| Objective: Establish the model of acute myocardial infarction (AMI), andgranulocyte colony-stimulating factor (G-CSF) in the intervention, observation of G-CSFon cardiac remodeling and cardiac function improved, and explore the impact of differentdelivery methodsthe extent and possible mechanisms of action, and thus provide atheoretical basis for clinical trials of G-CSF treatment of AMI.Methods: Left anterior descending coronary artery ligation method to establishanimal models of myocardial infarction. Experimental animals were divided into fourgroups: sham group(A group), AMI group(B group), AMI+G-CSF low-dose progressiveincreased group(C group), AMI+G-CSF high-dose group(D group); Take infarctionwithin12hours after intraperitoneal injection of drug delivery method (group A only doopen heart treatment, Group B with normal saline instead of G-CSF, and Usage withGroup C, group C on the1st5ug/kg daily increments5ug/kg, for7days, group D20ug/kg/d for7days, the two intervention groups for each rat the total dose are140ug/kg)；Modeling after10days, take heart tissue samples by Western-blot method ofdetection total Akt, phospho-Akt, Bcl-2and Bax protein expression; Modeling after28days have inspection hemodynamic evaluation of cardiac function, hearts weresubsequently collected, HE staining, Masson trichrome, Ⅷ factor staining，myocardialinfarction and survival of myocardial tissue surrounding the infarct area and scarformation, collagen deposition, angiogenesis situation.Results: ECG show that myocardial dead animal model was successfully created;Western-blot results: among all groups the amount of total Akt protein expression was no significant difference（p>0.05）. Compared with B group, the phospho-Akt proteinexpression of C group and D group were significantly increased (p <0.01C group vs Bgroup; p <0.05D group vs B group). phospho-Akt protein expression of C group wasmore significantly than D group（p<0.05）; obtained in the detection of Bcl-2and Baxprotein expression results, compared with A group, inhibition of apoptosis protein Bcl-2expression in the B group was significantly reduced（p<0.05）, while promoting apoptosisprotein Bax expression was significantly increased（p<0.05）. Compared with B group,the Bcl-2protein expression of C group and D group was significantly increased (p<0.01C group vs B group; p <0.05D group vs B group), and Bax protein expression wassignificantly reduced (p<0.01C group vs B group; p <0.05D group vs B group). TheBcl-2and the Bax protein expression of C group is more significant than D group（p<0.05）. Hemodynamic analysis: all of interventional groups have reduced theLVEDP（p<0.05）, LVSP and±dP/dtmax were increased（p<0.05）, cardiac function areimproved; C group in heart function was more significantly improved than D group（p<0.05）. HE staining showed that: compared with B group，C group and D groupincreased residual myocardial cells, their fibrous scar tissue were reduced, the formereffect is more obvious.Masson staining：compared with A group, the formation of fibrousscar tissue in B group was most obvious than any others, C group and D group reducedthe formation of fibrous scar；the former fibrous scar was less. Masson stain photosquantitative results: Compared with group A, group B infarct size and collagen volumefraction increased significantly (40±5%,8.52±0.54%, p <0.01); Compared with groupB, C and Dgroup infarct area and collagen volume fraction was significantly reduced(group C31±3%,5.95±0.38%, p <0.05; D, groups of33±4%,6.68±0.41%, p-<0.05),group C and D groups without significant withdifference (p>0.05).Ⅷ factor stainingcapillary density results showed that: G-CSF in the intervention group infarct area andinfarct peripheral regions of angiogenesis were significantly higher than B group（p<0.05）. Number of blood vessels between the close of C group and D group（p>0.05）. Conclusion: G-CSF for the myocardial infarction zone and the surrounding areas ofmyocardial infarction has a protective effect, using the low-dose progressive increase isbetter than the high-dose, the former can be more obvious inhibition of cardiomyocyteapoptosis, reduced collagen deposition, and promote angiogenesis to achieve to preventpost-infarction left ventricular remodeling, improve cardiac function. |
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