骨髓间充质干细胞移植对矽肺大鼠肺纤维化的作用

Effect of bone marrow mesenchymal stem cell transplantation on silicosis fibrosis in rats

目的探讨骨髓间充质干细胞(BMSCs)移植对矽肺大鼠肺组织纤维化的影响。方法将42只SD雌性大鼠分为A、B、C、D组。A、B和C组采用暴露式气管内一次性缓慢注入二氧化硅(SiO2)混悬液建立矽肺大鼠模型,D组则注入生理盐水。B、C组分别于造模后6h或第42天经尾静脉注射BMSCs。第14天,A、B和D组分别处死大鼠各6只,第56天各组分别处死6只。HE染色观察肺组织形态学变化,ELISA检测肺组织羟脯氨酸(Hyp)水平。结果 A组在造模后第14天,肺组织病理改变以急性炎症反应为主,第56天以纤维化为主;B、C组病理改变均较同时期A组轻;D组未见明显异常。肺组织中Hyp水平,A、B和C组均较D组明显升高(P=0.000);B、C组与A组比较,在BMSCs治疗后第14天均明显减低(P=0.000、0.035),B组在治疗后第56天仍明显减低(P=0.016)。结论不论在以肺泡炎为主还是在以纤维化为主的病理阶段予BMSCs移植,均可以延缓矽肺大鼠肺纤维化的病理进程。

Objective To study the effects of bone mesenchymal stem cells（BMSCs）transplantation on pulmonary tissue fibrosis in silicosis rats.Methods Forty-two healthy female SD rats were randomly divided into 4groups：group A,B,C and D.The group A,B and C received intratracheal injection of silica crystals（SiO2）to establish silicosis mouse models,while the group D received the infusion of physiological saline.BMSCs were injected by the tail vein at 6hafter modeling or on 42 din the group B and C.Six rats in each of group A,B,and D were sacrificed on 14 d,and other 6rats in each group were sacrificed on 56 day.The morphological changes of the lung tissues were observed by HE staining;the content of hydroxyproline（Hyp）in the lung tissue homogenate was detected by ELISA.Results The lung tissue pathological changes in the group A were dominated by acute inflammatory response on 14 dafter model construction,and fibrosis reaction on 56d;the pathological changes in the group B and C were lighter than those in the group A;while no obvious abnormality was found in the group D.The Hyp level of pulmonary tissue in the group A,B and C was significantly increased compared with the group D（P=0.000）;which on 14 dafter BMSCs treatment in the group B and C was significantly decreased compared with the group A（P=0.000,P=0.035）,and which on 56 dafter treatment in the group B was still significantly decreased（P=0.016）.Conclusion No matter in the pathological stages of pulmonary alveolitis and fibrosis,BMSCs transplantation may postpone the pathological process of pulmonary fibrosis in silicosis rats.