Effect Of Apelin-13on TGF-β₁/Smads Pathway In Rats Myocardial Fibrosis Induced By Pressure Overloaded And Its Mechanism

ObjectiveTo study the effect of Apelin-13on myocardial fibrosis in rats Induced bypressure overload and to clarify its mechanism.Methods40SD rats were divided into sham-operation group,model group,apelin-13group,and SB431542group randomly,10in each group. Rats in thesham-operation group were only separated their abdomens aorta. Threegroups rats else were made into the model of myocardial fibrosis successfully.Three days after modeling100μg/(kg·d)apelin-13injection was administered torats in the apelin-13group，100μg/(kg·d)SB431542injection to rats in theSB431542group by peritoneal injection，At the same time,sham-operationgroup and the model group were injected normal saline.4weeks later, theircardiac index and left ventricular mass index (LVMI) were estimated.Morphology of collagen in myocardial tissue was observed with Massonstaining, collagen volume fraction (CVF) in left ventricular interstitial tissue wasmeasured by image analysis, The serum transforming growth factorβ1(TGF-β1) expression was detected using ELISA and expressions of TGF-β1protein, the collagenⅠ、Ⅲ were detected by Western blot. The Smad3andSmad7mRNA in myocardial tissue expressions were detected using Real-timePCR.Results1. Comparison of H/B、LVMI:Compared with Sham group,the H/B, LVMI were significantly higher (P <0.05)in AOB group; compared with AOB group,the body weight increased significantly (P<0.05), H/B, LVMI decreasedsignificantly (P<0.05) in Apelin-13group and SB431542group, especially inApelin-13group.2. Comparison of hemodynamic parameters:compared with sham group,LVSP,+dp/dtmax and-dp/dtmax were significantly decreased (P<0.05),LVEDP was significantly increased (P<0.05) in AOB group; compared withAOB group,LVSP,+dp/dtmax and-dp/dtmax were significantly higher (P<0.05), LVEDP was significantly decreased (P<0.05)in Apelin-13andSB431542group.3. Collagen content comparison by Masson staining: myocardial cellswere stained red and collagen fibers were blue observed by Opticalmicroscope, We found that myocardial tissue arranged regularly,and there waslittle collagen fibers around artery in the Sham group rats. Content ofmyocardial collagen fiber were increased and the myocardial tissue arrangeddisorderly in other groups else. Compared with AOB group,the content ofmyocardial collagen fiber were decreased obviously in Apelin-13group andSB431542group which Apelin-13group improved significantly.Semi-quantitative analysis showed that CVF in AOB group was significantlyhigher than the sham group (P <0.05);The CVF of Apelin-13and SB431542group were significantly lower than AOB group (P<0.05).4. Comparison of serum TGF-β1levels in different groups:Compared withthe Sham group, the serum TGF-β1level was significantly increased in AOBgroup(P <0.05);Compared with the AOB group, the serum TGF-β1levels ofApelin-13group and SB431542were significantly decreased (P <0.05).5. Expression of TGF-β1, Ⅰ and Ⅲ collagen in different groups:Compared with the sham group,the expression levels of TGF-β1、collagen typeⅠ and Ⅲ were significantly increased in AOB group (P<0.05); Compared withthe AOB group, the expression levels of TGF-β1、collagen type Ⅰ andⅢwere significantly lower in Apelin-13and SB431542group (P<0.05), which changed more significantly in Apelin-13group.6. Expression levels of Smads3and Smads7mRNA:Compared with thesham group,Smad3mRNA expression level was significantly increased inAOB group (P<0.05), whereas the expression of Smad7was significantlylower (P <0.05);Compared with the AOB group, Smad3mRNA expressiondecreased and Smad7mRNA expression increased significantly in Apelin-13group (P <0.05); Smad3mRNA expression was significantly lower inSB431542group(P<0.05), but the expression of Smad7mRNA was nosignificant difference, Compared with Apelin-13group, the expression ofSmad3mRNA was no significant difference in SB431542.ConclusionPressure overload can lead to myocardial fibrosis in rats;Apelin-13canpartially relieve pressure overload-induced cardiac fibrosis in rats;Apelin-13relieve myocardial fibrosis induced by pressure overload in rats through partialinhibiting TGFβ1-Smads signal pathway．...