摘要
目的观察氯胺酮对哮喘模型大鼠气道高反应性及炎症的影响。方法 56只 BrownNorway 大鼠随机分成阴性对照组(A 组)、哮喘模型组(B 组)和不同浓度氯胺酮雾化吸入预处理组(C组、D 组和 E 组)及不同剂量氯胺酮腹腔用药预处理组(F 和 G 组)。采用卵蛋白(OVA)辅以百日咳杆菌菌苗和氢氧化铝为佐剂注射致敏大鼠。雾化吸入10 mg/ml OVA 激发。氯胺酮预处理组大鼠在激发前分别给予12.5 mg/ml、25 mg/ml 或50 mg/ml 浓度的氯胺酮雾化吸入或50μg/kg,100μg/kg剂量的氯胺酮腹腔注射。A 组采用磷酸盐缓冲液替代 OVA 进行雾化吸入。最后1次激发后24 h,测定气道反应性。并取肺组织作诱导性一氧化氮合酶(iNOS)的基囚和蛋白表达,一氧化氮(NO)生成量及病理组织学检测。结果 (1)B 组的呼气阻力(Re)增长百分率的剂量反应曲线向左上移位,而且PC100(Re 增长达100%幅度时所需乙酰胆碱的激发剂量),PC200及 PC400值显著低于 A 组(分别为14.65±1.19vs32.28±1.43,15.17±1.19vs38.91±1.39及16.28±1.18vs56.53±1.38)差异有统计学意义(P<0.01)。氯胺酮预处理组的 Re 剂量反应曲线向右下移位,而 PC100,PC200及PC400值均明显高于 B 组(P<0.05)。(2)B 组可见明显的气道炎症性病理改变。氯胺酮治疗组炎症细胞浸润及上皮细胞损伤程度明显减轻,肺间质水肿改善。(3)B 组 iNOS 基因表达与 A 组相比明显增强(1.00±0.07vs0.48±0.07,P<0.01)。与 B 组相比,iNOS 基因的表达在 C 组(0.65±0.07),D 组(0.58±0.09),E 组(0.56±1.00)及 F 组(0.66±0.06)均减低,差异有统计学意义(P<0.05)。(4)与 A 组相比,B 组 iNOS 蛋白表达(0.54±0.08)明显增强(P<0.05),而与 B 组相比,iNOS 蛋白表达量在 C 组(0.20±0.03),D 组(0.18±0.03)及 F 组(0.21±0.04)均减低,差异有统计学意义(P<0.05)。(5)B 组肺组织 NO 产量[(0.39±0.04)μmol/g 蛋白]显著高于 A 组(P<0.01)。肺组织 NO 产量在 C 组[(0.19±0.03)μmol/g 蛋白],D 组[(0.17±0.0
Objective To observe the effects of ketamine on bronchial hyperresponsiveness and airway inflammation in equal asthma. Methods 56 Brown-Norway rats were randomly assigned to seven groups： negative control group （Group A）, asthma model group （Group B） and inhalation groups with nebulized ketamine at different concentrations （ Group C, D, E ） and intraperitoneal injection groups with ketamine at different doses （ Group F, G ）. The rats were sensitized by injection of ovalbumin （ OVA ） together with aluminum hydroxide and Bordetella pertussis as adjuvants, then challenged by repeated intermittent （thrice weekly） exposure to aerosolized OVA for two weeks. Before challenge, the sensitized rats were exposed to an aerosol of phosphate buffered saline（PBS） or ketamine at the concentrations of 12. 5 mg/ml, 25 mg/ml and 50 mg/ml respectively in Groups B, C, D and E. The sensitized rats were intraperitoneally injected with ketamine at the doses of 50 μg/kg or 100 μg/kg respectively in Group F and G. The sensitized rats in Group A received phosphate buffered solution （PBS） by inhalation. The airway reactivity to acetylcholine （ACH） was assessed in vivo 24 hr after the last OVA challenge, then the lungs were removed for measurement of the mRNA and protein expression of iNOS and production of NO and lung sections for histopathologic examination. Results （ 1 ） In the OVA-sensitized and challenged rats, the doseresponse curve of the expiratory resistance （ Re ） shifted to the upper-left ± ward compared with that of PBS control rats. In addition, the provocation doses required to increase the Re by 100% , 200% and 400% for OVA-sensitized and challenged rats in Group B were significantly lower than those of the PBS control rats （14.65 ±1. 19 vs 32. 28±1.43,15.17±1.19 vs 38.91±1.39,and 16.28±1.18 vs 56.53±1.38, all P〈 0. 01 ）. The OVA-sensitized rats treated with ketamine before OVA challenge demonstrated a significant decrease in AHR by a rightward shift of the dose-resp
出处
《中华医学杂志》
CAS
CSCD
北大核心
2007年第19期1308-1313,共6页
National Medical Journal of China
