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Objective To investigate the neuroprotective effect and possible mechanism of nicorandil in mice under deep hypothermic low flow (DHLF). Methods A total of 105 3-week-old male C57/BL-6 mice were randomly divided into 7 groups: sham operation, model, nicorandil (5, 10, and 20 mg/kg), nicorandil 20 mg/kg + LY294002, and LY294002 groups (n = 15 in each group). A DHLF model was induced. At 24 h after reperfusion, the brain tissues of mice were taken out for HE and TUNEL staining. The pathological changes of cerebral cortical neurons and apoptosis were observed. Western blot was used to detect the expression levels of the total Akt, phospho-Akt (p-Akt), Bcl-2, and Bax. Results HE pathological staining showed that cortical neuronal injury was reduced, the phenomena of cel membrane depression, nuclear condensation, concentrated dye, and the blurring of the nucleus were decreased significantly in nicorandil group. The morphology of neurons was basicaly restored to normal. TUNEL staining showed that the apoptosis index in various dose groups of nicorandil was decreased significantly compared with the model group (al P < 0. 05). Western blot analysis showed that the expression levels of p-Akt and Bcl-2 proteins increased significantly in various dose groups of nicorandil compared with the model group (al P < 0. 05), and the expression level of Bax protein was decreased significantly (al P < 0. 05 ). After adding the phosphatidylinositol 3-kinase (PI3K) specific inhibitor LY294002, there was no significant difference in neurons pathological injury in the cortex compared with the model group. There was no significant difference in the apoptosis index, and the expression levels of p-Akt, Bcl-2, and Bax compared with the model group. Conclusions Nicorandil has a certain neuroprotective effect in mice under DHLF. Its mechanism may be associated with the activation of PI3K/Akt signaling pathway, and then further regulation of the downstream protein Bcl-2 and Bax expression.
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Objective To observe the expression changes of 12 ischemia-related microRNAs (miRNA) in cerebral ischemia-reperfusion injury after deep hypothermic low flow (DHLF) in mice.Methods A total of 80 3-w eek-old healthy and clean grade C57BL/6 male mice w ere randomly divided into either a DHLF model group or a sham operation group. Each group w as redivided into 4 subgroups according to the time points of 2, 6, 12, and 24 h (10 in each group). The bilateral carotid arteries of the DHLF model group w ere clipped and a DHLF model w as established, w hile the carotid arteries of the sham operation group w ere not clipped. The mice w ere sacrified at each time point and the brain tissue w as removed. The total RNA w as extracted. Quantitative reverse transcriptase polymerase chain reaction w as used to detect miRNA expression. Results Compared w ith the sham operation group, the expression levels of 9 miRNAs w ere upregulated, 2 w ere dow n-regulated, and 1 did not have any significant change in the DHLF model group. Conclusions The expression levels of 11 miRNAs changed significantly after DHLF. It might have a regulatory role in cerebral ischemia-reperfusion injury after DHLF.
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Objective To study the change of the eonnxin43 expression in the heart of diabetic mellitus rats. Methods STZ-in-dueed diabetic mellitus in rats were developed. The expression of connexin43 in the heart was detected by immunohistochemistry and image analysis, and the heart function was observed by electrophysiolograph and echocardiogram. Results During the course of diabetic mellitus, the expression of connexin43 in the heart of diabetic rats decreased respectively in the 12th week and 24th week (P<0.01). The values of dp/dtmax and + dp/dtmax in group DM in the 12th week and 24th week were lower than that in normal control group respectively (P<0.01), and the LVEF were also decreased (12w P<0.05,24w P<0.01). The analysis of correlation showed that the expression of con-nexin43 in heart were positively correlated with heart function (P<0.05) . Conclusion The expression of Connexin43 evidently de-creased in the hearts of diabetic rats and it is positively correlated with the heart function.
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Insulin sensitivity,β-cell function and serum high-sensitivity C-reactive protein (hs-CRP)levels were observed in obese and non-obese normoglycemic first-degree relatives of type 2 diabetic patients (FDR). The results showed that there existed insulin resistance,β-cell dysfunction and increased serum hs-CRP level in obese FDR of type 2 diabetic patients. Moreover, insulin resistance and increased CRP level were positively related to waist circumference.
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Objective To investigate the effects of glycemic control on myocardial glucose metabolism in type 2 diabetic rats. Methods Eighteen male Sprague-Dawley rats were divided into three groups:control, diabetes, therapy.Fed with high-fat diet and intraperitoneally injected with streptozotocin to establish type 2 diabetic model,the rate of carbohydrate oxidation was measured by isolated heart Langendorf perfusion apparatus, the expression level of glucose transport 4(GLUT4) was measured by Western blotting. Results Compared with the control group,the diabetic rats had a significantly depression of glucose uptake in the hearts(P
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AIM: To study the effect of rosiglitazone (RSG) to improve insulin sensitivity on myocardial energy substrate utilization as well as the cardiac function in a rat model of type 2 diabetes mellitus. METHODS: Sprague-Dawley rats were conducted into three groups: chow-fed rats were fed with normal chow (12% of calories as fat); fat-fed/STZ rats were fed with high-fat diet (40% of calories as fat) for 4 weeks and then injected with streptozotocin 35 mg/kg intraperitoneal; fat-fed/STZ/RSG rats were fat-fed/STZ rats treated with rosiglitazone (3 mg?kg~(-1)?d~(-1)) for 2 weeks. A cannula connected to a passive transducer was inserted the heart for the measurement of the cardiac function including heart rate (HR), left ventricular end-diastolic pressure (EDP) and ?dp/dt_(max). Then the isolated hearts were mounted onto a Langendorff perfusion apparatus to perfuse with Krebs-Henseleit buffer in the presence of 5 mmol/L glucose and 0.4 mmol/L [~3H] labelled palmitate. Glucose uptake and [~3H_2O] collection were measured to evaluate the rate of carbohydrate and fatty acid oxidation. RESULTS: Compared with the chow-fed rats, fat-fed/STZ rats had a significantly depression of glucose uptake in the hearts [(54.7?6.2 vs 69.0?5.7) ?mol?g~(-1) dry weight, P
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CT and TT genotype frequencies of TNF-? gene at -857 site in obese patients with type 2 diabetes mellitus (DM)andcontrolgroupswithoutobesity were 0.396, 0.020 and 0.179, 0.000, and T allele 0.220 and 0.090, respectively. This finding suggests that mutation is associated with type 2 DM in obese subjects.