Effects Of Adipose Tissue-derived Mesenchymal Stem Cells On IL6, TNF-α And BNP In Monocrotaline-induced Pulmonary Artery Hypertensive Rats

Objective: To investigate effects of adipose tissue-derived mesenchymal stemcells （ADMSC） on IL6,TNF-α,BNP in pulmonary artery hypertension(PAH)induced by monocrotaline(MCT) in rats.Methods: ADMSC were obtained from subcutaneous adipose of rat，s groin andisolated by collagenase type I.Forty Sprague-Dawley rats were randomly assignedinto three groups：normal control (Ctr), PAH(ten rats were randomly drew materialsafter2weeks by given monocrotaline, the others were drew materials after5weeksby given monocrotaline),ADMSC-treated groups(ADMSC). A single dose of40mg/Kg monocrotaline intraperitoneally was given in PAH and ADMSC group.ADMSCs (1X106/ml) were delivered to rats by injection into left jugular vein2weeksafter administration of monocrotaline.Mean of pulmonary arterial pressure（mPAP）were measured by catheterization. Right ventricular hypertrophy index (RVHI) weremeasured by weighing method. ADMSC labeled with GFP were observed byfluorescence microscope in lung. WT%and WA%of pulmonary arterioles wereevaluated by ipp6.0Image Analysis Software.IL-6, TNF-α and BNP were measuredby ELISA.Result:1) ADMSCs labeled with GFP were observed by fluorescence microscopethat they maybe survive in lung.2) MPAP was increased after MCT injection in time-dependent manner. There was no significant differences in mPAP between Ctr and PAH2W group. MPAP wassignificantly higher in PAH5W, compared with Ctr or PAH2W. However, mPAP wasstrikingly decreased in ADMSC, compared with PAH5W[mPAP: Ctr(15.23±0.89) VSPAH2W(16.18±0.76)mmHg, P>0.05; PAH5W(33.39±0.92) VS Ctr(15.23±0.89),PAH2W(16.18±0.76)mmHg, P<0.05； ADMCS(19.91±0.0.83)mmHg VS PAH5W(33.39±0.92), P<0.05].3) Pulmonary artery wall was increased after MCT injection in time-dependentmanner. WA and WT were significantly higher in PAH5W or PAH2W, comparedwith Ctr. WA and WT were significantly difference in PAH5W, compared withPAH2W. However, WA and WT were strikingly decreased in ADMSC, comparedwith PAH5W[WT%:Ctr(30.66±3.69)VS PAH2W(39.29±4.53),PAH5W(56.18±4.79); PAH5W(56.18±4.79) VS PAH2W(39.29±4.53); PAH5W(56.18±4.79) VS ADMSC(42.09±4.89); WA%:Ctr(51.81±3.41)VS PAH2W(63.09±6.56),PAH5W(80.13±6.89); PAH5W(80.13±6.89) VS PAH2W(63.09±6.56); PAH5W(80.13±6.89) VS ADMSC(66.12±7.36); P <0.05respectively].4) RVHI was increased after MCT injection in time-dependent manner. RVHI wassignificantly higher in PAH5W or PAH2W, compared with Ctr group. RVHI wassignificantly difference in PAH5W, compared with PAH2W. However, RVHI wasstrikingly decreased after treatment of ADMSC, compared with PAH5W[RVHI：Ctr(28.552.16) VS PAH2W(41.062.32), PAH5W(51.363.76); PAH5W(51.363.76) VS PAH2W(41.062.32); PAH5W(51.363.76) VS ADMCS(41.161.59); P <0.05respectively].5) IL-6, TNF-α and BNP were increased after MCT injection in time-dependentmanner. They was significantly higher in PAH5W or PAH2W, compared with Ctr.They was significantly difference in PAH5W, compared with PAH2W. However,they was strikingly decreased after treatment of ADMSC, compared with PAH5W[IL6:Ctr(98.30±11.98) VS PAH2W(143.63±6.71), PAH5W(218.34±19.87); PAH5W(218.34±19.87) VS ADMCS(148.35±2.38)pg/ml; TNF-α:Ctr(970.8953.79) VSPAH2W(1237.9953.61), PAH5W(1799.0356.89); PAH5W(1799.0356.89) VS ADMSC(1503.7540.67) pg/ml;BNP: Ctr(216.6037.19) VS PAH2W(286.2313.40), PAH5W(625.0714.65); PAH5W(625.0714.65) VSADMSC(468.2118.40) pg/ml, P <0.05respectively].Conclusions(1) ADMSC were delivered to rats by injection into left jugular vein may survived inlung detected.(2)Pulmonary arterial pressure was reduced, pulmonary arterioles remodeling andright ventricular hypertrophy were attenuated by ADMSC in monocrotaline-inducedpulmonary hypertensive rats.(3) IL-6and TNF-α were reduced by ADMSC in monocrotaline-induced pulmonaryhypertensive rats.(4) BNP was reduced by ADMSC in monocrotaline-induced pulmonary hypertensiverats.