sirt1新型受体激动剂SRT2104对受损血管内膜增殖的抑制作用研究

目的 探究不同电压静电纺丝外鞘的微观结构并探讨SRT2104生物可降解血管外鞘对静脉桥血管内膜增殖的抑制作用。 方法 选择5~8 kV、12~15 kV两个电压区间,构建聚乳酸-羟基乙酸共聚物(PLGA)外鞘观察2组微观结构。选取新西兰白兔30只,使用随机数字表法分为对照组、非载药血管鞘组和SRT2104组,每组10只。术后7 d,每组选取4只比较Ki-67荧光染色结果。剩余6只于术后即刻、1周、8周测量血管内径及血流峰值,比较变化率;并比较各组术后8周血管内膜厚度及内膜中膜比值。 结果 电镜下5~8 kV对应的纺丝粗糙,断裂;12~15 kV电压下的纺丝光滑,连续。术后1、8周,SRT2104组内径变化率明显减小(均P<0.01);术后8周SRT2104组变化率也远小于非载药鞘组(P<0.05)。术后1周,SRT2104组血流峰值变化率较小(P<0.05),术后8周该趋势相同;8周末非载药鞘组血流峰值变化率小于对照组(P<0.05)。术后8周HE染色显示SRT2104组膜厚度明显减小(均P<0.01),内膜/中膜比值明显小于对照组及非载药鞘组(均P<0.05),非载药鞘组相比对照组明显减小(P<0.01)。 结论 12~15 kV电压下纺丝具有良好的微观结构,据此构建的SRT2104载药血管外鞘能抑制静脉桥血管内膜增殖。 

A novel sirt1 receptor agonist SRT2104 inhibits the proliferation of the damaged intima

Objective To investigate the microstructure of different voltage electrospinning outer sheath and discuss the inhibitory effect of SRT2104 biodegradable outer sheath on intima proliferation of vein bridge. Methods Two voltage ranges of 5-8 kV and 12-15 kV were selected to construct the outer sheath of PLGA and observe the microstructure. Thirty New Zealand white rabbits were randomly divided into control group, non-drug loading vascular sheath group and SRT2104 group. Seven days after the operation, 4 subjects in each group were randomized to compare the results of ki-67 fluorescence staining. The remaining 6 subjects were measured immediately after the operation, 1 week and 8 weeks, and the rate of change was compared. The intimal thickness and the ratio of intimal media in each group were compared 8 weeks after surgery. Results Under electron microscope, the 5-8 kV spinning was rough and broken, and the 12-15 kV spinning was smooth and continuous. The rate of inner diameter change in SRT2104 group decreased significantly(all P<0.01) 1 and 8 weeks after surgery. The rate of change of SRT2104 group 8 weeks after surgery was also much lower than that of the non-drug carrier group(P<0.05). The change rate of peak blood flow in SRT2104 group 1 week after surgery did not change significantly(P<0.05), and the trend was the same 8 weeks after surgery(P<0.01 vs. control group; P<0.05 vs. non-drug carrier sheath group), the change rate of peak blood flow in the non-drug loading sheath group was lower than that in the control group(P<0.05). HE staining at 8 weeks after surgery showed that the film thickness of SRT2104 group decreased significantly(all P<0.01). Intima-media ratio was significantly smaller(P<0.01 vs. control group; P<0.05 vs. non-drug loading sheath). Compared with the control group, the non-drug carrier sheath group decreased significantly(P<0.01). Conclusion Spinning under 12-15 kV voltage has a good microstructure, and the SRT2104-loaded outer sheath can inhibit the intimal proliferation of vein Bridges.