长期雾化吸入4种非雾化剂型药物对健康SD大鼠肺组织的影响
摘 要 目的：研究長期雾化吸入4种非雾化剂型药物对健康SD大鼠肺组织的损伤情况，评价其雾化吸入的安全性。方法：将40只健康SD大鼠（♂）按随机数字表法分为8组，分别为空白对照组、生理盐水组（溶剂对照）、布地奈德组（雾化剂型药物对照，0.1 g/L）、二氧化硅组（肺损伤药物对照，40 g/L）和4种非雾化剂型药物组[定喘汤组（15 g/mL，以生药量计）、头孢曲松组（200 g/L）、清开灵组（原液）和痰热清组（原液）]，每组5只。除空白对照组大鼠不作处理外，其余各组大鼠均雾化吸入给药，给药体积均为10 mL，每天给药2次，连续给药56 d。给药结束后，对其外周血中白细胞进行分类、计数以及对支气管肺泡灌洗液中白细胞进行计数；苏木精-伊红染色观察其肺组织病理变化并进行尘细胞计数；免疫组化法检测其肺组织中白细胞分化抗原163（CD163）表达水平。结果：各组大鼠外周血中白细胞分类主要有淋巴细胞和中性粒细胞，其中又以淋巴细胞为主。与空白对照组比较，生理盐水组大鼠外周血中白细胞、淋巴细胞、中性粒细胞计数和肺泡灌洗液中白细胞计数以及肺组织中尘细胞计数差异均无统计学意义（P>0.05）；支气管及肺组织结构完整，CD163表达为阴性。与生理盐水组比较，布地奈德组大鼠上述指标差异均无统计学意义（P>0.05），支气管及肺组织结构完整，CD163表达为阴性；而其余5组大鼠外周血中白细胞、淋巴细胞、中性粒细胞计数和支气管肺泡灌洗液中白细胞计数以及肺组织中尘细胞计数均显著升高（P<0.05）；肺组织发生不同程度的肺泡壁增厚、肺泡间质水肿等病理变化，CD163表达均为阳性或强阳性。结论：4种非雾化剂型药物长期雾化吸入后可引起健康SD大鼠肺组织不同程度的病理改变，炎症细胞计数升高，肺泡中出现尘细胞。
关键词 雾化吸入；非雾化剂型药物；肺损伤；安全性；大鼠
Effects of Long-term Aerosol Inhalation of 4 Kinds of Non-aerosol Drugs to Lung Tissue of Healthy SD Rats
TANG Rongguo1，HE Qian1，FU Lei1，XU Changye1，WANG Xiujuan2，LI Xiong1，OU Weilin1（1.Dept. of Pediatrics， the Affiliated Hospital of Guilin Medical College， Guangxi Guilin 541001， China；2.Dept. of Clinical Laboratory， the Affiliated Hospital of Guilin Medical College， Guangxi Guilin 541001， China）
ABSTRACT OBJECTIVE： To study lung tissue injury induced by long-term aerosol inhalation of 4 kinds of non-aerosol drugs in healthy SD rats， and to evaluate the safety of aerosol inhalation of non-aerosol drugs. METHODS： Totally 40 healthy SD rats （♂） were randomly divided into 8 group， i.e. blank control group， normal saline group （solvent control）， budesonide group （non-aerosol drug control， 0.1 g/L） ，silicon dioxide group （lung injury drug control， 40 g/L）and 4 kinds of non-aerosol drugs [Dingchuan decoction group （15 g/mL， calculated by crude drug）， cefatriaxone group （200 g/L）， Qingkailing group （stoste） and Tangreqing group （stoste）]， with 5 rats in each group. Except that blank control group didn’t received any treatment， other groups received aerosol inhalation， 10 mL， twice a day， for consecutive 56 days. After medication， the number of white blood cells in peripheral blood were counted and classified， and the number of white blood cells in bronchus alveolar lavage fluid were counted. The pathological changes of lung tissue were observed by HE staining and the number of dust cells was counted. The expression of leukocyte differentiation antigen 163 （CD163） in lung tissue were determined by immunohistochemical method. RESULTS： The white blood cells in peripheral blood mainly included lymphocyte and neutrophil， of which lymphocyte is the main one. Compared with blank control group， there was no statistical significance in the number of white blood cells， lymphocyte or neutrophil in peripheral blood， the number of white blood cells in alveolar lavage fluid or the number of dust cells in lung tissue of rats in normal saline group （P>0.05）； the structures of bronchus and lung tissue were intact， and the expression of CD163 was negative. Compared with normal saline group， there was no statistical significance in the above indexed of rats in budesonide group（P>0.05）， the structures of bronchus and lung tissue were intact， and the expression of CD163 was negative， while the number of white blood cells， lymphocyte or neutrophil in peripheral blood， the number of white blood cells in alveolar lavage fluid or the number of dust cells in lung tissue of rats in other 5 groups were all increased significantly （P<0.05）； alveolar wall thickening and alveolar interstitial edema occurred in different degrees in lung tissue. The expression of CD163 was positive or strongly positive. CONCLUSIONS： The long-term aerosol inhalation of 4 kinds of non-aerosol drugs can induce pathological changes of lung tissue and increase the number of inflammatory cell and dust cell in alveolin in healthy SD rats.