携分泌型白细胞蛋白酶抑制因子的间充质干细胞对慢性阻塞性肺疾病大鼠的治疗作用

目的 研究携分泌型白细胞蛋白酶抑制因子( SLPI)骨髓间充质干细胞(BMSCs)对慢性阻塞性肺疾病(COPD)大鼠气道炎症和黏液分泌的影响.方法 SD大鼠60只按随机数字表法随机分为阴性对照组、COPD模型组、BMSCs组和携SLPI质粒BMSCs组各15只,采用熏香烟加气管内注入内毒素法制备COPD模型,通过尾静脉注入BMSCs或携SLPI质粒BMSCs细胞.Western印迹检测SLPI表达,酶联免疫吸附法检测白细胞介素8(IL-8)和肿瘤坏死因子α(TNF-α)表达,通过病理切片观察杯状细胞增生情况.结果 携SLPI质粒BMSCs组支气管/肺组织中SLPI表达为(0.79±0.06),显著高于阴性对照组的(0.24±0.02),(P＜0.05).BMSCs组和携SLPI质粒BMSCs组支气管肺泡灌洗液中炎性因子IL-.8、TNF-α浓度均低于COPD模型组(均P＜0.05)；携SLPI质粒BMSCs组更低,分别为(17.6±1.7)和(36.6±4.0)ng/L,显著低于BMSCs组(均P＜0.05).携SLPI质粒BMSCs组支气管杯状细胞数较COPD模型组和BMSCs组明显减少(均P＜0.05).结论 携SLPI质粒BMSCs移植能够减轻COPD大鼠气道炎症和黏液分泌,有望用于对COPD患者的治疗.

Effects of secretary leukocyte protease inhibitor-transfected bone marrow mesenchymal stem cells on airway inflammation and mucus secretion in chronic obstructive pulmonary disease

Objective To explore the effects of secretary leukocyte protease inhibitor (SLPI)-transfected bone marrow mesenchymal stem cells (BMSCs) transplantation on airway inflammation and mucus secretion in chronic obstructive pulmonary disease (COPD) rats.Methods Sixty rats were equally and randomly divided into negative contol,COPD model,BMSCs and SLPI-transfected BMSCs groups.The COPD rat model was established in all rats with the exception of the negative control rats by smoking and intratracheal instillation of lipopolysaccharide (LPS). BMSCs with or without transfection of plasmid containing SLPI gene were delivered through caudal vein of rats at 30 days post-induction.The expression of SLPI was examined with Western blot.The levels of interleukin (IL)-8 and tumor necrosis factor (TNF)-α were detected by enzyme-linked immunosorbent assay (ELISA).Goblet cell hyperplasia of lung pathological section was observed on. Results Compared with the negative control group,the expression of SLPI increased significantly after the administration of SLPI-transfected BMSCs (0.79 ± 0.06 vs 0.24 ± 0.02,P＜0.05).The levels of IL-8 and TNF-α in BMSCs and SLPI-transfected BMSCs group were lower than those in the COPD model group. Compared with the negative control group,the administration of SLPI-transfected BMSCs resulted in a further decrease in IL-8 and TNF-α in bronchoalveolar lavage fluid ( 17.6 ± 1.7 ) vs ( 36.6 ± 4.0 ) ng/L,P ＜ 0.05 ].SLPI-transfected BMSCs transplantation also significantly attenuated goblet cell hyperplasia in rats ( P ＜ 0.05 ).Conclusion There is a potential role for cell-based SLPI gene therapy in the treatment of COPD.