摘要
目的:探讨椒目油A2(ZSOA2)对不同时相哮喘小鼠肺组织核因子-кB(NF-кB)信号通路和炎症细胞因子的影响。方法:采用腹腔注射20%Al(OH)3+10%卵蛋白(OVA)混合液致敏并每天1次呼吸道滴入50μL(0.4%OVA磷酸缓冲液pH=7.4)制备小鼠哮喘模型。在滴入后24 h、48 h、3 d、7 d、14 d分别处死小鼠,ELISA法测定肺灌洗液(BALF)中白细胞介素-4(IL-4)、白细胞介素-5(IL-5)、干扰素-γ(IFN-γ)含量;HE染色法检测肺组织病理形态学及伊红染色计数炎性细胞分类;Western blotting法测定肺组织NF-кB信号通路蛋白表达。结果:ZSOA2组能显著减少哮喘小鼠各时点肺组织嗜酸性粒细胞(EOS)、淋巴细胞(LY)(P<0.05);降低各时点BALF中IL-5、IL-4,升高IFN-γ的水平;下调肺组织中细胞黏附分子-1(ICAM-1)、血管内皮黏附分子-1(VCAM-1)、核因子抑制蛋白-α激酶(IKK-α)、磷酸化核因子抑制蛋白(p-IкB)的表达,上调肿瘤坏死因子受体1(TNF-R1)和磷酸化核因子-кB65(p-NF-кB65)蛋白表达水平。结论:ZSOA2治疗OVA诱发小鼠哮喘是下调肺组织内NF-кB信号通路中IKK-α和p-IкB表达,抑制细胞因子和趋化因子的释放与产生,使炎性细胞浸润程度减弱,而产生治疗哮喘的作用。
AIM： To investigate the dynamic influence of zanthoxylum seed oilA2 （ ZSOA2 ） on NF - κB signaling pathway and inflammatory factor in pulmonary tissue of asthmatic mice. METHODS： The suspensoid （0. 2 mL containing 20% albumin hydroxide and 10% ovalbumin） was administered by intraperitoneal injection to sensitize the BALB/c mice on day 1, then 0.4% ovalbumin solution （50 μL in phosphate buffer fluid） was dripped into the respiratory tract through nasal cavity to establish the asthmatic mouse model. After dripped ovalbumin for 24 h, 48 h, 3 d, 7 d and 14 d, the mice were killed at specified time points. The contents of interleukin- 4 （IL- 4）, interleukin -5 （IL- 5） and interferon -γ （IFN -γ） in bronchoalveolar lavage fluid （BALF） were determined by ELISA. The pathological changes of the lung tissues were observed with HE staining. The inflammatory cell counts were conducted by Eosin staining. The protein levels of adhesion molecule and the molecules of NF - κB signaling pathway in lung tissues were determined by Western blotting. RESULTS ： In ZSOA2 treated mice, the pathological injury of the lung was significantly attenuated as compared to the model mice, the counts of eosinophils and lymphocytes were reduced obviously in lung bronchial area of asthmatic mice at all observed time points （ P 〈 0. 05 ）. The levels of IL - 5 and IL - 4 decreased and IFN -γincreased in BALF. The resuits of Western blotting showed that ZSOA2 down - regulated the protein levels of intercellular adhesion molecule - 1, vascular cell adhesion molecule - 1, 1 kappa B kinase alpha - α and phosphorylation inhibitory - κB. ZSOA2 also up - regula ted the protein levels of tumor necrosis factor receptor 1 and phosphm＇ylation nuclear factor - kappaB in lung tissue at all observed time points. CONCLUSION： ZSOA2 has therapeutie effect on asthma by down - regulating the protein expression of IκB - β and p - 1κB, inhibiting the releases of cytokines and chemotactic factors, and attenuating the infiltration of inflammatory cells in the lungs of ovalbumin challenged asthma mice.
出处
《中国病理生理杂志》
CAS
CSCD
北大核心
2010年第6期1120-1126,共7页
Chinese Journal of Pathophysiology
基金
陕西省中医管理局科学基金资助项目(No.2005-076)
关键词
椒苜油
哮喘
NF-кB
白细胞介素-5
胞间黏附分子1
Zanthoxylum seed oil
Asthm,,
NF - kappa B
lnterlukin - 5
Intercellular adhesion molecule - 1
