of ovalbumin (OVA) and mice were sacrificed within 24 h after the last challenge. Enzyme-linked immunosorbent assay (ELISA) method was used to determine the relative expression levels of IgE and IgG in mouse serum. In addition, bronchoalveolar lavage fluid (BALF) was collected and IL-4, TNF-α, and MCP-1 levels were determined by ELISA. Furthermore, eosinophils, lymphocytes, and macrophages in BALF were classified and analyzed, and inflammatory cell infiltration in the airways of mice was determined by hematoxylin-eosin (HE) staining. The expression of NF-κB1 and PKC-δ in mouse lung tissue was determined by Western blot analysis.
RESULTS ：The levels of serum IgE and IgG in BLA- or Dex- treated mice were significantly reduced compared to those in the asthma (AS) group (P<0.01), whereas the levels of cytokines IL-4, TNF-α, and MCP-1 were significantly decreased (P<0.01). HE-staining showed that BLA significantly reduced inflammatory cell infiltration and mucus secretion in lung tissue. Moreover, BLA inhibited the expression of NF-κB1 and PKC-d via the NF-κB signaling pathway in the lung.
CONCLUSIONS：Our data show that BLA activates PKC-δ/NF-κB to reduce airway inflammation in allergic asthma mice.
背景：牛乌头碱A (BLA)在我国已广泛应用于慢性炎症性疼痛的镇痛。然而，其对哮喘的潜在治疗作用仍不清楚。本研究旨在探讨BLA对过敏性哮喘小鼠气道炎症的影响。
材料和方法：SPF级雌性Balb/c小鼠随机分为6组:(1)对照组(NC)，(2)哮喘组(AS)， (3) BLA-L组，(4)BLA-M组，(5)BLA-H组，(6)地塞米松组。采用卵清蛋白(OVA)给药建立哮喘小鼠模型，在最后一次给药后24小时内处死小鼠。采用酶联免疫吸附法(ELISA)测定小鼠血清中IgE和IgG的相对表达水平。此外,收集支气管肺泡灌洗液(BALF)和用ELISA测定IL- 4, TNF-α,MCP-1表达水平。对BALF中的嗜酸性细胞、淋巴细胞和巨噬细胞进行分类分析，苏木精-伊红染色(HE)检测小鼠气道炎症细胞浸润情况。NF-κB1和PKC-δ小鼠肺组织的表达是由免疫印迹分析。
结果：与哮喘(AS)组小鼠相比，BLA或地塞米松组小鼠的血清球蛋白和免疫球蛋白水平显著降低 (P < 0.01),而细胞因子IL- 4,TNF-α和MCP-1表达水平明显降低(P < 0.01)。HE染色显示BLA明显减少肺组织炎症细胞浸润和粘液分泌。此外,BLA通过肺组织的NF-κB信号通路抑制NF-κB1和PKC-d的表达。
结论：我们的数据表明,BLA通过激活PKC-δ/ NF-κB减轻过敏性哮喘小鼠气道炎症。
(中日友好医院呼吸与危重症医学科 禹汶伯 摘译 林江涛 审校)
(Med Sci Monit. 2019 Mar 4;25:1656-1662. doi: 10.12659/MSM.915427.)
(Med Sci Monit. 2019 Mar 4;25:1656-1662. doi: 10.12659/MSM.915427.)
Bulleyaconitine A Effectively Relieves Allergic Lung Inflammation in a Murine Asthmatic Model.
Zhan X, Zhang W, Sun T, Feng Y, Xi Y, Jiang Y, Tang X.
Abstract
BACKGROUND ：Bulleyaconitine A (BLA) has been widely used as analgesic against chronic inflammatory pain in China. However, its potential therapeutic role in asthma remains unclear. The purpose of this study was to investigate the effect of BLA on airway inflammation in mice with allergic asthma.
MATERIAL AND METHODS ：Specific-pathogen-free (SPF) female Balb/c mice were randomly divided into the following 6 groups: (1) Control group (NC), (2) Asthma group (AS), (3) BLA-L group, (4) BLA-M group, (5) BLA-H group, and (6) Dexamethasone group. An asthma mouse model was established by administration of ovalbumin (OVA) and mice were sacrificed within 24 h after the last challenge. Enzyme-linked immunosorbent assay (ELISA) method was used to determine the relative expression levels of IgE and IgG in mouse serum. In addition, bronchoalveolar lavage fluid (BALF) was collected and IL-4, TNF-α, and MCP-1 levels were determined by ELISA. Furthermore, eosinophils, lymphocytes, and macrophages in BALF were classified and analyzed, and inflammatory cell infiltration in the airways of mice was determined by hematoxylin-eosin (HE) staining. The expression of NF-κB1 and PKC-δ in mouse lung tissue was determined by Western blot analysis.
RESULTS ：The levels of serum IgE and IgG in BLA- or Dex- treated mice were significantly reduced compared to those in the asthma (AS) group (P<0.01), whereas the levels of cytokines IL-4, TNF-α, and MCP-1 were significantly decreased (P<0.01). HE-staining showed that BLA significantly reduced inflammatory cell infiltration and mucus secretion in lung tissue. Moreover, BLA inhibited the expression of NF-κB1 and PKC-d via the NF-κB signaling pathway in the lung.
CONCLUSIONS：Our data show that BLA activates PKC-δ/NF-κB to reduce airway inflammation in allergic asthma mice.
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丙酸氟替卡松、孟鲁司特钠、酮替芬治疗小儿咳嗽变异性哮喘的临床疗效观察
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