波生坦对糖尿病小鼠心肌组织纤维相关生长因子的影响

Effect of Bosentan on expression of fibrotic related growth factors of myocardial tissue in diabetic mice

目的探讨波生坦对糖尿病小鼠心肌组织纤维相关生长因子的影响。方法将6周龄雄性C57BL/6小鼠分为3组:对照组、糖尿病组、糖尿病+波生坦组,每组15只。链脲佐菌素(streptozotocin,STZ)按70 mg/kg单次剂量腹腔注射。在STZ注射后即刻、1周、2周测定小鼠的空腹血糖,以确定糖尿病模型是否建立。在STZ注射后第2天糖尿病+波生坦组小鼠灌胃波生坦(100 mg/kg),其余两组灌胃等量的0.9%氯化钠注射液直到16周。应用反转录酶-聚合酶连锁反应检测转化生长因子(transforming growth factor beta,TGF-β)、结缔组织生长因子(connective tissue growth factor,CTGF)、血管内皮生长因子(vascular endothelial growth factor,VEGF)及胶原蛋白1(Collagen-1)的m RNA的表达。结果 16周后,测量小鼠空腹血糖,糖尿病组与糖尿病+波生坦组接近(P>0.05),两组血糖与对照组相比显著增高(P<0.01)。糖尿病+波生坦组心脏VEGF的m RNA水平较糖尿病组增高(P<0.05),糖尿病+波生坦组与糖尿病组相比,心肌纤维相关因子TGF-β、CTGF及Collagen-1的mRNA水平较低(P<0.05)。结论内皮素受体拮抗剂波生坦能降低心肌纤维相关生长因子的表达。

Objective To explore the effect of Bosentan on the expression of fibrotic related growth factors of myocardial tissue in diabetic mice. Methods Male 6-week old C57BL/6 mice were divided into 3 groups： control group, diabetes mellitus（DM） group and DM-B group（diabetes with bosentan group）, 15 in each group. Streptozotocin（STZ） was injected intraperitoneally accounting for 70 mg/kg for single dose which was used to confirm that diabetes was induced in the mice, fasting blood glucose（FBG） was measured at 0-, 1-, 2-week after STZ injection. The second day after STZ injection, mice in DM-B group underwent intragastric administration of Bosentan（100 mg/kg）, mice in the rest of the two groups were injected with the same amount of saline lavage for 16 weeks. RT-PCR was applied to detect transforming growth factor beta（TGF-β）, connective tissue growth factor（CTGF）, vascular endothelial growth factor（VEGF） and the expression of RNA（mRNA） which was the messenger of collagen protein 1（collagen- 1）. Results After 16 weeks, fasting blood glucose in mice of DM group and DM-B group was measured which was similar without significant differences（P〉0.05）, but it was significantly higher in these two groups when compared with control group（P〈0.01）. Compared with DM group, the cardiac VEGF mRNA level in DM-B group was significantly higher（P〈0.05）, and the expression of fibrotic related growth factors TGF-β, CTGF and collagen-1 was significantly lower（P〈0.05）. Conclusion These findings suggest that endothelin receptor antagonists Bosentan can reduce the expression of fibrotic related growth factors of myocardial tissue in diabetic mice.