关键词: 骨髓间充质干细胞, 肺动脉高压, 移植, 分流术

Abstract:

Objective: To establish the rat models of pulmonary hypertension by operation,and to explore the possible therapeutic effect of mesenchymal stem cells(MSCs) on pulmonary hypertension,and to clarify its possible mechanism.Methods: The MSCs were isolated,cultured and identified. Forty-elght rats were randomly divided into control,model,low dose of MSCs (MSCH), and high dose of MSCs (MSCL) groups. Except control group,the rats in other groups were used to establish pulmonary hypertension models by abdominal aorta inferior vena cava shunting.Eight weeks after treatment,the rats in MSCH and MSCL groups were treated with MSCs,and the rats in model group were treated with the same volume of saline.And 6 weeks later,the right ventricular systolic pressure(RVSP),mean right ventricular pressure(MRVP),mean pulmonary arterial pressure(MPAP) and ventriculus dexter index(VDI) of the rats in various groups were measured.The levels of nitric oxide (NO) and tumor necrosis factor-α (TNF-α) in serum and lung tissue of the rats were also tested.Q-PCR method was used to analyze the expression of NADPH mRNA in lung tissue of the rats.HE staining was recruited to test the morphology of lung tissue.Results: The MSCs were successfully isolated and grew well.According to the result of flow cytometry,the cells were MSCs and the purity was more than 85%.After treatment,compared with control group,the RVSP,MRVP,MPAP and VDI of the rats in model group were increased significantly (P<0.05),compared with model group,the MRVP and MPAP of the rats in MSCL and MSCH groups were significantly decreased (P<0.05),and the RVSP and VDI of the rats in MSCH group were decreased (P<0.05).Compared with control group,the NO and TNF-α levels in serum and lung tissue of the rats in model group were significantly increased (P<0.01);compared with model group,the NO and TNF-α levels in serum of the rats in MSCL and MSCH groups were significantly decreased(P<0.05),and the NO and TNF-α levels in lung tissue of the rats in MSCH group were decreased (P<0.01). Compared with control group,the expression level of NADPH mRNA of the rats in model group was up-regulated (P<0.01);compared with model group,the expression level of NADPH mRNA of the rats in MSCH group was down-regulated (P<0.01). The lung tissue injury of the rats in MSCL and MSCH groups was reduced,and no thickened lung wall was observed.Conclusion: MSCs have therapeutic effect on the pulmonary hypertension and they can inhibit the generation of NO and TNF-α. Its mechanism is related to inhibiting the expression of NADPH gene.

Key words: mesenchymal stem cells, pulmonary hypertension, bypass surgery, transplantation