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抑制神经酰胺合成可逆转链脲佐菌素诱导的糖尿病大鼠的血管内皮功能障碍和动脉粥样硬化。

Inhibition of ceramide synthesis reverses endothelial dysfunction and atherosclerosis in streptozotocin-induced diabetic rats.

机构信息

Department of Endocrinology, Xiangya Hospital of Central South University, Hunan Province, Xiangya Street 78, Changsha 410008, China.

出版信息

Diabetes Res Clin Pract. 2011 Jul;93(1):77-85. doi: 10.1016/j.diabres.2011.03.017. Epub 2011 Apr 13.

Abstract

OBJECTIVES

To explore the effect of myriocin on EDVD and atherosclerosis in diabetic rats.

METHODS

Rats were fed with a high-fat/high-sucrose/high-cholesterol diet (20% sucrose, 10% animal oil, 1.0% bile salt and 2.5% cholesterol) (hereinafter defined as diabetic groups) or Purina Rodent Chow (NC group), the former was intervened with low dose streptozotocin (30 mg/kg) after feeding 1 month to make diabetic model. The NC group was intervened with citrate buffer and the diabetic rats were intervened with myriocin (0.3 mg/kg Qod) (MTD group) or just solvent (DC group) for 14 weeks. The EDVD, thickness of fatty deposition under endothelium, ceramide, PI3K/PKB/eNOS, NO and other vital parameters were measured after the rats sacrificed.

RESULTS

In DC group, the ceramide contents in serum and aorta increased, the EDVD was impaired, the fatty deposition under endothelium increased, and the phosphorylation of PI3K/PKB/eNOS and NO release decreased all compared with the NC group (P<0.05). Compared with the DC group, the ceramide contents in MTD group decreased, the EDVD ameliorated, the fatty deposition diminished, and PI3K/PKB/eNOS phosphorylation and NO release (P<0.05) increased.

CONCLUSIONS

After treated with myriocin, the EDVD in diabetic rats has been improved by increasing PI3K/PKB/eNOS phosphorylation and NO release, and meanwhile the atherosclerosis has reversed.

摘要

目的

探讨曲古抑菌素对糖尿病大鼠 EDVD 和动脉粥样硬化的影响。

方法

大鼠给予高脂肪/高蔗糖/高胆固醇饮食(20%蔗糖、10%动物油、1.0%胆盐和 2.5%胆固醇)(以下简称糖尿病组)或 Purina 啮齿动物饲料(NC 组),喂养 1 个月后用低剂量链脲佐菌素(30mg/kg)干预制作糖尿病模型。NC 组用柠檬酸缓冲液干预,糖尿病大鼠用曲古抑菌素(0.3mg/kg Qod)(MTD 组)或溶剂(DC 组)干预 14 周。处死大鼠后测量 EDVD、内皮下脂肪沉积厚度、神经酰胺、PI3K/PKB/eNOS、NO 等重要参数。

结果

在 DC 组中,与 NC 组相比,血清和主动脉中的神经酰胺含量增加,EDVD 受损,内皮下脂肪沉积增加,PI3K/PKB/eNOS 磷酸化和 NO 释放减少(P<0.05)。与 DC 组相比,MTD 组的神经酰胺含量降低,EDVD 改善,脂肪沉积减少,PI3K/PKB/eNOS 磷酸化和 NO 释放增加(P<0.05)。

结论

用曲古抑菌素治疗后,糖尿病大鼠的 EDVD 通过增加 PI3K/PKB/eNOS 磷酸化和 NO 释放而得到改善,同时动脉粥样硬化得到逆转。

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