骨髓间充质干细胞移植对百草枯所致急性肺损伤治疗的研究

Effect of transplantation of bone marrow mesenchymai stem cells on treatment of acute lung injury induced by paraquat

目的探讨骨髓间充质干细胞（BM-MSC）移植对百草枯所造成大鼠急性肺损伤的治疗效果。方法分离培养大鼠BMMSC，应用流式细胞技术及向成骨诱导分化来鉴定BM-MSC，大鼠48只，3只用于制备BMMSC，剩余45只随机分为5组，每组9只。A组为正常对照组，B、C、D、E四组使用百草枯腹腔注射诱导造成肺损伤模型。造模成功后B组注射生理盐水作为急性肺损伤模型对照组，C组按0．5mg／k的剂量注射地塞米松，D组于大鼠尾静脉注射BM-MSC悬浮液2ml（细胞数1×10^5），E组注射BM-MSC悬浮液和地塞米松。全部大鼠于治疗72h后处死，取左下肺计算肺组织湿干比，左上肺组织甲醛固定HE染色观察病理变化。取右肺组织测定肺组织匀浆中超氧化物歧化酶（SOD）、谷胱甘肽过氧化物酶（GSH-PX）的活性及丙二醛（MDA）含量。结果B组肺湿干比值升高提示肺水肿的存在，病理切片显示肺组织出现典型的急性肺损伤改变；与A组比较，B组SOD、GSH-PX活性均降低，MDA含量均增高（P值均〈0．01）。C、D组病理结果显示肺组织病理变化较轻；与B组比较，C、D组SOD、GSH—PX活性增高，MDA含量、肺湿干比则降低（P值均〈0．05或0．01）。E组情况好于C、D组。结论BM-MSC移植可减轻百草枯诱导的大鼠急性肺损伤，与糖皮质激素联合效果更佳。

Objective To investigate the effects of transplantation of bone marrow mesenchymal stem cells （BM MSC） on the treatment of acute lung injury induced by paraquat. Methods Rat BM-MSC isolated and cultured were identified by flow eytometry and osteogenic differentiation. In 48 rats,three rats were used for the preparation of BM-MSC,the remaining 45 rats were randomly divided into five groups,nine were in each group. Group A was normal control group,group B,C,D,and E were injected intraperitoneally with paraquat to induce lung injury model. After the modeling,group B received normal saline as acute lung injury model group,group C received 0. 5 mg/kg dexamethasone,group D was injected with 2 ml BM-MSC suspension （1 ×10^5 cells） by tail vein,and group E was injected with BM-MSC suspension and dexamethasone. All rats were killed at 72 h after treatment, the left lower lung was taken to calculate wet to dry ratio of lung, the left top lung tissue was fixed to observe pathological changes by HE staining. The right lung tissue was taken to determinate superoxide dismutase （SOD）, glutathione peroxidase （GSH PX） activity and malondialdehyde （MDA） content. Results In group B, lung wet to dry ratio increased, which showed pulmonary edema, and the pathological result showed typical changes of acute lung injury. Compared with group A,the activity of SOD and GSH-PX decreased, MDA level increased in group B（all P 〈 0.01）. In group C and D, pathological changes of lung tissue were not obvious. Compared with group B, the activity of SOD and GSH PX increased,lung wet to dry ratio and MDA level decreased（ P 〈0.05 or P〈0.01）. The parameters in group E were better than those in group C and D. Conclusions BM-MSC transplantation canreduce paraquat-induced acute lung injury,have better effect combined with glueoeortieoids.