Hepatocyte Growth Factor And Valsartan Synergistically Attenuate Myocardial Fibrosis In Spontaneously Hypertensive Rats

Objective To observe the effect of both hepatocyte growth factor and valsartan onmyocardial fibrosis of Spontaneously Hypertensive Rats and investigate itsmechanism.Methods Wistar rats were as normal control (N group, n=6); spontaneouslyhypertensive rats (n=30) were randomly assigned into five groups (n=6): hypertensioncontrol(P group); sham control (sham group, at the begin of the research, delivery ofnull-Ad5,0.1ml into the left ventricle wall at five different points by direct injection andthen fed them normally for4weeks); HGF(H group, at the begin of the research,delivery of5x109Pfu/ml Ad5-HGF,0.1ml into the left ventricle wall at five differentpoints by direct injection and then fed them normally for4weeks); valsartan[V group,delivery of valsartan30mg／(kg d)by intragastric administration];both HGF andvalsartan [HV group, at the begin of research, delivery of5x109Pfu/ml Ad5-HGF,0.1mlinto the left ventricle wall at five different points by direct injection and then gavevalsartan30mg／(kg d) by intragastric administration for4weeks].Every group wastaken tail blood pressure at the start of this study and every week during administrationperiod. After4weeks treatment, the expression of HGF, TGF-β1and MMP-1in leftventricle was assessed by Enzyme-Linked Immunosorbent Assay(ELISA), myocardialCollagen Volume Fraction (CVF) was evaluated by Masson collagen staining method,CollagenⅠandα-smooth muscle actin(α-SMA) in left ventricle were observed byimmunohistochemistry and tested by Western blot analysis.Results 1. At the begin of the study, the tail mean blood pressure of N group （93.83±6.62mmHg）was significantly lower than that of P group（147.89±7.14）mmHg, shamgroup（149.62±6.99）mmHg, H group（147.52±6.69）mmHg, V group（146.24±7.82）mmHg and HV group （151.05±6.62）mmHg (P <0.05), which betweenthe last5groups had no significant difference (P>0.05).After one week of administration, the systolic blood pressure(SBP)of P and shamgroups leveled of（f202.69±3.14，201.36±1.63）mmHg which is higher than other4group（sP<0.05）; After two weeks of medication, the blood pressures of V groupand HV group dramatically decreased to（151.56±6.58，150.96±6.20）mmHg（P<0.05）. The changes of the diastolic blood pressure (DBP) in each group weresimilar to that of SBP.2. This study found that after4weeks of treatment, compared with P group:(1)The level of HGF in left ventricle was the highest in HV group (86.26±1.09ng/L)(P<0.05), which was followed by H group(83.49±1.05ng/L), Vgroup（77.32±2.20ng/L);(2)The amount of MMP-1in left ventricle increased in the groups receivedtreatment, especially in H group(3.98±0.19ng/mL) and HV group（3.86±0.11ng/mL）（P<0.05）;(3)The concentration of TGF-β1was on an opposite trend, wich was the lowestin HV group (266.11±4.16pg/L)（P<0.05）, which was followed by Hgroup(307.31±3.67pg/L), V group（303.01±3.39pg/L);(4)CVF,collagen Ⅰandα-SMA in H group,V group and HV group were allreduced, especially in HV group（P<0.05）.Conclusions1. Hepatocyte growth factor, valsartan and combination of them could, in differentextent, attenuate myocardial fibrosis in SHR. 2. Combination of Hepatocyte growth factor and valsartan can synergisticallyattenuate myocardial fibrosis in SHR, whose effect is better than each of them3. The combination may intervene more comprehensively—could suppress theexcessive expression of TGF-β1,adjust the level of MMP-1and inhibit the processthat fibroblasts transform to myofibroblasts more effectively and efficiently,wichenhance the curative effect.