摘要目的 通过研究不同药物雾化吸入对SD大鼠肺组织的影响,探索非雾化剂型药物用于雾化的安全性.方法 无特定病原体(SPF)级健康雄性SD大鼠40只随机分为空白对照组、9 g/L盐水组、沙丁胺醇组、定喘汤组、双黄连组、庆大霉素组、丹参组、二氧化硅组共8组(5只/组).每天雾化2次,持续56 d.取外周血、支气管肺泡灌洗液(BALF)进行细胞计数与分类.左肺中叶切片HE染色观察肺组织病理变化并计数尘细胞数目,免疫组织化学法检测CD163表达水平.结果 1.外周血白细胞计数:空白对照组[(3. 96 ± 0. 36)× 109/L]、9 g/L盐水组[(4. 66 ± 0. 58)×109/L]、沙丁胺醇组[(4. 06 ± 0. 86)×109/L]、定喘汤组[(8. 98 ± 1. 08)×109/L]、双黄连组[(7. 10 ± 0. 88)×109/L]、庆大霉素组[(6. 14 ± 0. 89)×109/L]、丹参组[(9. 84 ± 2. 33)×109/L]、二氧化硅组[(8. 99 ± 2. 48)×109/L],8组间比较差异有统计学意义( F＝14. 530,P<0. 05);空白对照组、9 g/L盐水组、沙丁胺醇组间比较差异均无统计学意义(均P>0. 05).BALF白细胞计数:空白对照组[(2. 16 ± 1. 04)×109/L]、9 g/L盐水组[(3. 94 ± 0. 67)×109/L]、沙丁胺醇组[(4. 36 ± 1. 15)×109/L]、定喘汤组[(14. 58 ± 2. 93)×109/L]、双黄连组[(19. 68 ± 6. 29)×109/L]、庆大霉素组[(11. 74 ± 1. 03)×109/L]、丹参组[(44. 75 ± 10. 8)×109/L]、二氧化硅组[(53. 54 ± 14. 25)×109/L],8组间比较差异有统计学意义( F＝40. 616,P<0. 05);空白对照组、9 g/L盐水组、沙丁胺醇组间比较差异均无统计学意义(均P>0. 05).BALF淋巴细胞计数:空白对照组[(18. 70 ± 9. 00)×108/L]、9 g/L 盐水组[(36. 01 ± 5. 99)×108/L]、沙丁胺醇组[(38. 95 ± 11. 69)×108/L]、定喘汤组[(132. 70 ± 26. 94)×108/L]、双黄连组[(173. 56 ± 57. 6)×108/L]、庆大霉素组[(106. 60 ± 16. 76)×108/L]、丹参组[(340. 63 ± 70. 97)×108/L]、二氧化硅组[(495. 63 ± 131. 95)× 108/L],8组间比较差异有统计学意义( F＝41. 980,P<0. 05);空白对照组、9 g/L盐水组、沙丁胺醇组间比较差异均无统计学意义(均 P >0. 05).2. HE 染色尘细胞计数:空白对照组( 12 个/10 HP)、9 g/L 盐水组(26个/10 HP)、沙丁胺醇组(17个/10 HP)、定喘汤组(262个/10 HP)、双黄连组(133个/10 HP)、庆大霉素组(109个/10 HP)、丹参组(96 个/10 HP)、二氧化硅组(315 个/10 HP),8 组间比较差异有统计学意义( F ＝69. 915,P<0. 05);空白对照组、9 g/L盐水组、沙丁胺醇组间比较差异均无统计学意义(均P>0. 05).3. HE染色:空白对照组、9 g/L盐水组、沙丁胺醇组肺组织结构完整,其他组均有不同程度肺损伤.4.免疫组织化学染色:空白对照组、9 g/L盐水组、沙丁胺醇组呈阴性,定喘汤组、双黄连组、庆大霉素组、丹参组、二氧化硅组均呈不同程度阳性.结论 9g/L盐水、沙丁胺醇用于雾化吸入不会造成肺组织损伤;非雾化剂型药物长期用于雾化可造成SD大鼠肺组织损伤,严重程度因具体药物而不同.

abstractsObjective To have SD rats inhaled with different drugs,and observe their lung pathological change of lungs through light microscopy,in order to evaluate the safety of different drugs inhaled by natural rats. Methods A total of 40 rats were randomly divided into 8 groups,and every group had 5 rats,including blank control groups,9 g/L saline group,Salbutamol group,Dingchuantang group,Shuanghuanglian group,Centamicin group,Danshen group,Silicon dioxide group,twice a day,last 56 days totally. Then,blood and bronchoalveolar lavage fluid were collected and analyzed for cell count,percent of each type of cell,to measure the severity of the inflammation. Additionally,histopathology re-vealed the lungˊs pathological change and the number of dust cell;while immunohistochemistry revealed CD163 respon-ding. Results (1)White blood cell count:blank control group(3. 96 ± 0. 36)×109/L,9 g/L saline group(4. 66 ± 0. 58)×109/L,Salbutamol group(4. 06 ± 0. 86)×109/L,Dingchuantang group(8. 98 ± 1. 08)×109/L,Shuanghuang-lian group(7. 10 ± 0. 88)×109/L,Centamicin group(6. 14 ± 0. 89)×109/L,Danshen group(9. 84 ± 2. 33)×109/L, Silicon dioxide group(8. 99 ± 2. 48)×109/L,and comparative analysis of the 8 groups had significant difference(F＝14. 530,P<0. 05);the differences among blank control group,9 g/L saline group and Salbutamol group were not sig- nificant(all P>0. 05). White cell count in BALF:blank control group(2. 16 ± 1. 04)×109/L,9 g/L saline group (3. 94 ± 0. 67)×109/L,Salbutamol group(4. 36 ± 1. 15)×109/L,Dingchuantang group(14. 58 ± 2. 93)×109/L, Shuanghuanglian group(19. 68 ± 6. 29)×109/L,Gentamicin group(11. 74 ± 1. 03)×109/L,Danshen group(44. 75 ± 10. 8)×109/L,Silicon dioxide group(53. 54 ± 14. 25)×109/L,and comparative analysis of the 8 groups had signifi-cant difference(F＝40. 616,P<0. 05);the differences among blank control group,9 g/L saline group and Salbutamol group were not significant(all P>0. 05). Lymphocyte count in BALF:blank control group(18. 70 ± 9. 00)×108/L, 9 g/L saline group( 36. 01 ± 5. 99 )×108/L,Salbutamol group( 38. 95 ± 11. 69 )×108/L,Dingchuantang group (132. 70 ± 26. 94)×108/L,Shuanghuanglian group(173. 56 ± 57. 6)×108/L,Gentamicin group(106. 60 ± 16. 76)× 108/L,Danshen group(340. 63 ± 70. 97)×108/L,Silicon dioxide group(495. 63 ± 131. 95)×108/L,and comparative analysis of the 8 groups had significant difference(F＝41. 980,P<0. 05);the differences among blank control group, 9 g/L saline group and Salbutamol group were not significant(all P>0. 05).(2)Number of lung dust cell count in 10 sight of high light microscopy:blank control group 12/10 HP,9 g/L saline group 26/10 HP,Salbutamol group 17/10 HP,Dingchuantang group 262/10 HP,Shuanghuanglian group 133/10 HP,Gentamicin group 109/10 HP,Danshen group 96/10 HP,Silicon dioxide group 315/10 HP,and comparative analysis of the 8 groups had significant difference (F＝69. 915,P<0. 05);the differences among blank control group,9 g/L saline group and Salbutamol group were not significant(all P>0. 05).(3)Hematoxylin-eosin staining of lung:blank control group,9 g/L saline group and Sal-butamol group had no pathological change in the lung,but Salbutamol group,Dingchuantang group,Shuanghuanglian group,Gentamicin group,Danshen group and Silicon dioxide group had pathological changes in different degrees.(4) Immunohistochemistry of CD163 responding:blank control group,9 g/L saline group and Salbutamol group had negative expression,Salbutamol group,Dingchuantang group,Shuanghuanglian group,Gentamicin group,Danshen group and Sili-con dioxide group had positive expression in different degrees. Conclusions 9 g/L saline,salbutamol for atomized inhalation does not cause lung tissue damage;Long-term use of non-atomized drugs in atomization can cause lung tissue injury in SD rats,and the severity varies with specific drugs.