| Backgrounds Coronary atherosclerotic heart disease is the leading cause of death at present.Almost acute myocardial infarction(AMI)result from coronary atherosclerosis with superimposed coronary thrombosis.The necrotic myocardial cells were replaced by the fibrocyte,leading the reversible remodel of myocardium and the malfunction of heart.It is well known that stem cell have reinstated the concept of cellular transplantation to replace impaired cells, the transplantation of bone marrow mesenchymal stem cells(MSCs)have showed a great promise to recover heart function.The cell-base therapy, however,is still at its period of infancy,and its safety is always major concern in involving stem cells.Whether transplanting the MSCs have the potential adverse of proarrhythmia,which is still unknown.Objective To investigate whether MSCs transplantation can improve the content of Cx43,Cx45,and the role of Cx43/Cx45 on arrhythmia.Methods 60 Wistar rats were randomly divided into 4 groups:Normal control group,Sham operation group,AMI+NS group and the AMI+MSCs group. Experimental animal model of AMI was established by ligating the left anterior descending(LAD).Exogenous MSCs were isolated from bone marrow and cultured,expanded and labeled with DAPI.A week after AMI,2×10~6/100UL MSCs(MSCs group)were transplanted by injecting into the border and center area of infarction.The experimental animal was killed quickly after finishing the electrophysiology test.The expression of Cx43,Cx45 were detected by western blotting(WB)Results(1)The rate of effective ligation and surviving 12 weeks was 63%(19/30).The sensitivity and specificity of ST-segment or J elevating (＞0.2mv)for diagnosing AMI were 88.2%(15/17)and 100%,respectively. Pathologic Q wave or QS wave was seen in the experimental model of AMI.(2) Exogenous MSCs grew in adherence conditions in fusiform,without differention even after generation 5-6.(3)The MSCs tagged by DAPI were seen in the MI+MSCs roup during 2,4,8,12 weeks,but the fluorescence is becoming decreasing day by day.(4)The content of Cx43 in Normal control group was (0.78±0.10),(0.70±0.08)in sham operation group,the normal area,border zone and the middle of infarction in MI+NS group were (0.68±0.09,0.35±0.05,0.24±0.01),respectively,and (0.69±0.04,0.46±0.03,0.29±0.02)in the similar area of MI+MSCs group, respectively.The content of Cx43 in the border zone of AMI+MSCs group was significantly higher than in the same area of AMI+NS group(P＜0.05).(5)The content of Cx45 in Normal group was(0.38±0.08),(0.36±0.06)in Sham operation,(0.34±0.08,0.30±0.05,0.27±0.06)in the normal area,border zone and middle of infarction of MI+NS group,(0.35±0.07,0.31±0.09, 0.26±0.04)in the similar area of of MI+MSCs group.There is no significant difference in the content of Cx45 between the MI+NS group and the MI+MSCs group in the border zone(P＞0.05).(6)One animal model was induced to ventricular tachycardia in normal group(1/15,6%),1 with ventricular fibrillation in sham operation group(1/15,6%),4 with ventricular fibrillation,2 with polymorphic ventricular tachycardia,2 with ventricular tachycardia in AMI+NS group(8/15,53%),1 with polymorphic ventricular tachycardia,1with ventricular tachycardia in AMI+MSCs group(2/15,13%)Conclusions(1)It is a convenient,easy,and repeatable way by ligatting LAD to establish experimental model of AMI.(2)It is feasible and effective for injection of mesenchymal stem cells transplantation in the rats with AMI.(3) The expression of Cx43 decreases in the border zone of infarction in the rats with AMI,the content of Cx43 in the AMI+MSCs group is improved by transplanting the MSCs,it may be expected to reduce the increased risk of ventricular arrhythmia caused by AMI. |
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