| Objective: 1. To investigate the myocardial overexpression of LXRs can alleviate the myocardial apoptosis and inflammation during the progression of diabetic cardiomyopathy. 2. To investigate the overexpression of LXRs can alleviate the myocardial apoptosis and inflammation by inhibiting the activity of NF-κB.Methods: 1.We randomized 120 wistar male rats(approximate 100 g body weight,4weeks old) into 6 groups(n=20): normal rats+DMSO, normal rats+normal saline, diabetic cardiomyopathy+DMSO, diabetic cardiomyopathy+normal saline, diabetic cardiomyopathy+DMSO+T0901317, normal rats+ DMSO+T0901317. Throughout the study, The control group was fed the basal diet, the other group a high fat diet. Diabetes was induced by a single intraperitoneal injection of 30 mg/kg body weight of STZ in adult wistar rats after 4 weeks later. 2. We can use electron microscope and light microscope to observe the change of myocardial fibrosis. The activity of LXRs and NF-κB were measured by Electrophoretic Mobility Shift Assay(EMSA). The m RNA expression of TNF-α, IL-6 were detected by PCR. The Western blot were employed to detect the expression of Caspase-3 protein;Results: 1. Measurement of myocardial fibrosis: When compare with the control rats, diabetic rats showed elevate the collagen levels of myocardial cells. The experimental group show discreased interstitial cardiac fibrosis as compared with the diabetic rats. 2. Transmission Electron Microscopy: When compare with the control rats, diabetic rats showed severe damage of the left ventricular ultrastructure, including destruction of myofibrils, swollen mitochondria with disorganized cristae, excess glycogen lysis and accumulated lipids. When compare with the diabetic rats, the experimental group show silenced reversed myocardial remodeling.3.The activity of LXRs: When compare with the control rats, diabetic rats showed reduce the activity of LXRs(P<0.05), The experimental group show elevated the activity of LXRs as compared with the diabetic rats(P<0.05).There were no difference between the diabetic cardiomyopathy+normal saline group and the diabetic cardiomyopathy+DMSO group(P>0.05). And also no difference between the normal rats+DMSO+T0901317 group and the diabetic cardiomyopathy+DMSO+T0901317 group(P>0.05). 4.The activity of NF-κB: When compare with the control rats, diabetic rats showed elevate the activity of NF-κB(P<0.05), The experimental group show reduced the activity of NF-κB as compared with the diabetic rats(P<0.05).There were no difference between the diabetic cardiomyopathy+normal saline group and the diabetic cardiomyopathy+DMSO group(P>0.05). When compare with the normal rats+T0901317+DMSO group, the experimental group show elevated the activity of NF-κB(P<0.05). 5. ELISA: When compare with the control rats, diabetic rats showed elevated m RNA levels of TNF-α and IL-6.(P<0.05), The experimental group show reduce the m RNA levels of TNF-α and IL-6 as compared with the diabetic rates(P<0.05).There were no difference between the diabetic cardiomyopathy+normal saline group and the diabetic cardiomyopathy+DMSO group(P>0.05). When compare with the normal rats+T0901317+DMSO group, the experimental group show elevated m RNA levels of TNF-α and IL-6(P<0.05). 6.Western Blot: When compare with the control rats, diabetic rats showed elevated the protein expression of Caspase-3.(P<0.05), The experimental group show reduce the protein expression of Caspase-3 as compared with the diabetic rats(P<0.05).There were no difference between the diabetic cardiomyopathy+normal saline group and the diabetic cardiomyopathy+DMSO group(P>0.05). When compare with the normal rats+T0901317+DMSO group, the experimental group show elevated the protein expression of Caspase-3(P<0.05).Conclusions: 1. T0901317 can alleviate the myocardial apoptosis and inflammation during the progression of diabetic cardiomyopathy.2. Overexpression of LXRs can alleviate the myocardial apoptosis and inflammation by inhibiting the activity of NF-κB. |
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