The Experiment And Study Of HMGB1Delivery And MSCs Transplantation’s Effect On Cardiac Function After Acute Myocardial Infarction For Rats

Objective: Our previous research has confirmed that MSCs transplantation can promotemicrovascular generated after myocardial infarction, to improve cardiac function aftermyocardial infarction. Because of MSCs transplantation survival rate is low, myocardialinfarction area inflammation, makes a lot of transplanted cells apoptosis, and many otherproblems quickly, significantly reduce its therapeutic effect.Research shows that: HighMobility Group protein1(High Mobility Group Box1, HMGB1) can promoteangiogenesis by regulating tissue damage related factors and the expression ofinflammatory cytokines, May further stimulate proliferation and differentiation of stemcells and paracrine effect, and to participate in the organization of wound repair.This studyproposed on rat model of acute myocardial infarction, by injecting HMGB1andantagonism HMGB1expression, at the same time combining transplantation of MSCs.wewill observe if can promote the survival of stem cells, by improving the local environmentso as to better bring into play the role of stem cells to repair the myocardial.Methods:138only SD male rats, Randomly divided into six groups: Normal controlgroup (18), model control group (24), MSCs transplantation group (24), HMGB1injectiongroup (24), HMGB1injection+MSCs transplantation group (24), HMGB1BoxA injection+MSCs transplantation group (24). First by sidewall centrifugation training for high purityrat MSCs, the second step is to identify the cell phenotype. Then we make rat model ofacute myocardial infarction, In accordance with the method of making model after thesuccess of intramyocardial injections of1.0x106MSCs,100ng HMGB1peritoneal within2injections, MSCs transplantation combined HMGB1injection, MSCs transplantation andperitoneal injection of HMGB1BoxA400μg, we treat the other four groups of model. Byusing the method of echocardiography, pathology, immunohistochemical of new bloodvessels and ELISA test for concentration variation of TLR4,IL-6,NF-b,TNF-α,VEGF andHMGB1, we evaluate the results of the experiment.Results:1. Determination of cardiac function:28days after each line of echocardiography to detectLVDd, an LVDs, FS and EF value, the results show that with MSCs transplantation group, HMGB1injection group, HMGB1BoxA injection+MSCs transplantation group, HMGB1injection+MSCs transplantation group cardiac function to improve the most significant in theorder: MSCs transplantation group> HMGB1BoxA injection+MSCs transplantationgroup> HMGB1injection group> model control group (P <0.05).2. Determination of infarction area:28days after myocardial TTC staining showed thatHMGB1injection+MSCs transplantation group of infarction area of the drug interventionin other three groups significantly decreased, The rest of the group of infarction areameasurements in the order: model control group>HMGB1injection group>HMGB1BoxAinjection+MSCs transplantation group>MSCs transplantation group (P <0.05).3. Determination of myocardial infarction area of new blood vessels: HMGB1injection+MSCs transplantation group of CD31staining angiogenesis of drug intervention in otherthree groups increased significantly, The rest of the group of new blood vesselsmeasurements in the order: MSCs transplantation group>HMGB1BoxA injection+MSCstransplantation group>HMGB1injection group>model control group (P <0.05).4. TLR4, VEGF and serum HMGB1level: TLR4, serum VEGF measurements(postoperative day3) in the order: HMGB1injection+MSCs transplantation group>MSCstransplantation group>HMGB1BoxA injection+MSCs transplantation>HMGB1injection group>model control group, serum TLR4, VEGF measurement value (7days) inthe order: HMGB1injection+MSCs transplantation group>HMGB1injectiongroup>MSCs transplantation group>HMGB1BoxA injection+MSCs transplantationgroup>model control group, Serum levels of HMGB1measurements (after3days,7days)in the order: model control group>MSCs transplantation group;28days point TLR4, VEGFand HMGB1levels between groups was no statistical difference (P <0.05).5. Serum IL-6, NF-b and TNF-α evel: serum IL-6, NF-b and TNF-α value(postoperative day3) in the order: HMGB1injection group>model control group>HMGB1injection+MSCs transplantation group>MSCs transplantation group>HMGB1BoxAinjection+MSCs transplantation, Serum IL-6,NF-b and TNF-α value (7days) in theorder: model control group>HMGB1injection group>MSCs transplantationgroup>HMGB1BoxA injection+MSCs transplantation>HMGB1injection+MSCstransplantation group,28days on IL-6, NF-b and TNF-α levels between groups was nostatistical difference (P <0.05).Conclusion: HMGB1and MSCs transplantation treatment comparing single MSCstransplantation therapy for acute myocardial infarction rats Cardiac function improved, reducing myocardial infarction area, increased local new blood vessels, increased localpromote angiogenesis factor expression of infarcted myocardium and the expression ofinflammatory factor to reduce more beneficial. Antagonism HMGB1combined MSCstransplantation treatment of myocardial infarction is not correct.