The Role Of Telomerase In The Pathogenesis Of Adriamycin-induced Cardiomyopathy And The Effect And Mechanism Of Astragaloside On Cardiomyopathy Induced By Adriamycin

Objecetive: To study expression of telomere in cardiomyopathy .To study the anti-apoptosis effect and mechanism of Astragaloside on cardiotoxicity induced by Adriamycin (ADR).Methods: The SD rats were divided randomly into four groups: normal contral group(A group),ARD group(B group),ARD+ Astragaloside treatment group(C group) and Astragaloside treatment group(D group).The animal of B group and C group were given adriamycin by intraperitoneal injection at the dosage of 2.5mg/kg wt weekly. The dosage will be adjusted according to the rats weight once a week.The total is 6.The Agroup and D group were treated by normal saline.The C group and D group were raise by animal feeds containing Astragaloside.And test rats were gived by common animal feeds.Then the degree of myocardial injury.was observed with HE staining.The apoptosis of cell was detected with TUNEL method and Expression of telomerase reverse transcriptase was observed by immunohistochemistry.Finally,average optical density measured by image analysis system were semiquantitatively analysed.Result:After injected intraperitoneally by ADR,the animal appearance dispirited and emaciated for daily.Even some was dead. The lung and liver of survival rats show obvious congestion and their ratio of dry-wet decreasd.This evidence shew lung and liver had obvious congestion. Heart and body weight is proportional to the weight of the experimental group, weight, heart also small in absolute terms, but the relative weight, the weight of the heart than the control group increased significantly, heart weight / weight ratio larger.Obversing the rats myocardium by using HE,In A group,the arrangement of myocardiocytes was in order,transversely striated structure was clear.and,cells were uniform in shape and size.In B group, myocardial nuclear disappeared, myocardial cytoplasm loosed,vacuolar degeneration and granule denaturation can be seen.Additionally,fibrous hyperplasia,myocardium disorder,and myocardial necrosis can be detected.In C group,results shew Astragaloside can raise survival rate and improve heart function.Observation by HE, small amounts cardiac muscular fiber disappeared and cytolysis only be found.But cell hypertrophy, vacuolar degeneration and fibrous hyperplasia were obvious. The apoptosis of cell was detected with TUNEL method and Expression of telomerase reverse transcriptase was observed by immunohistochemistry.Compared with A group,the incindence of cell apoptosis increased(1.84±0.21 vs0.33±0.08,p<0.01) and TERT protein was lower in ADR group(0.765±0.025 vs 2.832±0.054, p<0.01). Compared with ADR group Astragaloside can make apoptosis index of cardiomyocytes lower(0.57±0.14 vs 1.84±0.21 , p<0.05 ) and promote significantly expression of TERT protein(2.194±0.028 vs0.765±0.025,p<0.05).Conclusion: Reduction of telomerase expression and change of telomere length may be involved in the growth reserve of heart in rats with cardiomyopathy. Astragaloside can inhibit the apoptosis of cadiocyte induced by ADR.The mechanism of action might be that it can promote TERT expressing.