The protective effect of exogenous bone marrow mesenchymal stem cells on pulmonary fibrosis induced by paraquat

Abstract

Objective To explore the protective effect and possible mechanism of bone marrow mesenchymal stem cells(BMSCs) on pulmonary fibrosis induced by paraquat (PQ) in rats. Methods A total of 54 male SD rats were randomly(random number) divided into 3 groups(n=18 in each). Group A(normal control group), group B[PQ+ phosphate buffer solution(PBS)], group C(PQ+ BMSCs group). Rats in group B and C were induced to get pulmonary fibrosis by intragastric administration of PQ in a dosage of 120 mg/kg.In addition, BMSCs was given to rats in group C by injection in a dose of 1×106/mL via the vena caudalis, whereas an equal volume of PBS(1 mL)was given to rats in group B by injection instead.The survival rats in each groups were sacrificed separately at 7 days, 14 days and 28 days after administration of PQ.The lower lobe of left lung were taken to observe histopathological changes with HE staining and Masson staining, and the pulmonary fibrosis was scored by using the Szapiel classification of alveolitis. At the same time, the lower lobe of right lung was harvested to detect the hydroxyproline (HYP), TGF-β1 and HGF in lung tissue by using immunohistochemistry. Results The pathological changes in lung tissue of rats were inflammatory change in alveoli space filled with massive amount of exudate obviously in group B at 7 days after exposure to PQ, but in group C, the inflammatory changes were much milder than those in group B. The exudation and edema in lunge alveoli were mitigated in group B at 14 days after exposure to PQ, but pulmonary interstitial fibers were increased. The degree of pulmonary interstitial fibrosis in group C was milder than that in group B. In group B, there were obvious pathological changes including destroyed alveoli septum, enlarged alveoli, thickened alveoli septum and the deposition of collagen fibers, disarranged alveolar structure at 28 days after exposure to PQ. The deposition off collagen fiber was slighter with well observed basic alveolar structure in group C than that in group B. The levels of HYP in lung tissue at different intervals in B group were escalating with time after exposure to PQ, and reached a peak at 28 day, which were significantly higher than those in group A (P 0.05). The levels of HGF at different intervals in group B were little bit higher than those in group A, but there was no significant difference between them (P>0.05). The levels of HGF at different intervals in group C increased with time with significant differences among different intervals (P<0.05). The levels of HGF at 3 intervals in group C were significantly different from those of group A and group B group (P<0.05). Conclusions BMSCs can alleviate pulmonary fibrosis induced by PQ, and increase the survival rate, which may be attributed to decreasing the level of TGF-β1 and increasing the level of HGF. Key words: Bone marrow mesenchymal stem cells; Paraquat; Pulmonary; Fibrosis; TGF-β1; Hepatocyte growth factor