摘要
目的研究人工麝香对卵白蛋白(OVA)致敏引发的小鼠气道炎症损伤的保护作用及其机制。方法雄性Balb/c小鼠分别于第0天和第14天腹腔注射20μg OVA和2.25 mg Al(OH)3凝胶致敏,于第28、29、30天从气管滴入OVA进行攻击,攻击前1 h给予受试化合物人工麝香及阳性药地塞米松。小鼠随机分为6组:正常对照组(n=11)、模型组(OVA组,n=10)、地塞米松组(Dex组,n=10)、人工麝香给药10 d组(n=11)、人工麝香给药7 d组(n=13)、人工麝香给药5 d组(n=11)。人工麝香皮下给药100 mg/kg,分别自致敏第21、24、26天开始给药,给药周期为10、7、5 d。处死小鼠后,对小鼠的体重、脾脏和胸腺进行称重,计算脾脏、胸腺指数。检测支气管肺泡灌洗液(BALF)炎症细胞及炎症因子IL-4、IL-5及IL-17含量改变,HE染色分析小鼠肺部病理变化,免疫组化分析中性粒细胞生物标志物Ly6G/Gr-1的表达水平。结果与模型组相比,人工麝香100 mg/kg连续给药5、7 d可改善OVA致敏引发的小鼠气道炎症,明显降低小鼠BALF炎症细胞因子IL-4、IL-5、IL-17的含量(P<0.05)。细胞分类计数、肺组织病理分析及免疫组化结果表明,人工麝香能够抑制小鼠肺部气道中炎症细胞,特别是中性粒细胞的浸润,以及中性粒细胞标志物Ly6G/Gr-1的表达。结论人工麝香具有较强的减轻OVA致敏引发的小鼠气道炎症损伤的功能,提示人工麝香对于哮喘可能有一定的治疗作用。
Objective To investigate the effects of artifitial musk on attenuation of OVA-challenged murine airway in- flammation in vivo and its mechanism. Methods Male Balb/c mice were divided into 6 groups, including control （n= 11）, OVA model （n=10）, Dex （n=10）, artifitial musk 10 days （n=11）, artifitial musk 7 days （n=13）, and artifitial musk 5 days （n=11）. Mice were immunized intraperitoneally with 20 μg ovalbumin （OVA） and 4 mg Al（OH）3 suspended in 0.1 mL saline solution on Day 0 and Day 14, and then intratracheally challenged with 1% OVA suspended in saline solution on Days 28-30. Artifitial musk （100 mg/kg, s.c.） was given 1 hour before each OVA challenge for 5, 7 and 10 days since the sensitization for 21, 24, 26 days, respectively. After sacrificed, the body weights, spleen index and thymus in- dex were calculated. In addition, pathologic changes in the lung tissues, number of inflammatory cells in bronchoalveo- lar lavage fluid （BALF） and expression levels of IL-4, IL-5, IL-17 were observed. Moreover, the expression levels of Ly6G/Gr-1, a major biomarker of neutrophil, was detected by immunohistochemical examination. Results Compared with OVA model, the airway inflammation in mice improved after treatment with 100 mg/kg artifitial musk for 5 and 7 days in vivo. Moreover, the expression levels of major cytokines as IL-4, IL-5 and IL-17 in BALF were inhibited after treatment with musk （P 〈 0.05）. Pathological and cell count results showed that the inflammatory cell especially neu- trophile granulocyte infiltration in the airway section reduced after treatment with artifitial musk. Furthermore, immuno- histochemical examination results showed that the expression levels of Ly6G/Gr-1 were inhibited upon the treatment.Conclusion The results showed that artifitial musk pos- sesses inhibitory effects on airway inflammation induced with OVA in vivo and the therapeutic function on asthma in the future.
出处
《中国医药导报》
CAS
2014年第17期4-7,12,共5页
China Medical Herald
基金
教育部高等学校博士学科点专项科研基金(编号2010 1106120023)
