Effects Of Recombinant Adenovirus-hepatocyte Growth Factor Therapy On Left Ventricle Myocardial Fibrosis And Heart Function In Spontaneously Hypertensive Rats

Objectives: To explore the effects on myocardial fibrosis and heart function inspontaneously hypertensive rats （SHR） after locally injected withadenovirus-hepatocyte gene fator（Ad-HGF） at left free ventricular wall.Methods: The experiment was carried out from March2011to September2011at the animal surgery center and the central laboratory of the First Hospital Affiliatedto Anhui Medical University.（1） Sixty14week-old SHR,served as myocardialfibrosis models,were randomly divided into four groups:Positive control group（Pgroup）,Adenovirs group（A group,A group,null-Ad5,0.1ml）,Low-dose group（Lgroup,1x10⁹Pfu/ml Ad5-HGF,0.1ml）,High-dose group（H group,5x10⁹Pfu/mlAd5-HGF,0.1ml）.Normal control group（N group） consisted of twenty four Kyoto（WKY） rats.（2） After thoracotomy,we respectively injected0.1ml null-Ad5to Agroup,1x10⁹Pfu/ml Ad5-HGF to L group and5x10⁹Pfu/ml Ad5-HGF to H group atfive points of the left ventricular wall.They were fed after transfection（altogether13survived in A group,14in L group and12in H group）.Six of each group wererandomly sacricfied at4^th,8th week.（3） Tail artery pressure and left ventricularpressure of each one were measured.（4） Plasma and cardiac HGF concentration wasmeasured with ELISA assay.（5） Cardiac AngⅡ level was detected withradioimmunity assay.（6） Left ventricular mass index was detected.（7） Collagenvolume fraction （CVF） was analyzed by Masson’s method.（8） Cardiac TGF-β₁andCollagen I were detected with Immunohistochemical method and image analysissystem.（9） Cardiac HGF,AngⅡ,TGF-β₁and Collagen I protein content wereassessed by Western blot. Results:（1） Compared A group with P group,there was no statistically differece（P>0.05） inthe indexes of left ventricular myocardial fibrosis and heart function.（2） At4th week,Left ventricular mass index,the CVF,the cardiac AngⅡ,TGF-β₁andCollagen I level of L-group SHR all decreased compared with P group,while cardiacHGF increased（P<0.05）,and no statistically differece in plasma HGF （P>0.05）;Compared L group with P group, no significant difference （P>0.05） occurredon plasma and cardiac HGF levels at8th week,while left ventricular mass index,theCVF,the cardiac AngⅡ,TGF-β₁and Collagen I level decreased （P<0.05）.（3） Compared H group with P group,the SBP,-dp/dtmax,left ventricular mass indexes,the CVF,the cardiac AngⅡ,TGF-β₁and Collagen I level in H group decreased at4thweek,while cardiac HGF increased （P<0.05）,and no significant difference （P>0.05）on plasma HGF level;At8th week,SBP,LVESP,-dp/dtmax,HR,left ventricular massindexes,CVF,cardiac AngⅡ,TGF-β₁and Collagen I level in H group decreased and+dp/dtmax increased compared with P group,while no significant difference （P>0.05）on plasma and cardiac HGF level.（4） Compared H group with L group,the SBP,-dp/dtmax,left ventricular mass index,the CVF,the cardiac AngⅡ,TGF-β₁and Collagen I level in H group decreaed andcardiac HGF increased（P<0.05） at4^th week,and no significant difference（P>0.05） onplasma HGF;At8th week,the SBP,LVESP and,-dp/dtmax,HR,left ventricular massindex,the CVF,cardiac AngⅡ,TGF-β₁and Collagen I level in H group decreasedand+dp/dt max increased（P<0.05）,and no significant difference（P>0.05） onplasma and cardiac HGF level.Conclusion:（1） Ad-HGF therapy can inhibit the left ventricular myocardial fibrosis and improvecardiac function in SHR.High-dose of Ad-HGF is more likely to resist myocardialfibrosis than lower dose of Ad-HGF.（2） The function of resisting myocardial fibrosis may be related to inhibition of AngⅡand TGF-β₁expression,and reduction of Collagen I.