Therapeutical Effect Of Mesenchymal Stem Cells Transplantation Through Tracheal Injection On Early Vascular Inflammation Induced Pulmonary Arterial Hypertension In Rats

Background Pulmonary arterial hypertension（PAH）, In the United States in2008DanaPoint southern California at the4th pulmonary hypertension meeting proposedthat in the resting state, through the right cardiac catheterization to determine PAH,mean pulmonary artery pressure≧25mmHg as the diagnostic criteria of PAH. It canbe caused by many heart, lung and pulmonary vascular disease,at the same time, it is theperformance of a lot of diseases’ progress to a certain stage, pulmonary hypertensionalso can serve as a kind of disease which could be exist independently. Main shows thatthe increased pulmonary arterial pressure and pulmonary ascular resistance, thepathoPAHysiological basis is mainly because pulmonary arterial remodeling whichcauses pulmonary circulation hemodynamic changes, gradually appeared right heartfailure and even death. Therefore, early intervention of pulmonary vascular remodelingis the key of the treatment of PAH, with the development research of stem cell therapyfor PAH research at home and abroad, on the animal experiment in stem cells researchshows that the early treatment of PAH’s function is certain. The experimental studyconfirmed the related mechanism of the stem cell therapy to PAH, and further improvethe treatment ways to make stem cell therapy PAH more safety and reliable.Objective To discuss the effect and related therapeutic mechanism of bone marrowmesenchymal stem cells (MSCs) transp1antation on the animal model of early acutedamage to pulmonary arterial hypertension (PAH) and observe the changes of vessels which transfordmed with MSCs on the animal model for2weeks.Methods MSCs were isolated，cultured from bone marrow of SD rats，and stained withRFP-Adenovirus． The rats were randomly divided into four groups: the blank controlgroup with normal saline(CONTROL group)，the non-treatment group (PAH group),theveinal treatment group(VMSCs group) and tracheal treatment group(TMSCs group).ThePAH model was induced by subcutaneous injection of MCT in VMSCs、TMSCs andPAH groups，the rats of the control group were injected with0.9%normal saline insteadof MCT. One week after MCT administration，MSCs were injected through the raninevein or tracheal into rats in the VMSCs and TMSCs groups. At the same time，rats inPAH and control groups were injected with the same amount of low-glucose DMEM（L-DMEM）．Three weeks after the injection of MCT，test the pulmonary arterypressure and the expression of Smad2and its active form，observe the thickness ofvascular wall. Abserve the fluorescence’s distribution in the lung tissue in TMSCsgroup and VMSCs group in10days and21days after the injection of MCT.Results When the SD rats were injected with the MCT for21days, PAH group’s SPAP,MPAP is significantly higher than these of Con group (P <0.05), these in VMSCs andTMSCs groups declined obviously compared with PAH group(P <0.05), but higher thanthses in the Con group (P <0.05). The thickness of vessel wall in PAH group are quitethicker than that of Con group (P <0.05), VMSCs and TMSCs groups vessel wallthickness are thinner than these in PAH group(P <0.05). The level of Smad2in PAHgroup, TMSCs group, VMSCs group are with no significant differences, but slightlyhigher than these in Con group; the level of PAHosPAHorylation Smad2in PAH groupis higher than VMSCs group, TMSCs group,higher than Con group. VMSCs andTMSCs groups in SPAP, MPAP, vessel wall thickness, Smad2and PAHosPAHorylationSmad2have no statistically different. Conlusions MSCs reduce the pressure of the vessels and the function of reconstruction,which may be related to the reduction of the expression of Smad2and Smad2PAHosPAHorylation which is related to vascular remodeling factors TGF-β，reverse theremodeling effect of pulmonary vascular, MSCs become a treatment method of the earlyinflammatory damage of pulmonary hypertension, at the same time,the trachealinjection could be a new effective approach.