Apelin-13减轻糖尿病小鼠主动脉损伤

Attenuating effects and mechanisms of apelin-13 on aortic injuries in diabetic mice

目的探讨apelin-13对糖尿病小鼠主动脉结构的影响及其机制。方法对照组:8周龄C57/BL6j小鼠6只;糖尿病组:8周龄kk Ay小鼠6只;apelin-13处理组:kk Ay小鼠6只,皮下埋微量植渗透泵释放apelin-13[30μg/(kg·d)]。4周后取材,进行HE、Masson染色,光学显微镜下观察血管的形态学改变及胶原纤维的沉积情况,弹性蛋白染色观察血管弹力纤维板的形态学改变,免疫组织化学染色分析血管内信号蛋白转化生长因子β1(TGF-β1)的表达水平。结果与正常对照组相比,糖尿病组小鼠血管壁中膜明显增厚,主动脉内胶原纤维含量明显升高(P<0.05),弹力纤维排列紊乱、断裂,同时血管壁TGF-β1表达增强(P<0.05),而apelin-13处理组小鼠血管壁中膜较糖尿病组明显变薄,血管间质内胶原纤维的含量较糖尿病组小鼠显著下降(P<0.05),弹力纤维排列较整齐,血管壁TGF-β1表达也显著下调(P<0.05)。结论外源性Apelin-13可能通过抑制TGF-β1以及平滑肌细胞增殖减轻糖尿病引起的主动脉纤维化以及血管中膜弹力纤维损伤。

Objective To observe the effects and mechanisms of apelin-13 on aortic fibrosis in diabetic mice.Methods Eighteen mice were divided into three groups： control group： C57/BL6 jmice in eight weeks old（ n = 6）,diabetic group： kk Ay mice in eight weeks old（ n = 6）,and apelin-13 group： kk Ay mice implanted with osmotic pump to release apelin-13 at the rate of 30μg/（ g·d）. After 28 days,the aortas were harvested and fixed. Morphological changes and collagen deposition were observed with HE and Masson staining. The aortic elastic fibers were observed with elastin staining. Expression of transforming growth factor-β1（ TGF-β1） was measured with immunohistochemical staining. Results Compared to the control group,the wall of aorta in diabetic mice thickened,the collagen deposite in diabetic mice was significantly more than that in control mice（ P 〈 0. 05）. The elastin in diabetic mice was irregularly arranged. The levels of TGF-β1 in the aorta of diabetic mice were significantly more than that in control mice（ P 〈 0. 05）. After apelin-13 treatment,the wall of the aorta in diabetic mice became thinner,the collagen deposite was significantly improved than that in diabetic mice（ P 〈 0. 05）,while apelin-13 reset the elastin of aorta in diabetic mice,and reduced TGF-β1 expression to almost normal levels（ P 〈 0. 05）. Conclusion Apelin-13 may attenuate fibrosis and elastin breakdown in the aorta in diabetic mice by inhibit TGF-β1 expression and proliferation of smooth muscle cells in medium of the aortic wall.