|
Objective: To investigate the effects of clopidogrel on mesenchymal stem cells which were transplanted to Sprague Dawley rats after myocardial infarction and the cardiac function of them. And to study preliminarily the mechanism of the action.Methods: According to the different adherent characteristic of cells, isolate and culture MSCs from the tibia and femur of aged 8 weeks SD rats. And the passage 3th cells were transplanted. Ligate a branch of coronary artery by thoracotomy to finish 40 myocardial infarctional SD rats weighing 200g. They were randomly divided into 4 groups: Group A was the blank group, they were had placebo and tranplanted normal saline via the tail vein. Group B was the MSCs group, they were had placebo and tranplanted MSCs. Group C was the clopidogrel group, they were had clopidogrel and tranplanted normal saline. Group D was the experimental group, they were had clopidogrel and tranplanted MSCs. They were had 3mg/kg of placebo or clopidogrel every day since the 7th day after ligated coronary atery, and tranplanted 0.5ml of normal saline or 1×10~6 of MSCs (0.5ml) in the 14th day. In the 6th week, we detected left ventricular internal diameter at end-diastole, left ventricular internal diameter at end-systole, left ventricular ejection fraction by color Doppler echocardiography, measured the area of the infarctional myocardium, calculated the MSCs and the newborn capillary endothelial cells in the myocardium using immune enzyme united response. Survey the effect of exogenous cyclic adenosine monophosphate(cAMP) on the MSCs of proliferation.Results: There was no significantly diference of LVIDd level among Group A and Group C (P>0.05), Group B were less than Group A 6.45±0.34mm VS 7.28±0.12mm (P<0.05), Group D were less than Group A 5.89±0.13mm VS 7.28±0.12mm (P<0.05), Group B were larger than Group D 6.45±0.34mm VS 5.89±0.13mm (P<0.05). For LVIDs, A>C>B>D. For LVEF, A<C<B<D. For the area of infarctional myocardium accounting for left ventricular percentage, there was no significantly diference among Group A and Group C 36.21±0.80% VS 35.42±0.85% (P>0.05), Group B were less than Group A 29.64±1.52% VS 36.21±0.80% (P<0.05), Group D were less than Group A 24.52±1.61% VS 36.21±0.80% (P<0.05), Group D were less than Group B 24.52±1.61% VS 29.64±1.52% (P<0.05). Brd U positive cells weren’t found in myocardial slice at Group A and Group C, while Group B were less than Group D in every high power field 22.2±1.92 VS 32.6±3.85 (P<0.05). Through the immune enzyme united response ofⅧfactor, the newborn capillary endothelial cells of Group B in infarctional myocardium were less than Group D 25.6±7.65/mm~2 VS 38.3±9.24/mm~2 (P<0.05). The concentration of cAMP in the plasma of Group C were higher than the Group A 21.05±2.03nmol/L VS 10.57±0.89nmol/L (P<0.05). The absorbance (OD 450nm pm) of exogenous cAMP group was significantly higher than the blank group 0.69±0.03 VS 0.60±0.02 (P<0.05).Conclusion: 1, Transplating MSCs can decrease the area of infarctional myocardium of rats, and increase cardiac function. 2, Clopidogrel can strengthen the effect. 3, Clopidogrel can promote the proliferation of MSCs, through increasing the concentration of cAMP.
|