Department of Cardiology, Zhejiang Hospital, Hangzhou, Zhejiang, China.
Department of Cardiology, Zhejiang Hospital, Hangzhou, Zhejiang, China.
Am J Med Sci. 2019 Apr;357(4):323-332. doi: 10.1016/j.amjms.2019.01.014. Epub 2019 Jan 31.
This study assessed the effect of ibandronate (IBN), a farnesyl pyrophosphate synthase (FPPS) inhibitor, on vascular remodeling in diabetic rats.
A rat model of diabetes was induced by a high-fat and high-sugar diet combined with a small dose of streptozotocin. The diabetic rats received 5 µg/kg of ibandronate solution or normal saline subcutaneously every morning for 16 weeks. The morphology of the thoracic aorta was assessed by hematoxylin and eosin and Masson's trichrome staining techniques. Gene expression levels of connective tissue growth factor (CTGF) and FPPS were assessed by quantitative real-time polymerase chain reaction (qRT-PCR) analysis. CTGF and FPPS protein levels were determined by Western blotting analysis.
Rats with diabetes mellitus showed moderate hyperglycemia, insulin resistance, hyperlipidemia and thoracic aortic fibrosis. FPPS was significantly upregulated in the thoracic aorta from diabetic animals. Interestingly, IBN treatment for 16 weeks alleviated the diabetes-induced histopathologic changes in the thoracic aortic wall and reduced CTGF protein and mRNA levels.
These findings provided evidence that FPPS is involved in thoracic aortic fibrosis in diabetic rats. Meanwhile, IBN could alleviate vascular remodeling in diabetic animals.
本研究评估了法呢基焦磷酸合酶（FPPS）抑制剂伊班膦酸盐（IBN）对糖尿病大鼠血管重塑的影响。
通过高脂肪高糖饮食联合小剂量链脲佐菌素诱导大鼠糖尿病模型。糖尿病大鼠每天早上接受 5μg/kg 的伊班膦酸盐溶液或生理盐水皮下注射，共 16 周。采用苏木精和伊红及 Masson 三色染色技术评估胸主动脉形态。采用实时定量聚合酶链反应（qRT-PCR）分析评估结缔组织生长因子（CTGF）和 FPPS 的基因表达水平。采用 Western blot 分析测定 CTGF 和 FPPS 蛋白水平。
糖尿病大鼠表现出中度高血糖、胰岛素抵抗、高脂血症和胸主动脉纤维化。糖尿病动物的胸主动脉中 FPPS 明显上调。有趣的是，16 周的 IBN 治疗缓解了糖尿病引起的胸主动脉壁的组织病理学变化，并降低了 CTGF 蛋白和 mRNA 水平。
这些发现提供了证据表明 FPPS 参与了糖尿病大鼠的胸主动脉纤维化。同时，IBN 可以减轻糖尿病动物的血管重塑。
