Protective Effects Of PQTS On Ventricular Remodeling In Rats With Pressure Overloaded Hypertrophic Myocardium

Ventricular remodeling refers to changes in ventricular weight, size and shape, thatorigined in myocardial injury, pressure overload, volume overload and other changes. Theinitial purpose of these structural changes is to maintain effective cardiac function, but it isharmful long time, and ultimately led to heart failure. Therefore, ventricular remodeling isthe cause of the underlying causes of ventricular dysfunction and heart failure, throughoutthe most development process of cardiovascular disease, and impact on the patient’s cardiacfunction and prognosis, that is an independent risk factor for cardiovascular diseasemortality. It is the main cause that high ventricular wall tension induced by Abnormalhemodynamics and a variety of cytokines secretion abnormalities which triggeredventricular remodeling. At present, angiotensin converting enzyme inhibitors, angiotensin IIreceptor antagonists, calcium antagonists, beta-receptor blockers and nitrates are the maindrug improving ventricular remodeling.The target of these chemicals are Single, whichcould not inhibit complex ventricular remodeling completely, and they have toxicity andexpensive price that are not suitable for long-term administration.It is Chinese medicinecharacteristics that multi-target synergy, and inexpensive drug with fewer side effects, whichis an ideal way for the development of inhibition of ventricular remodeling drugs.The root of Araliaceae Panax Species American ginseng has always been used asmedicine, while its stems and leaves were mostly abandoned mountains.The chemical composition analysis showed: American ginseng saponin content in the leaves（9.05¹0.45%） was significantly higher than the roots of （3.89⁶.49%）.American ginseng total saponins contain the20s-protopanaxadiol group saponins and20s-Protopanaxadiol PTS.PQDS has been developed with independent intellectual propertyrights of traditional Chinese medicine injection, so remainder of PQTS that yield up to51.2%are urgent to the comprehensive utilization, turning waste into treasure.It has benn reported that PQTS has the protective effect on acute myocardial infarctionand myocardial ischemia reperfusion injury in the literature.In this paper, through leftventricular remodeling model that the ligation of the abdominal aortic pressure overload, wefurther observed the preventive effect of PQTS on experimental ventricular remodeling inlong-term administration.1experimental methods1.1Pressure overload left ventricular remodeling model in rat Pressure overload left ventricular remodeling model was prepared by abdominal coarctationof the aorta.Routine disinfection of the abdominal skin,30mg/kg intraperitoneal injection of3%sodium pentobarbital anesthesia, hair removal, taking the upper abdominal midline incisionto open the abdominal cavity, separating the left renal artery beginning part of the lastsegment of the abdominal aorta about10mm, a diameterabout0.6mm smooth needlesparallel in this section of the abdominal aorta, ligating abdominal aorta together with theneedle with a4.0silk, quickly removing the needles, which can be caused by abdominalaortic stenosis （65±7%stenosis）, abdominalinjection of penicillin200,000u, closing theabdominal cavity, conventional anti-inflammatory7d. The sham operation group was thesame as the other treatments without ligation of the abdominal aorta.1.2Experimental grouping and administrationSixty postoperative survival rats were randomly divided into six groups, each group of10, grouped as follows:（1） Sham group: intraperitoneal injection of saline10mL/kg/d;（2）reconstruction model group: intraperitoneal injection of saline10mL/kg/d;（3） positive druggroup: intragastric captopril tablets100mg/kg/d;（4） the PQTS low-dose group:intraperitoneal injection PQTS12.5mg/kg/d;（5） PQTS middle dose group: intraperitonealinjection of PQTS25mg/kg/d;（6）PQTS high dose group: intraperitoneal injection of PQTS50mg/kg/d. Administered once a day in each group, a total of six weeks. The gavagecapacity are10mL/kg.1.3ObservationsRat killing the night before, the animal fasting but water, the morning, killing10rats ineach group,3%sodium pentobarbital30mg/kg intraperitoneal injection of anesthesia,fixed to separate the right common carotid artery, the internal diameter for1mm plasticintubation into the left ventricle, and connect with the RM-6000multi-channel polygraph,left ventricular systolic pressure（LVSP），the left ventricular end diastolic pressure （LVEDP）,the maximum left ventricular presure rising and dropping rates （±dp/dtmax）,systolic bloodpressure （SBP）,diastolic blood pressure （DBP） andheart rate （HR） were measured.the serum from abdominal aorta was measured for MDA content and SOD activity measuredby kit method;the plasma added in MEDTA Na2and sulfuric acid,0.3M dimercapto propanolanticoagulant was measured for the content of Ang Ⅱ; the plasma added in EDTA Na2anticoagulant was measured for the content of6-Keto-PGF1α in （on behalf of PGI₂） and TXB2（on behalf of TXA₂）; the plasma added in EDTA Na2and aprotinin anticoagulantwas measured for the content of ET.Removing the heart, cutting the left and right atrium along the coronary groove, washingwith saline blood, sucking, the weight of the ventricle was calculated the heart coefficient（ventricular weight/body weight×100）Cutting about2mm myocardial tissue, immersed in4%formaldehyde to be fixed, paraffinembedded, preparing the HE staining of myocardial tissue sections, then the pathologicalchanges of myocardial tissue was observed under the optical microscope.1.4Statistical AnalysisUsing SPSS11.5software package for processing, each set of data expressed as mean±standard deviation （x±s）, Mean was compared using single factor analysis of variancebetween the two groups.2experimental results2.1Body weight, ventricular weight and heart coefficientCompared with the sham group, the rats body weight decreased significantly （P <0.05）,ventricular weight and heart coefficient increased significantly （P <0.01）in reconstructionmodel group. Compared with reconstruction model group, PQTS25,50mg/kgsignificantly reduced ventricular weight and heart coefficient （P <0.05or P <0.01）, and itsrole was considerable of drug captopril. PQTS12.5mg/kg had no significant effect on bodyweight, ventricular weight and cardiac factors in ventricular remodeling rats.2.2HE staining of myocardial tissueLight microscopy showed that:①Sham operation group, myocardial fibers arranged in regular, the nucleus elongatedoval, located in the center of the muscle fibers.Myocardial cells did not atrophy orhypertrophy, no addicted eosin stain and necrosis. no obvious edema and hyperplasia ofconnective tissue, no the occurrence of ventricular remodeling.②Model group,myocardialfibers disorganized, and thickening, myocardial interstitial edema,more connective tissueproliferation and a small amount of inflammatory cell infiltration can be seen, the occurrenceof significant ventricular remodeling;③Captopril group, the myocardial fibers arranged inregular, no obvious myocardial fiber thickening in myocardial interstitium, no edema, asmall amount of connective tissue proliferation and inflammatory cell infiltration, theoccurrence of mild ventricular remodeling;④High dose group PQTS,myocardial fibersarranged in neat, no significant thickening and a very small amount of connective tissue proliferation and inflammatory cells infiltration s in myocardial interstitium, mild ventricularreconstruction;⑤Middle dose group PQTS, myocardial fibers arranged irregularly, mildthickening, mild edema in myocardial interstitium, a small amount of connective tissueproliferation and inflammatory cells infiltration, mild ventricular reconstruction;⑥PQTSlow dose group PQTS, myocardial fibers arranged in disorder, thickening, edema inmyocardial interstitium, visible connective tissue proliferation and inflammatory cellsinfiltration, the occurrence of ventricular remodeling.2.3Hemodynamic change in ratsCompared with sham group, SBP, DBP, MAP, LVSP and±dp/dtmax were decreasedsignificantly, HR and LVDEP were increased significantly （P <0.01or P <0.001） inreconstruction model group. Compared with reconstruction model group, SBP and DBP,MAP, LVSP and±dp/dt max were increased, HR and LVDEP were decreased （P <0.05or P<0.01） in PQTS25,50mg/kg group, its role was considerable of drug captopril.There wasno significant effect on these parameters of ventricular remodeling in PQTS12.5mg/kggroup.2.4Change of serum MDA, SOD and plasma AngII, ET in ratCompared with the sham group,the content of serum MDA and plasma of AngII, the ETwas increased significantly, serum levels of SOD activity was decreased significantly （P<0.05or P <0.01） in reconstruction model group. Compared with reconstruction modelgroup, the content of serum MDA and plasma of AngII, ET content was decreased, serumlevels of SOD activity was elevated （P <0.05or P <0.01） in PQTS25,50mg/kg group, itsrole was considerable of drug captopril. PQTS12.5mg/kg had no significant effect on serumMDA content and SOD activity. There was no significant effect on these parameters ofventricular remodeling in PQTS12.5mg/kg group.2.5Change of plasma PGI₂and TXA₂in ratCompared with the sham group,the content of plasma TXA₂was increased significantly, the content of plasma PGI₂content and PGI₂/TXA₂ratio was decreased significantly （P <0.05or P <0.01） inreconstruction model group. Compared with reconstruction model group, the content ofplasma TXA₂was decreased significantly, the content of plasma PGI₂content andPGI₂/TXA₂ratio was increased significantly （P <0.05or P <0.01） in PQTS25,50mg/kggroup, its role was considerable of drug captopril. PGI₂/TXA₂ratio was decreasedsignificantly, while there was no significant effect on these parameters of ventricular remodeling in PQTS12.5mg/kg group.3Experimental conclusions3.1Ventricular weight and heart coefficient were decreased significantly, myocardial tissuereconstruction pathological changes were inhibited, which suggested that PQTS hasprotective effect on left ventricular remodeling induced by pressure overload in rats3.2SBP and DBP, MAP, LVSP and±dp/dt max were increased, HR and LVDEP weredecreased in PQTS group, which suggested that PQTS could improve systolic and diastolicfunction in ventricular remodeling rats3.3The content of serum MDA was decreased, serum levels of SOD activity was elevatedin PQTS group, which suggested it was the role of anti-ventricular remodeling of PQTS thatreducing the lipid oxidation products accumulation, enhancing the body ability of freeradical scavenging;3.4The content of plasma TXA₂was decreased significantly, the content of plasma PGI₂content and PGI₂/TXA₂ratio was increased significantly in PQTS group, which suggestedthat its anti-ventricular remodeling may related to correct the imbalance of PGI₂/TXA₂3.5The content of plasma of AngII, ET content was decreased in PQTS group, it was ofgreat significance to improve coronary blood flow in ventricular remodeling.In conclusion, the anti-Ventricular Remodeling effect of PQTS was result of multi-channelintegrated onset.