| Objective: This study takes the rats induced by adriamycin cardiomyopathyas the research object, to explore whether exogenous hydrogen sulfide canreduce myocardial fibrosis by regulating the expression of TGF-β1and itsdownstream pathway of MMP-2and MMP-9. Provide a new theory basis forinhibition of myocardial fibrosis.Methods: In this study,40maleSprague-Dawley (SD) rats were randomly divided into four groups:①doxorubicin (adriamyein, ADR, doxorubicin) group (n=12), intraperitonealinjection of ADR2.5mg/kg, one times/week;②ADR+NaHS group (n=12),intraperitoneal injection of ADR2.5mg/kg, one times/week, and NaHS14μmoL/kg/day (after injection ADR1h).③NaHS group (n=8), intraperitonealinjection of NaHS14μmoL/kg/day.④control group (n=8), intraperitonealinjection of the0.9%sodium chloride solution1ml/kg,onetimes/week.continuous medication for10weeks. before and after the intervention,measurements the rats cardiac cavity diameter with cardiac echocardiography:included left ventricular end-diastolic diameter (LVEDD), left ventricularend-systolic inside diameter (LVESD), interventricular septal thickness (IVS)and left ventricular posterior wall (LVPW), Left ventricular ejectionfraction(LVEF) and Left ventricular fraction-Shortening(LVFS) were calculatedaccording to the formula Teichholtz correction. The rats were sacrificed after the intervention, and myocardial Specimens were taken for studied following:①Take the heart tissue of rats made the paraffin embedding sectioning and HEstaining, and observed the pathologic changes of the myocardial tissue of ratsby the microscope.②Detecting hydrogen sulfide (H2S), transforming growthfactor beta1(TGF-β1), Matrix metalloproteinases2(MMP-2) and Matrixmetalloproteinase9(MMP-9), and the collagen type I and type III by enzymelinked immunosorbent (ELISA) method in the myocardial tissue of rats③Detecting the expression of TGF-β1mRNA in the myocardial tissue of rats bythe Real-time fluorescent quantitative PCR (real-time PCR, policy RQ-PCR)technology.Results:1.Case of rats survival: the survival rate of four groups ofrats respectively: control group88%,ADR group50%, ADR+NaHS group42%,NaHS group75%.2.Echocardiography examination: The LVEDD,LVESD inADR and ADR+NaHS groups comparison with before and after the interventionwere statistically difference (P<0.05); After the intervention,the LVEDD,LVESD in ADR+NaHS group compared with the ADR group were statisticallyreduced(P<0.05)； the LVEF, LVFS in ADR+NaHS group compared with theADR group were statistically improvement (P<0.05). the LVPW and IVS wereno statistical difference in each group rats (P>0.05).3. In the ADR group,myocardial cells were arranged in disorder, and part of them appeareddegeneration and necrosis phenomena such as fiber fracture and dissolved of thecytoplasm. In the ADR+NaHS group myocardial cells were arranged in neatrows，there is no degeneration and necrosis phenomena, only part of the them appeared vacuoles degeneration,The NaHS group similar to the controlgroup,the myocardial cell was no changed significantly.4. ELISA results:①theexpression of collagen type I and III in the myocardial tissue of the ADR andADR+NaHS groups compared with the control group were increasedsignificantly (P<0.05)，and in the ADR+NaHS group compared with the ADRgroup were reduced significantly (P<0.05).②the expression of H2S in themyocardial tissue of the ADR group compared with the other three groupsdecreased significantly (P<0.05).③the expression of TGF-β1in themyocardial tissue of the ADR and ADR+NaHS groups compared with thecontrol group were increased significantly (P<0.05)， and in the ADR+NaHSgroup compared with the ADR group were reduced significantly (P<0.05),butin NaHS group compared with the control group also reduced significantly(P<0.05).④the expression of MMP-2and MMP-9in the myocardial tissue ofthe ADR and ADR+NaHS groups compared with the control group wereincreased significantly (P<0.05)，and in the ADR+NaHS group compared withthe ADR group were reduced significantly (P<0.05), while in the NaHS groupcompared with control group no significant change (P>0.05).5. RQ-PCR results:the expression of TGF-β1mRNA in the myocardial tissue of the ADR andADR+NaHS groups compared with the control group were increasedsignificantly (P<0.05)，and in the ADR+NaHS group compared with the ADRgroup were reduced significantly (P<0.05),but in the NaHS group comparedwith the control group also reduced significantly (P<0.05). Conclusion: effects of exogenous hydrogen sulfide can reduce myocardial fibrosis and improvecardiac function in rats by reducing the expression of TGF-β1and itsdownstream pathway of MMP-2and MMP-9. |
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