目的 探讨1,8-桉油精(1,8-cineol)对哮喘豚鼠肺功能的改善作用及其机制.方法 豚鼠第0天和第7天ip给予0.5 ml含卵白蛋白(OVA)20 μg的氢氧化铝凝胶致敏,28 d后OVA攻击制备哮喘模型.观察豚鼠OVA攻击后1 h,1,8-桉油精10,30和100 mg·kg~(-1)对豚鼠吸入OVA后1,2,3,4,10,20和30 min时气道阻力(R_(aw))和肺顺应性(C_(dyn))变化及支气管肺泡灌洗液(BALF)中白细胞数和细胞分类的影响,并测量豚鼠肺组织中嗜酸细胞阳离子蛋白(ECP)、白细胞介素4(IL-4)、IL-8和肿瘤坏死因子α(TNF-α)的含量.观察豚鼠OVA攻击后17 h再吸入乙酰甲胆碱(MCh)后,1,8-桉油精10, 30和100 mg·kg~(-1)对R_(aw)和C_(dyn)及BALF中白细胞数和细胞分类的影响,并测量豚鼠肺组织中ECP, IL-4, IL-8和TNF-α的含量.结果 与正常对照组比较,豚鼠OVA攻击后1 h,在4 min时模型组R_(aw)达到高峰;与模型组比较,1,8-桉油精30和100 mg·kg~(-1)明显抑制R_(aw)增加(P<0.05);在3 min时模型组C_(dyn)达到高峰,与模型组比较,1,8-桉油精10, 30和100 mg·kg~(-1)均能明显抑制C_(dyn)降低(P<0.05);模型组豚鼠肺组织ECP, IL-4和TNF-α含量明显高于正常对照组(P<0.05);1,8-桉油精100 mg·kg~(-1)组ECP, IL-4和TNF-α含量均明显低于模型组(P<0.05),模型组与正常对照组豚鼠肺组织IL-8含量无明显差异.与模型组比较,1,8-桉油精100 mg·kg~(-1)能明显减少BALF中白细胞数和嗜酸性粒细胞比例(P<0.05).致敏豚鼠OVA攻击17 h后, 模型组豚鼠R_(aw)与正常对照组比较显著升高(P<0.05),模型组豚鼠C_(dyn)与正常对照组比较有显著性差异(P<0.01),1,8-桉油精100 mg·kg~(-1)对MCh 引起的R_(aw)的增加有明显的抑制作用,1,8-桉油精10, 30和100 mg·kg~(-1)对MCh引起的C_(dyn)降低有明显的改善作用;与模型组相比,1,8-桉油精100 mg·kg~(-1)能明显减少BALF中白细胞数和中性粒细胞比例,降低肺组织ECP, IL-8和TNF-α含量(P<0.01);模型组与正常对照组豚鼠肺组织IL-4含量无明显差异;1,8-桉油精30 mg·kg~(-1)也能降低哮喘豚鼠肺组织中ECP和TNF-α含量(P<0.01).结论 在哮喘急性发作时,1,8-桉油精通过减少嗜酸性粒细胞,下调嗜酸性粒细胞的活性,从而抑制了哮喘的急性发作.在哮喘迟发相阶段,1,8-桉油精可通过下调IL-8水平,降低TNF-α活性,从而抑制或改善由IL-8水平升高导致的中性粒细胞聚集于支气管肺泡而直接引起的哮喘加重和持续状态.
目的 探討1,8-桉油精(1,8-cineol)對哮喘豚鼠肺功能的改善作用及其機製.方法 豚鼠第0天和第7天ip給予0.5 ml含卵白蛋白(OVA)20 μg的氫氧化鋁凝膠緻敏,28 d後OVA攻擊製備哮喘模型.觀察豚鼠OVA攻擊後1 h,1,8-桉油精10,30和100 mg·kg~(-1)對豚鼠吸入OVA後1,2,3,4,10,20和30 min時氣道阻力(R_(aw))和肺順應性(C_(dyn))變化及支氣管肺泡灌洗液(BALF)中白細胞數和細胞分類的影響,併測量豚鼠肺組織中嗜痠細胞暘離子蛋白(ECP)、白細胞介素4(IL-4)、IL-8和腫瘤壞死因子α(TNF-α)的含量.觀察豚鼠OVA攻擊後17 h再吸入乙酰甲膽堿(MCh)後,1,8-桉油精10, 30和100 mg·kg~(-1)對R_(aw)和C_(dyn)及BALF中白細胞數和細胞分類的影響,併測量豚鼠肺組織中ECP, IL-4, IL-8和TNF-α的含量.結果 與正常對照組比較,豚鼠OVA攻擊後1 h,在4 min時模型組R_(aw)達到高峰;與模型組比較,1,8-桉油精30和100 mg·kg~(-1)明顯抑製R_(aw)增加(P<0.05);在3 min時模型組C_(dyn)達到高峰,與模型組比較,1,8-桉油精10, 30和100 mg·kg~(-1)均能明顯抑製C_(dyn)降低(P<0.05);模型組豚鼠肺組織ECP, IL-4和TNF-α含量明顯高于正常對照組(P<0.05);1,8-桉油精100 mg·kg~(-1)組ECP, IL-4和TNF-α含量均明顯低于模型組(P<0.05),模型組與正常對照組豚鼠肺組織IL-8含量無明顯差異.與模型組比較,1,8-桉油精100 mg·kg~(-1)能明顯減少BALF中白細胞數和嗜痠性粒細胞比例(P<0.05).緻敏豚鼠OVA攻擊17 h後, 模型組豚鼠R_(aw)與正常對照組比較顯著升高(P<0.05),模型組豚鼠C_(dyn)與正常對照組比較有顯著性差異(P<0.01),1,8-桉油精100 mg·kg~(-1)對MCh 引起的R_(aw)的增加有明顯的抑製作用,1,8-桉油精10, 30和100 mg·kg~(-1)對MCh引起的C_(dyn)降低有明顯的改善作用;與模型組相比,1,8-桉油精100 mg·kg~(-1)能明顯減少BALF中白細胞數和中性粒細胞比例,降低肺組織ECP, IL-8和TNF-α含量(P<0.01);模型組與正常對照組豚鼠肺組織IL-4含量無明顯差異;1,8-桉油精30 mg·kg~(-1)也能降低哮喘豚鼠肺組織中ECP和TNF-α含量(P<0.01).結論 在哮喘急性髮作時,1,8-桉油精通過減少嗜痠性粒細胞,下調嗜痠性粒細胞的活性,從而抑製瞭哮喘的急性髮作.在哮喘遲髮相階段,1,8-桉油精可通過下調IL-8水平,降低TNF-α活性,從而抑製或改善由IL-8水平升高導緻的中性粒細胞聚集于支氣管肺泡而直接引起的哮喘加重和持續狀態.
목적 탐토1,8-안유정(1,8-cineol)대효천돈서폐공능적개선작용급기궤제.방법 돈서제0천화제7천ip급여0.5 ml함란백단백(OVA)20 μg적경양화려응효치민,28 d후OVA공격제비효천모형.관찰돈서OVA공격후1 h,1,8-안유정10,30화100 mg·kg~(-1)대돈서흡입OVA후1,2,3,4,10,20화30 min시기도조력(R_(aw))화폐순응성(C_(dyn))변화급지기관폐포관세액(BALF)중백세포수화세포분류적영향,병측량돈서폐조직중기산세포양리자단백(ECP)、백세포개소4(IL-4)、IL-8화종류배사인자α(TNF-α)적함량.관찰돈서OVA공격후17 h재흡입을선갑담감(MCh)후,1,8-안유정10, 30화100 mg·kg~(-1)대R_(aw)화C_(dyn)급BALF중백세포수화세포분류적영향,병측량돈서폐조직중ECP, IL-4, IL-8화TNF-α적함량.결과 여정상대조조비교,돈서OVA공격후1 h,재4 min시모형조R_(aw)체도고봉;여모형조비교,1,8-안유정30화100 mg·kg~(-1)명현억제R_(aw)증가(P<0.05);재3 min시모형조C_(dyn)체도고봉,여모형조비교,1,8-안유정10, 30화100 mg·kg~(-1)균능명현억제C_(dyn)강저(P<0.05);모형조돈서폐조직ECP, IL-4화TNF-α함량명현고우정상대조조(P<0.05);1,8-안유정100 mg·kg~(-1)조ECP, IL-4화TNF-α함량균명현저우모형조(P<0.05),모형조여정상대조조돈서폐조직IL-8함량무명현차이.여모형조비교,1,8-안유정100 mg·kg~(-1)능명현감소BALF중백세포수화기산성립세포비례(P<0.05).치민돈서OVA공격17 h후, 모형조돈서R_(aw)여정상대조조비교현저승고(P<0.05),모형조돈서C_(dyn)여정상대조조비교유현저성차이(P<0.01),1,8-안유정100 mg·kg~(-1)대MCh 인기적R_(aw)적증가유명현적억제작용,1,8-안유정10, 30화100 mg·kg~(-1)대MCh인기적C_(dyn)강저유명현적개선작용;여모형조상비,1,8-안유정100 mg·kg~(-1)능명현감소BALF중백세포수화중성립세포비례,강저폐조직ECP, IL-8화TNF-α함량(P<0.01);모형조여정상대조조돈서폐조직IL-4함량무명현차이;1,8-안유정30 mg·kg~(-1)야능강저효천돈서폐조직중ECP화TNF-α함량(P<0.01).결론 재효천급성발작시,1,8-안유정통과감소기산성립세포,하조기산성립세포적활성,종이억제료효천적급성발작.재효천지발상계단,1,8-안유정가통과하조IL-8수평,강저TNF-α활성,종이억제혹개선유IL-8수평승고도치적중성립세포취집우지기관폐포이직접인기적효천가중화지속상태.
OBJECTIVE To investigate the effects of 1,8-cineol on lung functions and mechanism in asthmatic guinea pigs. METHODS The guinea pig model was performed by intraperitoneal injection of the 0.5 ml Al(OH)_3 gel containing OVA 20 μg. The guinea pigs were constructed by immunization of intraperitoneal injection on the 0 day and the 7th day, and the experiment was performed on the 28th day. The effect of 1,8-cineol 10, 30 and 100 ml·kg~(-1) on the airway resistance(R_(aw)) and dynamic lung compliance (C_(dyn)) of asthmatic guinea pigs 1 h after challenge of OVA. The changes in leukocyte and different kinds of leukocyte in bronchoalveolar lavage fluid (BALF) after the challenge of OVA have been studied. The levels of eosinophil cationic protein (ECP), interleukin(IL)-4, IL-8 and tumor necrosis factor (TNF)-α in lungs of guinea pigs were determined using enzyme-linked immunosorbent assay (ELISA). The changes in R_(aw) and C_(dyn) of asthmatic guinea pigs were investigated 17 h after challenge of OVA and inhalated methacholine (MCh). The changes in leukocyte and different kinds of leukocyte in BALF after the challenge of OVA have been studied. The levels of ECP, IL-4, IL-8 and TNF-α in lungs of guinea pigs were determined using ELISA. RESULTS 1,8-Cineol inhibited increase in R_(aw) and decrease in C_(dyn) from 1 to 30 min after challenge of OVA in model group. The levels of ECP, IL-4 and TNF-α in asthmatic model group were higher than those in normal control group(P<0.05). The levels of ECP, IL-4 and TNF-α of 1,8-cineol 100 mg·kg~(-1) group were significantly lower than those in asthmatic model group (P<0.01). The level of IL-8 of asthmatic model group didn't have any significant difference from that of control group. 1,8-Cineol 100 mg·kg~(-1) could significantly decrease the numbers of leukocyte and the percent of eosinophils in BALF. Seventeen hours after challenge of OVA, R_(aw) and C_(dyn) of asthmatic model group were higher than these of control group (P<0.05, P<0.01); 1,8-cineol 100 mg·kg~(-1) significantly inhibited the increase in R_(aw), compared with model group (P<0.05); 1,8-cineol 10, 30 and 100 mg·kg~(-1) improved the decrease in C_(dyn) after MCh-induced in model group which were challenged by OVA after 17 h; 1,8-cineol 100 mg·kg~(-1) could significantly decrease the numbers of leukocyte and the percent of neutrophils, the levels of ECP, IL-8 and TNF-α compared with asthmatic group. The level of IL-4 in asthmatic model group didn't have any significant difference from that in normal control group. CONCLUSION In the course of early stage of asthma, 1,8-cineol inhibites the asthma by decreasing the number of eosinophils and down-regulating the activity of EPO. In the course of later stage of asthma, 1,8-cineol inhibits or improves the aggravation and lasting states of asthma which is directly coursed by neutrophils accumulating in the BALF that related to the increase in IL-8.
