ABSTRACT
Aim To observe the influence of meisoindi-go on the alteration of Wnt/β-catenin signaling in type 1 diabetic rats ' myocardium and clarify its role in the development of diabetic cardiomyopathy .Methods The type 1 diabetes rat model was established by injec-tion of streptozocin after one-week adaptive feeding . The successful modeling rats were randomly divided in-to DM model group of 4 weeks and 8 weeks, meisoindi-go group of 4 weeks and 8 weeks.Fasting blood glu-cose(FBG) levels were tested.HE staining was used to observe the pathological changes of myocardial struc-tures.The alteration of GSK-3β, p-GSK-3β, Wnt2,β-catenin, NF-κB-p65, p-NF-κB-p65 in myocardium was determined by Western blot and immunohistochem-istry.Results Compared with control group , FBG levels of type 1 diabetic rats significantly increased ( P<0.01 ) , while body weight levels significantly de-creased ( P<0.01 ); compared with DM group , FBG levels of 8 weeks meisoindigo group significantly de-creased ( P <0.01 ) .Myocardial histological analysis revealed that DM induced myocardial focal myocyte hypertrophy , solubility , necrosis , fiber tissue hyperplasi-a; compared with DM group , these symptoms were eased in meisoindigo group of 4 weeks and 8 weeks. Compared with control group , the expression of p-GSK-3β, Wnt2, β-catenin, p-NF-κB-p65 level increased, especially with DM group of 8 weeks(P<0.01).The expression of p-GSK-3β, Wnt2,β-catenin, p-NF-κB-p65 level in meisoindigo group of 4 weeks and 8 weeks decreased significantly(P<0.01).Conclusions The repair effect of meisoindigo on myocardial damage in type 1 diabetic rats may be caused by lowering the ex-pression of proteins in Wnt/β-catenin signaling and in-hibiting the activation of Wnt/β-catenin signaling path-way, participating in the repair of myocardial damage and inflammatory in diabetic rats .Further researches on its mechanism in repairing diabetic myocardial dam-age may find new therapeutic targets for diabetic car-diomyopathy .
ABSTRACT
Aim To explore the mechanism of insulin in combination with selenium preventing myocardial apoptosis in diabetic cardiomyopathy rats .Methods SD rats ( n =50 ) were randomly divided into five groups: control , diabetic cardiomyopathy ( DCM ) , DCM with insulin treatment , DCM with selenium treat-ment, and DCM with insulin and selenium combination treatment .The cell apoptosis was observed by TUNEL . The levels of Bcl-2, caspase-3, PARP, Cbl-b and p38 MAPK were examined by Western blot .The inter-actions of Cbl-b-p38 MAPK and Ku70-Bax were detec-ted by immunoprecipitation .Results Insulin in com-bination with selenium synergistically inhibited apopto-sis, up-regulated Cbl-b, down-regulated p38MAPK ex-pressions and increased the interactions of Cbl-b-p38MAPK and Ku70-Bax.Conclusion Insulin and selenium synergistically inhibit myocardial apoptosis by regulating Cbl-b-inhibited p38 MAPK and preventing Bax translocation .
ABSTRACT
Aim To investigate the effect of astragalo-side IV ( ASIV) on myocardial energy metabolism and mitochondrial biosynthesis in myocardial cells of dia-betic rats induced by streptozotocin ( STZ ) . Methods 50 SD rats at 6 weeks of age were assigned to 5 groups,10 for each group:control group, model group, ASIV 10 mg·kg-1 ·d-1 group, ASIV 20 mg·kg-1 ·d-1 group, ASIV 40 mg·kg-1 ·d-1 group. Except the control group,the remaining 40 were used to estab-lish type 1 diabetes model by the tail vein injection of STZ (35 mg·kg-1 ) . At the end of 16 weeks of treat-ment, left ventricular systolic pressure ( LVSP ) , left ventricular diastolic final pressure ( LVEDP ) and left ventricular maximum rising/falling rate ( ± dp/dtmax ) were tested. Pathological section was observed by HE staining. ATP, ADP, AMP levels were detected by ELISA. The expressions of PGC-1α and NRF-1 protein were assessed by Western blot. The expressions of PGC-1α and NRF-1 mRNA were determined by RT-PCR. Results Compared with control group, model group markedly elevated LVEDP and decreased LVSP, ± dp/dtmax , ATP/AMP and ATP/ADP ratio. Com-pared with model group, low-dose ASIV group did not change significantly,middle-dose ASIV group and high-dose ASIV group obviously decreased LVEDP, and im-proved LVSP, ± dp/dtmax , ATP/ADP and ATP/AMP ratio. Meanwhile, the expressions of PGC-1α and NRF-1 protein and mRNA were increased in a dose-de-pendent manner. Conclusion ASIV could promote mitochondrial biosynthesis, improve energy metabolism in myocardial cells of type 1 diabetic rats by PGC-1αand NRF-1 .