ABSTRACT
Objective: To study the protective effect and mechanism of compound Danshen dropping pills on the heart of rats with type 2 diabetic cardiomyopathy. Method: Seventy-five male SD rats were randomly divided into blank group (15 rats) and model group (60 rats). The model group was fed with high-sugar and high-fat diet, high-sugar and high-fat milk and sucrose water. Six weeks later, rats with foodborne obesity (body mass ≥ the mean body mass of blank control group + 2 times standard deviation) were selected and intraperitoneally injected with 1% streptozotocin (STZ)28 mg·kg-1. After 12 weeks, rats with fasting blood glucose ≥ 11.1 mmol·L-1 and polydipsia, diuresis, polyphagia and weight loss were randomly divided into model group, compound Danshen dropping pills group (0.5 g·kg-1) and metformin group (0.5 g·kg-1) and intervened for 12 weeks. At the end of the experiment, echocardiography was used to evaluate cardiac function. Blood samples were taken to determine the corresponding biochemical indicators of rats. Histopathological changes of myocardium were observed by hematoxylin-eosin (HE) and Masson staining. The ultrastructure of myocardium was observed under electron microscope. Western blot was used to detect the expressions of vascular endothelial growth factor (VEGF), transforming growth factor-beta 1 (TGF-β1) and type Ⅰ collagen (Collagen Ⅰ). Real-time fluorescence quantitative analysis (Real-time PCR) was used to detect the expression of miRNA-200b. Result: Compared with the blank group, the heart weight index (HMI), fasting blood glucose (FBG), glycosylated hemoglobin (HbA1c), fasting insulin (FINS), total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterin(LDL-C) levels in the model group were significantly increased (PPPPPβ1 and Collagen I increased (PPPPPPβ1 and Collagen I was decreased (PPConclusion: Compound Danshen dropping pills may play a protective role in the heart of type 2 diabetic cardiomyopathy rats by lowering lipid, up-regulating the expression of miR-200b and inhibiting the expression levels of VEGF, TGF-β1 and Collagen I.
ABSTRACT
Objective To compare sensitive difference of docetaxel between the triple negative breast cancer (TNBC) cell line CAL-51 and non TNBC line T47D and analyze mechanisms underlying docetaxel resistance in former cells. Methods Cell activity was determined by MTT method and IC50 value was calculated; Wright-Giemsa stain was used to analyze the effect of docetaxel in the morphology of CAL-51 and T47D cell lines. Flow cytometry (FCM) was performed to determine cell cycle distribution and apoptosis. Realtime fluorescence quantitative PCR was used to compare the relative gene expression levels. The anti-apoptosis protein Bcl-2 and caspase family protein expression levels were determined by Western blot. Results Wright-Giemsa stain showed significant morphology change in T47D cells by docetaxel treatment. Further flow cytometry results confirmed that docetaxel could significantly induce apoptosis in T47D cells compared to CAL-51 cells (P< 0.01). The result of realtime fluorescence quantitative PCR revealed that anti-apoptosis protein Bcl-2 was significantly higher expressed in CAL-51 cells (P<0.05). Immunoblot analysis revealed docetaxel treatment induced the instrinsic pathways in both CAL-51and T47D cells, but the activated pathway of executioner caspase was different. Conclusion Our present study shows that docetaxel induces different intrinsic apoptosis pathway in CAL-51 and T47D cell lines. Anti-apoprosis protein Bcl-2 is highly expressed, which might be the underlying mechanism of docetaxel resistance in TNBC cell line-CAL-51.