脂肪间充质干细胞延迟干预对野百合碱诱发的肺动脉高压大鼠肺小动脉功能的影响

Effects of delayed intervention of adipose tissue-derived mesenchymal stem cells on function of pulmonary arterioles in monocrotaline-induced pulmonary hypertensive rats

    摘要
  • 摘要: 背景归巢于肺动脉高压(PAH)模型大鼠体内的脂肪间充质干细胞(ADMSC)能诱导分化为内皮样细胞,ADMSC延迟干预野百合碱诱导的PAH大鼠,可以显著改善肺小动脉重构。目的进一步观察ADMSC延迟干预对野百合碱诱导PAH大鼠肺小动脉功能的影响。方法从SD大鼠腹股沟皮下脂肪分离培养ADMSC。90只雄性SD大鼠随机分为正常对照组(n=30)、PAH组(野百合碱诱导,n=30)和ADMSC延迟干预组ADMSC-DI组(n=30),于野百合碱诱导后2周,经左颈外静脉一次性给予ADMSC(1×106)。于ADMSC移植后1、2、3周,导管法测定肺动脉平均压(MPAP),采用离体血管张力法检测肺小动脉的内皮依赖性舒张(EDdR)、非内皮依赖性舒张(EDiR)以及收缩功能。结果与对照组比较,腹腔注射野百合碱后3、4、5周,PAH组大鼠MPAP明显升高(26.9±0.9,n=10)比(14.8±1.0,n=10);(32.2±0.7,n=8)比(15.2±1.0,n=10);(36.3±0.8,n=8)比(15.5±1.0,n=10)mm Hg,均P<0.05,肺小动脉EDdR和EDiR明显减弱pD2(EDdR):(4.85±0.29)比(8.12±0.48);(3.22±0.61)比(7.93±0.50);(3.16±0.52)比(7.85±0.63);pD2(EDiR):(6.28±0.38)比(8.64±0.35);(5.40±0.55)比(8.58±0.41);(4.79±0.51)比(8.47±0.47);均P<0.05;与PAH组比较,ADMSC延迟移植后1、2、3周,ADMSC-DI组大鼠MPAP明显降低(17.7±1.1,n=10)比(26.9±0.9,n=10);(21.9±0.9,n=10)比(32.2±0.7,n=8);(22.4±0.9,n=10)比(36.3±0.8,n=8)mm Hg;均P<0.05,肺小动脉EDdR增强pD2(EDdR):(8.08±0.37)比(4.85±0.29);(6.21±0.67)比(3.22±0.61);(5.74±0.41)比(3.16±0.52)均P<0.05;肺小动脉EdiR也明显增强pD2(EDiR):(8.16±0.23)比(6.28±0.38);(7.01±0.30)比(5.40±0.55);(6.89±0.23)比(4.79±0.51);均P<0.05。ADMSC-DI组延迟移植后2、3周与延迟移植后1周比较,MPAP明显增高,肺小动脉EDdR和EDiR明显减弱。结论 ADMSC延迟干预可以有效降低野百合碱诱导大鼠的肺动脉高压,并改善受损的肺小动脉EDdR和EDiR。

     

    Abstract: Backgrouds Adipose-derived mesenchymal stem cells（ADMSC）homing to pulmonary arterial hypertensive（PAH）rats can be induced and differentiated into endothelial-like cells;and delayed intervention of ADMSC on monocrotaline-induced PAH rats can significantly attenuate pulmonary arteriolar remodeling. Objective This study was to investigate the effects of delayed intervention of ADMSC on function of pulmonary arterioles in monocrotaline-induced PAH rats. Methods ADMSC were isolated from inguinal subcutaneous adipose tissue of SD rats and cultured. Ninety male SD rats were randomly assigned into normal control（n=30）,PAH（induced by monocrotaline,n=30）and delayed intervention of ADMSC（ADMSC-DI,n=30）,ADMSC（1×106）were delivered via left external jugular vein 2weeks after monocrotaline inductiongroups. At the 1st,2nd,3rd week after transplantion of ADMSC,mean pulmonary arterial pressure（MPAP）was measured by catheterization,pulmonary arteriolar endothelium-dependent relaxation（EDdR）,endothelium-independent relaxation（EDiR）and vasoconstriction were evaluated by isolated vascular ring tension. Results Compared with control group,at the 3rd,4th,5th week after intraperitoneal injection of monocrotaline,MPAP of PAH group were significantly increased（26.9±0.9,n=10）vs（14.8±1.0,n=10）;（32.2±0.7,n=8）vs（15.2±1.0,n=10）;（36.3±0.8,n=8）vs（15.5±1.0,n=10）mm Hg,all P＜0.05,pulmonary arteriolar EDdR and EDiR were markedly decreasedpD2（EDdR）:（4.85±0.29）vs（8.12±0.48）,（3.22±0.61）vs（7.93±0.50）,（3.16±0.52）vs（7.85±0.63）;pD2（EDiR）:（6.28±0.38）vs（8.64±0.35）;（5.40±0.55）vs（8.58±0.41）;（4.79±0.51）vs（8.47±0.47）;all P＜0.05. Compared with PAH group,at the 1st,2nd,3rd week after delayed transplantation of ADMSC,MPAP of ADMSC-DI group were significantly decreased（17.7±1.1,n=10）vs（26.9±0.9,n=10）;（21.9±0.9,n=10）vs（32.2±0.7,n=8）;（22.4±0.9,n=10）vs（36.3±0.8,n=8）mm Hg,all P＜0.05,pulmonary arteriolar EDdR were significantly increasedpD2（EDdR）:（8.08±0.37）vs（4.85±0.29）,（6.21±0.67）vs（3.22±0.61）,（5.74±0.41）vs（3.16±0.52）;all P＜0.05;and EDiR were also markedly increasedpD2（EDiR）:（8.16±0.23）vs（6.28±0.38）,（7.01±0.30）vs（5.40±0.55）,（6.89±0.23）vs（4.79±0.51）;all P＜0.05. Compared with those at the 1st week after delayed transplantation of ADMSC,MPAP were markedly increased,while EDdR and EDiR were obviously decreased at the 2nd and 3rd week. Conclusion Delayed intervention of ADMSC can effectively reduce pulmonary arterial pressure of monocrotaline-induced PAH rats,and improve the impaired pulmonary arteriolar EDdR and EDiR.

     

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