Study Of The Role Of Inflammatory Cells In Myocardial Fibrosis Of Spontaneously Hypertensive Rats And The Effects Of Benazepril On Them

Objective To investigate cytological mechanisms of myocardial fibrosis in spontaneouslyhypertensive rats. To explore the role of inflammatory cells in the progression of fibrosisand study the effects and possible mechanisms of benazepril.Methods 12-week-old male SHRs were divided into hypertension group(SHR,n=10),benazepril treatment groups(BenL,BenH subgroup;Rats respectively receivedbenazepril 1.7,17mg?kg-1?d-1 intragastric administration ;n all=10),and age and sexmatched Wistar Kyoto rats were set as control group(WKY,n=10).After 18 weeks,intervention,all rats were sacrificed after hemodynamics surveyed ; Morphologicalcharacteristics were measured with HE, Sirus-red. Left ventricular mass (LVM) , leftventricular mass index (LVMI) were measured and calculated;Content of left ventricularcollagen and cardiomyocytes area(CA)were assessed with compute-assisted imageanalysis system. Immunohistochemistry staining labled cardiac fibroblasts ,macrophages,vascular endothelial cells ,myofibroblasts and fibronectin(FN) andlaminin(LN) ,transforming growth factor-β1 (TGF-β1 )with correspondingantibodies;The transcriptional level of TGF-β1 and interleukin-6 (IL-6)wereevaluated by reverse transcription polymerase chain reaction(RT-PCR).Results 1. Mean arterial pressure(MAP),left ventricular systolic pressure( LVSP),leftventricular end-diastolic pressure( LVEDP)of SHR group were much higher thanWKY group (P all <0.05); MAP,LVSP,LVEDP of BenH group were much lowerthan SHR group(156.43±19.92 vs 195.23±15.82mmHg;175.12±11.92 vs 207.60±17.73mmHg;6.33±1.15 vs 8.01±1.50mmHg;P all<0.05);However,the same effectswere scarcely found in BenL group.Left ventricular hypertrophy and myocardial fibrosis were observed in SHR group.collagen volume fraction (CVF),perivascular circumferential collagen area (PVCA)were decreased in BenL and BenH group ;However ,only BenH group,it's LVM,LVMI, CA of BenH group were lower than those in SHR group (P all<0.05) . However,the same effects were scarcely found in BenL group.3. The number of Vimentin—positive fibroblasts and EDI—positive macrophages inleft ventricle of SHR group were strikingly increased when compared with SHR group (173+42 cells/mm2 vs 95 + 30 cells/mm2; 19 + 8 cells/mm2 vs 9 + 7 cells/mm2; Pall<0. 01); The amount of fibroblasts and macrophages of BenL and BenH group weremuch lower than those in SHR group (P all<0.05).4. The integrated optical density (IOD) ofFN, LN in the left ventricle of SHRgroupwere remarkably higher than those in WKY group (1637.89+174.28 vs 661.36 +122.31; 2552.74 + 232.17 vs 939.79+166.17; PalKO.01); The positive area /thetotalarea of FN and LN in SHR group were significantly increased when compared withSHRgroup (0.15%+ 0.03% vs 0.07% + 0.02%; 0.16%+ 0.02% vs 0.09%+0.02%; Pall<0.01); FN were decreased by 20%, 46% and LN were reduced by 19%, 31 %in BenLand BenH group respectively when compared with SHR group.5. The average optical of TGF—Pi in the left ventricle of SHR was notably higher thanthat in WKY group (274.05 + 16.46 vs 188.60+19.41, P <0.01) . The amount of theexpression of TGF—Pi were decreased in BenL and BenH group when compared withSHR group (P all <0.05). The transcriptional level of TGF—p, and IL—6 in SHR groupwere much higher than those in WKY group (P all <0.01) . The mRNA level of TGF-Pi and IL—6 of BenL and BenH group were lower than those in SHR group (P all<0.05) .