CXCR4高表达骨髓间充质干细胞对百草枯中毒肺损伤大鼠的治疗作用

Effect of Highly Expressed CXCR4 Bone Marrow Mesenchymal Stem Cell on Lung Injury Induced by Paraquat Poisoning in Rats

目的观察CXC趋化因子受体4(CXC chemokine receptor 4,CXCR4)高表达的骨髓间充质干细胞(bone marrow mesenchymal stem cell,BMSC)对百草枯中毒致急性肺损伤大鼠的治疗作用。方法建立BMSC-CXCR4细胞株。制备并鉴定百草枯中毒致急性肺损伤大鼠模型。将成年雄性SD大鼠随机分为4组:生理盐水组、BMSC治疗组(BMSC组)、BMSC-CXCR4治疗组(BMSC-CXCR4组)和5%O2低氧培养的BMSC-CXCR4治疗组(BMSCCXCR4+5%O2组),于4组大鼠尾静脉给予不同处理后,比较各组血清中白介素-1β(IL-1β)、肿瘤坏死因子-α(TNF-α)和超氧化物歧化酶(SOD)活性变化,并观察肺组织病理变化。结果成功构建稳定转染BMSC-CXCR4细胞株。急性肺损伤大鼠肺组织可见肺泡大片融合,肺泡结构明显破坏;与对照组比较,实验组随着时间延长动脉血氧分压持续下降,肺湿干比持续升高,血清IL-1β、TNF-α水平持续升高,SOD活性持续下降(P<0.05,P<0.01)。百草枯中毒致急性肺损伤12 h时,BMSC治疗组、BMSC-CXCR4组和BMSC-CXCR4+5%O2组大鼠血清IL-1β和TNF-α水平均低于生理盐水组,SOD活性高于生理盐水组,且BMSC-CXCR4+5%O2组优于BMSC组和BMSC-CXCR4组(P<0.01)。急性肺损伤12 h时,与生理盐水组比较,各治疗组大鼠肺泡形态大致完整,肺泡壁比较光滑;其中BMSC-CXCR4+5%O2组最接近于正常肺组织。结论低氧培养的BMSC-CXCR4对百草枯中毒致急性肺损伤具有良好的治疗作用。

Objective To investigate effect of highly expressed chemokine receptor 4 （CXCR4） bone marrow mesenchymal stem cell （BMSC-CXCR4）in treatment of acute lung injury （ALI） induced by paraquat poisoning in rats. Methods BMSC-CXCR4 cell line was established. Rat models of acute lung injury induced by paraquat poisoning were established and identified. Adult male SD rats of successful establishment were randomly divided into normal saline control （NC） group, BMSC treatment （BMSC） group, BMSC-CXCR4 treatment （BMSC-CXCR4） group and BMSC-CXCR4 ＋ 5% 02 treatment （BMSC-CXCR4 ＋ 5% 02 ） group. All the rats received different treatments through caudal vein. Among the 4 groups, changes of serum interleukin-1β（ IL-1β）, tumor necrosis factor-α （ TNF-α）, and superoxide dismutase （ SOD ） activity were compared, and pathological changes in lung tissues were observed. Results The stably transfected BMSC- CXCR4 was established successfully. A large of fusion of pulmonary alveoli was found in lung tissues of ALI rats, and construction of pulmonary alveoli was destroyed obviously. Compared with those in NC group, partial pressure of oxygen in artery （PaO2 ） levels persistently decreased, and dry/wet ratio of lung persistently increased, and serum IL-1 β and TNF-α levels persistently increased, while SOD activities persistently decreased with prolonging time in treatment groups （P 〈 0. 05, P 〈0.01 ）. In 12h after ALI induced by paraquat poisoning, serum IL-1β and TNF-α levels were significantly decreased, and serum SOD activities were significantly increased in BMSC-CXCR4 and BMSC-CXCR4 ＋ 5% O2 groups compared with those in NC group; serum IL-1β and TNF-α levels in BMSC-CXCR4 ＋ 5% O2 group were significantly decreased compared with those in BMSC and BMSC-CXCR4 groups （P 〈 0.01）. In 12 h after ALI, compared with those in NC group, alveolus appearances were completed generally, and alveolar walls were smooth in treatment groups; the pathological findings in lungs of BMSC-CXCR4 ＋ 5% O2 group were the closest to normal lung tissues. Conclusion The hypoxic cul- tured BMSC-CXCR4 has good therapeutic effect on acute lung injury induced by paraquat poisoning in rats.