不同诱导剂致慢性阻塞性肺疾病模型小鼠氧化应激损伤的实验研究

目的：观察脂多糖和博来霉素两种诱导剂对小鼠不同时间点氧化/抗氧化状态的干预作用，为采用以上诱导剂建立气虚痰阻型（COPD）动物模型提供实验依据。方法：96只小鼠随机分为正常组、博来霉素组、脂多糖组，每组32只。博来霉素组、脂多糖组小鼠采用滴鼻一次诱导分别给予浓度为3.75μg·μL-1的博来霉素40μL，5μg·μL-1的脂多糖40μL建立慢性阻塞性肺疾病动物模型。各组小鼠于造模第1天、7天、14天、28天观察记录小鼠整体状态、活动情况，并在采集四肢皮肤颜色、舌底颜色、尾巴颜色等中医体征后处死动物，每个时间点处死8只，取出肺组织，检测肺组织匀浆液中谷胱甘肽（GSH）、丙二醛（MDA）、超氧化歧化酶（SOD）、总抗氧化能力（T-AOC）含量。结果：与正常组比较，博来霉素组小鼠双目略显呆滞，毛发干枯无光泽，被毛蓬松直立，耳廓及四爪颜色紫暗，精神倦怠，不喜活动，偶见出现咳嗽、气喘、气急等；在7天、14天、28天时肺组织GSH含量明显降低（〈0.05或〈0.01）；1天、7天、14天、28天时MDA、SOD、T-AOC含量明显降低（〈0.05或〈0.01）。与正常组比较，脂多糖组小鼠双目略显呆滞，被毛柔顺稍有光泽，耳廓及四爪颜色淡红，精神倦怠，部分小鼠有扎堆现象；1天、7天时肺组织GSH、SOD含量明显降低（〈0.05或〈0.01），1天、7天、14天时MDA、T-AOC含量明显降低（〈0.05或〈0.01）。结论：博莱霉素组小鼠肺组织在第7天开始出现明显氧化抗氧化的失衡，随后有所减缓，氧化失衡持续持续至造模结束。脂多糖组小鼠肺组织在第1天开始出现明显的氧化抗氧化的失衡，随着时间的推移，氧化/抗氧化失衡得到调整至正常。

Experimental Observation of Lung Oxidative Stress Injury in Mice Model of Chronic Obstructive Pulmonary Disease Induced by Different Inducers

This study was aimed to observe the intervention effect of oxidation/antioxidation at different time point among mice induced by lipopolysaccharide （LPS） and bleomycin. It provided experimental basis for the establishment of chronic obstructive pulmonary disease （COPD） animal model with qi-deficiency and phlegm-obstructing pattern with inducers mentioned above. A total of 96 mice were randomly divided into the normal control group, bleomycin group, and LPS group, with 32 mice in each group. In the bleomycin group and LPS group, 40 μL of nasal drops were given with bleomycin at the concentration of 3.75 μg/μL or LPS at the concentration of 5 μg/μL, respectively to establish the COPD animal model with qi-deficiency and phlegm-obstructing pattern. On the 1st day, 7th day, 14th day and 28th day after the model establishment, the general status and activities of mice were recorded. And traditional Chinese medicine （TCM） signs such as skin color of the four limbs, skin color under the tongue and color of the tail were also collected when the animal model was sacrificed. At each time point, 8 mice were sacrificed. The lung tissues were removed. And the contents of GSH, MDA, SOD and T-AOC were detected in the homogenate of lung tissues. The results showed that compared with the normal control group, mice in the bleomycin group had slightly dull eyes, dry hair without burnish, upright and fluffy hair, dark purple skin color of the auricle and four claws, tiredness, inactivity, occasional cough, asthma or rapid breathing. The GSH content of lung tissues on the 7th day, 14th day and 28th day was obviously reduced （P〉.05, or P〉.01）. The MDA, SOD and T-AOC contents on the 1st day, 7th day, 14th day and 28th day were obviously reduced （P〉.05, or P〉.01）. Compared with the normal control group, mice in the LPS group had slightly dull eyes, soft hair with slight burnish, pale red skin color of the auricle and four claws, tiredness; some mice preferred to gather. Contents of GSH and SOD in lung tissues on the 1st day and 7th day were obviously reduced （P〉.05, or P〉.01）. Contents of MDA and T-AOC on the 1st day, 7th day and 14th day were obviously reduced （P 〉.05, or P 〉.01）. It was concluded that obvious oxidation/antioxidation imbalance started on the 7th day in lung tissues of mice in the bleomycin group. It reduced later on. And the oxidation/antioxidation imbalance continued until the end of the model establishment. Obvious oxidation/antioxidation imbalance started on the 1st day in lung tissues of mice in the LPS group. However, this oxidation/antioxidation imbalance was adjusted back to normal level through time.