Objective:To study the influence of bone marrow mesenchymal stem cells(MSCs)transplantation on hypoxic pulmonary hypertension(HPH)in rats.Methods:MSCs in SD rats were separated,cultivated,identified in vitro,and label...Objective:To study the influence of bone marrow mesenchymal stem cells(MSCs)transplantation on hypoxic pulmonary hypertension(HPH)in rats.Methods:MSCs in SD rats were separated,cultivated,identified in vitro,and labeled by the green fluorescence protein(GFP)adenovirus.Healthy male SD rats were randomly divided into four groups:normal control group(NC group)and HPH group,with eight rats in each group respectively;HPH+mesenchymal stem cell transplantation group(MSCs group)and HPH+vascular endothelial growth factor+mesenchymal stem cell transplantation group(VEGF+MSCs group),with twenty-four rats in each group respectively.In this experiment,intermittent normobaric hypoxia was employed to establish the pulmonary hypertension rat models,with stem cells transfected and transplanted.The mean pulmonary artery pressure(mPAP)was observed in rats to calculate the right ventricular hypertrophy index(RVHI);the morphological changes of pulmonary arterioles in each group of rats were observed under the microscope;the distribution and manifestation of MSCs fluorescently labeled by adenovirus transfection were observed in pulmonary arterioles under the fluorescence microscope at the set time points of 7 d,14 d and 28 d after the transplantation of stem cells.Results:For NC group,the mPAP(mmHg)was 15.5±1.5 at 28 d,while the mPAP in HPH,MSCs and VEGF+MSCs groups were 26.1±1.9,21.6±2.7 and 20.1±2.9 respectively which were apparently higher than that in NC group(p<.01).Compared with HPH group(p<.01),the mPAP was obviously decreased in MSCs and VEGF+MSCs groups.There was no significant difference between MSCs and VEGF+MSCs groups.At 28 d,RVHI for NC group was 0.28±0.02,while the RVHI in HPH,MSCs and VEGF+MSCs groups were 0.43±0.07,0.34±0.03 and 0.35±0.01 respectively which were apparently higher than that in NC group(p<.01).In comparison with HPH group,RVHI was significantly decreased in MSCs and VEGF+MSCs groups(p<.05).There was no significant difference between MSCs and VEGF+MSCs groups.For HPH group,at 28 d,pulmonary arterioles were apparently thickened,with luminal stenosis&obliteration and incomplete endothelial cells.Compared with HPH group,pulmonary arterioles in MSCs group became thinning,with the lumen unobstructed and the integrity of endothelial cells improved.The changes in the manifestation of MSCs and VEGF+MSCs groups were not significant.Conclusions:The transplantation of MSCs can improve the remodeling of pulmonary arterioles to partially reverse the progress of HPH;the combined transplantation of VEGF and MSCs doesn’t improve the effect of MSC transplantation.展开更多
背景:目前正在兴起的干细胞治疗技术及基因修饰技术有可能在肺动脉高压治疗中获得独特疗效。目的:探讨携带碱性成纤维细胞生长因子基因的骨髓间充质干细胞移植对肺动脉高压大鼠血流动力学水平的影响。方法:选择3周龄SD雄性大鼠,于体外...背景:目前正在兴起的干细胞治疗技术及基因修饰技术有可能在肺动脉高压治疗中获得独特疗效。目的:探讨携带碱性成纤维细胞生长因子基因的骨髓间充质干细胞移植对肺动脉高压大鼠血流动力学水平的影响。方法:选择3周龄SD雄性大鼠,于体外进行骨髓间充质干细胞培养及纯化,在腺病毒介导下实施基因转染,使碱性成纤维细胞生长因子基因成功导入骨髓间充质干细胞。将60只SD大鼠给予野百合碱腹腔注射(50 mg/kg)进行肺动脉高压模型复制,随机分成3组,其中肺动脉高压组于颈内静脉移植1 m L的L-DMEM培养基,骨髓间充质干细胞组于颈内静脉移植1 m L空腺病毒载体转染的骨髓间充质干细胞悬液,碱性成纤维细胞生长因子组于颈内静脉移植1 m L腺病毒介导下碱性成纤维细胞生长因子转染骨髓间充质干细胞悬液。结果与结论:经3周治疗后,各组大鼠动脉血压差异无显著性意义(P>0.05);其中碱性成纤维细胞生长因子组大鼠的肺动脉收缩期压力和平均肺动脉压明显低于肺动脉高压组、骨髓间充质干细胞组,差异有显著性意义(P<0.05);各组大鼠右心室的肥大指数比较差异无显著性意义(P>0.05);碱性成纤维细胞生长因子组大鼠血浆内皮素1水平明显低于肺动脉高压组、骨髓间充质干细胞组,差异有显著性意义(P<0.05)。结果显示携带碱性成纤维细胞生长因子的骨髓间充质干细胞移植,能够改善肺动脉高压大鼠肺血管的血流动力学水平,保护机体血管的内皮细胞,并拮抗血管的收缩。展开更多
背景:随着干细胞移植治疗技术的发展及基因修饰技术的兴起为肺动脉高压的治疗提供了新的思路和方法。目的:观察人端粒酶反转录酶基因修饰人羊膜间充质干细胞移植对肺动脉高压大鼠的治疗效果。方法:66只成年雌性Wistar大鼠给予野百合碱...背景:随着干细胞移植治疗技术的发展及基因修饰技术的兴起为肺动脉高压的治疗提供了新的思路和方法。目的:观察人端粒酶反转录酶基因修饰人羊膜间充质干细胞移植对肺动脉高压大鼠的治疗效果。方法:66只成年雌性Wistar大鼠给予野百合碱腹腔注射(60 mg/kg)进行肺动脉高压模型复制,造模成功63只随机分成3组,其中肺动脉高压组于颈内静脉移植1 m L的L-DMEM培养基,人羊膜间充质干细胞组于颈内静脉移植1 m L人羊膜间充质干细胞悬液,人端粒酶反转录酶组于颈内静脉移植1 m L人端粒酶反转录酶转染人羊膜间充质干细胞悬液。移植后3周观察对比各组大鼠血流动力学、血浆内皮素1水平,以及右心室的肥大指数及心肌细胞凋亡情况。结果与结论:1治疗3周后各组间大鼠动脉血压差异无显著性意义(P>0.05);人端粒酶反转录酶组大鼠肺动脉收缩期压力和平均肺动脉压明显低于肺动脉高压组、人羊膜间充质干细胞组,差异有显著性意义(P<0.05)。2各组大鼠右心室的肥大指数差异无显著性意义(P>0.05)。3与肺动脉高压组及人羊膜间充质干细胞组相比,人端粒酶反转录酶组大鼠血浆内皮素1水平显著降低,差异有显著性意义(P<0.05)。4人端粒酶反转录酶组心肌细胞凋亡数较人羊膜间充质干细胞组和肺动脉高压组明显减少。5结果显示携带人端粒酶反转录酶基因的人羊膜间充质干细胞移植能够改善肺动脉高压大鼠的血流动力学异常状态,还可以保护机体血管内皮细胞,减少心肌细胞的凋亡。展开更多
文摘Objective:To study the influence of bone marrow mesenchymal stem cells(MSCs)transplantation on hypoxic pulmonary hypertension(HPH)in rats.Methods:MSCs in SD rats were separated,cultivated,identified in vitro,and labeled by the green fluorescence protein(GFP)adenovirus.Healthy male SD rats were randomly divided into four groups:normal control group(NC group)and HPH group,with eight rats in each group respectively;HPH+mesenchymal stem cell transplantation group(MSCs group)and HPH+vascular endothelial growth factor+mesenchymal stem cell transplantation group(VEGF+MSCs group),with twenty-four rats in each group respectively.In this experiment,intermittent normobaric hypoxia was employed to establish the pulmonary hypertension rat models,with stem cells transfected and transplanted.The mean pulmonary artery pressure(mPAP)was observed in rats to calculate the right ventricular hypertrophy index(RVHI);the morphological changes of pulmonary arterioles in each group of rats were observed under the microscope;the distribution and manifestation of MSCs fluorescently labeled by adenovirus transfection were observed in pulmonary arterioles under the fluorescence microscope at the set time points of 7 d,14 d and 28 d after the transplantation of stem cells.Results:For NC group,the mPAP(mmHg)was 15.5±1.5 at 28 d,while the mPAP in HPH,MSCs and VEGF+MSCs groups were 26.1±1.9,21.6±2.7 and 20.1±2.9 respectively which were apparently higher than that in NC group(p<.01).Compared with HPH group(p<.01),the mPAP was obviously decreased in MSCs and VEGF+MSCs groups.There was no significant difference between MSCs and VEGF+MSCs groups.At 28 d,RVHI for NC group was 0.28±0.02,while the RVHI in HPH,MSCs and VEGF+MSCs groups were 0.43±0.07,0.34±0.03 and 0.35±0.01 respectively which were apparently higher than that in NC group(p<.01).In comparison with HPH group,RVHI was significantly decreased in MSCs and VEGF+MSCs groups(p<.05).There was no significant difference between MSCs and VEGF+MSCs groups.For HPH group,at 28 d,pulmonary arterioles were apparently thickened,with luminal stenosis&obliteration and incomplete endothelial cells.Compared with HPH group,pulmonary arterioles in MSCs group became thinning,with the lumen unobstructed and the integrity of endothelial cells improved.The changes in the manifestation of MSCs and VEGF+MSCs groups were not significant.Conclusions:The transplantation of MSCs can improve the remodeling of pulmonary arterioles to partially reverse the progress of HPH;the combined transplantation of VEGF and MSCs doesn’t improve the effect of MSC transplantation.
文摘背景:目前正在兴起的干细胞治疗技术及基因修饰技术有可能在肺动脉高压治疗中获得独特疗效。目的:探讨携带碱性成纤维细胞生长因子基因的骨髓间充质干细胞移植对肺动脉高压大鼠血流动力学水平的影响。方法:选择3周龄SD雄性大鼠,于体外进行骨髓间充质干细胞培养及纯化,在腺病毒介导下实施基因转染,使碱性成纤维细胞生长因子基因成功导入骨髓间充质干细胞。将60只SD大鼠给予野百合碱腹腔注射(50 mg/kg)进行肺动脉高压模型复制,随机分成3组,其中肺动脉高压组于颈内静脉移植1 m L的L-DMEM培养基,骨髓间充质干细胞组于颈内静脉移植1 m L空腺病毒载体转染的骨髓间充质干细胞悬液,碱性成纤维细胞生长因子组于颈内静脉移植1 m L腺病毒介导下碱性成纤维细胞生长因子转染骨髓间充质干细胞悬液。结果与结论:经3周治疗后,各组大鼠动脉血压差异无显著性意义(P>0.05);其中碱性成纤维细胞生长因子组大鼠的肺动脉收缩期压力和平均肺动脉压明显低于肺动脉高压组、骨髓间充质干细胞组,差异有显著性意义(P<0.05);各组大鼠右心室的肥大指数比较差异无显著性意义(P>0.05);碱性成纤维细胞生长因子组大鼠血浆内皮素1水平明显低于肺动脉高压组、骨髓间充质干细胞组,差异有显著性意义(P<0.05)。结果显示携带碱性成纤维细胞生长因子的骨髓间充质干细胞移植,能够改善肺动脉高压大鼠肺血管的血流动力学水平,保护机体血管的内皮细胞,并拮抗血管的收缩。
文摘背景:随着干细胞移植治疗技术的发展及基因修饰技术的兴起为肺动脉高压的治疗提供了新的思路和方法。目的:观察人端粒酶反转录酶基因修饰人羊膜间充质干细胞移植对肺动脉高压大鼠的治疗效果。方法:66只成年雌性Wistar大鼠给予野百合碱腹腔注射(60 mg/kg)进行肺动脉高压模型复制,造模成功63只随机分成3组,其中肺动脉高压组于颈内静脉移植1 m L的L-DMEM培养基,人羊膜间充质干细胞组于颈内静脉移植1 m L人羊膜间充质干细胞悬液,人端粒酶反转录酶组于颈内静脉移植1 m L人端粒酶反转录酶转染人羊膜间充质干细胞悬液。移植后3周观察对比各组大鼠血流动力学、血浆内皮素1水平,以及右心室的肥大指数及心肌细胞凋亡情况。结果与结论:1治疗3周后各组间大鼠动脉血压差异无显著性意义(P>0.05);人端粒酶反转录酶组大鼠肺动脉收缩期压力和平均肺动脉压明显低于肺动脉高压组、人羊膜间充质干细胞组,差异有显著性意义(P<0.05)。2各组大鼠右心室的肥大指数差异无显著性意义(P>0.05)。3与肺动脉高压组及人羊膜间充质干细胞组相比,人端粒酶反转录酶组大鼠血浆内皮素1水平显著降低,差异有显著性意义(P<0.05)。4人端粒酶反转录酶组心肌细胞凋亡数较人羊膜间充质干细胞组和肺动脉高压组明显减少。5结果显示携带人端粒酶反转录酶基因的人羊膜间充质干细胞移植能够改善肺动脉高压大鼠的血流动力学异常状态,还可以保护机体血管内皮细胞,减少心肌细胞的凋亡。
