Effects Of Adipose Tissue-derived Mesenchymal Stem Cells On Monocrotaline-induced Pulmonary Arterial Remodeling In Rats

ObjectiveTo investigate the effects of adipose-derived mesenchymal stem cells(ADMSC)on monocrotaline-induced pulmonary arterial hypertension and remodeling in rats.MethodsADMSC were obtained from rat Subcutaneous adipose of rat,s groin and is isolated by collagenase type I, and it was infected by Adenoviral vector transfeted with green fluorescent protein(GFP)before administrated。Ninety Sprague-Dawley rats were randomly assigned to three groups: normal control (Ctr), pulmonary arterial hypertension (PAH), ADMSC treated groups。The rats were given a dose of 40mg/Kg monocrotaline intraperitoneally in PAH and ADMSC,and Ctr rats were given 1ml normal saline intraperitoneally as control。ADMSC labeled with GFP(1X10~6/1ml) were delivered to rats by injection into left the jugular vein 2 wk after administration of monocrotaline and 1 ml normal saline was did in group PAHand control。1,2,3 weeks after ADMSC administrated, mean of pulmonary arterial pressure were measured by catheterization and right ventricular hypertrophy index were measured[RVHI%=RV/(LV+S)], and WT% and WA% of pulmonary arterioles were evaluated by ipp6.0 Image Analysis Software.Results(1)every point of ADMSC treated ,MPAP and RVHI% were significantly higher in PAH, as compared with Ctr group[MPAP(mmHg): (24.53±2.90) VS (14.81±1.95),(33.18±2.30)VS(15.08±2.35),(36.38±3.28)VS(15.65±2.27);RVHI%:(41.01±1.29)VS(28.25±2.15),(48.75±2.13)VS(28.71±2.08),(50.52±1.49)VS(28.54±2.19);P<0.05 respectively]。MPAP and RVHI% were significantly decreased after treatment of ADMSC[MPAP(mmHg): (18.63±2.15) VS(24.53±2.90),(23.07±2.84)VS(33.18±2.30),(22.98±2.34)VS(36.38±3.28);RVHI%:(36.21±4.27)VS(41.01±1.29),(39.47±4.02)VS(48.75±2.13), (41.02±0.93)VS(50.52±1.49);P<0.05 respectively]。(2)every point of ADMSC treated ,WA% and WT% were significantly increased in PAH, in comparison with Ctr group[WA%: (68.70±3.43) VS (50.27±4.92),(80.48±6.19)VS(51.61±3.29),(84.01±2.76)VS(52.02±5.87);WT%:(46.09±4.70)VS(32.46±5.19),(57.26±4.32)VS(32.52±3.19),(64.64±3.86)VS(31.42±4.53),P<0.05 respectively]. Administration of ADMSC [WA % : (58.23±4.08) VS(68.70±3.43) ,( 62.97±6.58 ) VS(80.48±6.19),(65.27±5.45)VS(84.01±2.76);WT%:(38.06±4.15)VS(46.09±4.70),(40.91±5.24)VS(57.26±4.32), (41.91±5.16)VS(64.64±3.86),P<0.05 respectively].(3)ADMSC treated 2 Week and 3 Week, MPAP,RVHI%,WA%和WT% were significantly increased, as compared with ADMSC treated 1 Week[MPAP(mmHg):(23.07±2.84),(22.98±2.34)VS (18.63±2.15);RVHI%:(39.47±4.02),(41.02±0.93)VS(36.21±4.27);WA%:(62.97±6.58),(65.27±5.45)VS (58.23±4.08) ;WT%:(40.91±5.24),(41.91±5.16)VS(38.06±4.15);P <0.05 respectively]。And ADMSC treated 2 Week compared with ADMSC treated 3 Week, MPAP,RVHI%,WA%和WT% were not considered statistically significant[MPAP(mmHg):(23.07±2.84)VS(22.98±2.34);RVHI%:(39.47±4.02)VS(41.02±0.93);WA%:(62.97±6.58)VS(65.27±5.45);WT%:(40.91±5.24)VS(41.91±5.16);P>0.05 respectively ].(4)ADMSC labeled with GFP were observed that they may survive in lung detected by fluorescence microscope。ConclusionsPulmonary arterial pressure was reduced and right ventricular hypertrophy and pulmonary arterioles remodeling were attenuated by ADMSC transplanted in monocrotaline-induced pulmonary hypertensive rats. The delevolpment of MCT-induced PH was only delayed when ADMSC treated 1 Week,but after ADMSC treated 2 Week,the therapeutic action of ADMSC was stable,there were not further development。...