氧化/还原修饰肝素对高糖诱导肾小球系膜细胞凋亡及其信号转导途径的影响(英文)

Influence of OR-heparin,a chemically modified heparin,on high glucose-induced mesangial cell apoptosis and its signal transduction pathway

目的:考察化学修饰的非抗凝肝素(高碘酸氧化/硼氢化钠还原修饰肝素,OR-Heparin)对高糖诱导的人肾小球系膜细胞凋亡的保护作用及其可能的机制。方法:肾小球系膜细胞经高糖或高糖+OR-heparin作用24 h,Hoechest 33258染色、Annexin V-PI双染流式细胞仪检测细胞凋亡,Western blotting检测凋亡相关蛋白(p53,Bcl-2,Bax,cytosolic cytochromeC)的表达,Cy3-标记抗体荧光显微镜观察NF-κB的转录激活,比色法测定Caspase-3酶活。结果:氧化/还原修饰的肝素显著降低高糖诱导的肾小球系膜细胞的凋亡,同时抑制凋亡相关蛋白的表达以及NF-κB的转录激活。结论:氧化/还原修饰肝素可以通过抑制凋亡相关蛋白的表达来抑制高糖诱导的肾小球系膜细胞凋亡,这可能与抑制NF-κB转录激活相关。

Aim： To investigate whether chemically modified non-anticoagulation heparin derivate （periodate oxidation/borohydride reduction-modified heparin （OR-heparin）） could inhibit high glucose-induced human mesangial cell apoptosis and to explore its possible mechanism. Methods： Mesangial cells were exposed to high glucose or high glucose with OR-heparin for 24 h. Apoptosis was evaluated by Hoechst 33258 staining and Fluoresent activated cell sorting analysis. The expressions of apoptosis-related proteins （p53, Bcl-2, Bax, cytosolic cytochrome C） were determined by Western blotting. NF-κB translocation was observed under fluorescence microscopy by using Cy3-1abeled antibody. Caspase-3 activity was detected by colorimetry. Results： OR-heparin significantly inhibited high glucose-induced mesangial cell apoptosis and the expression of apoptosis-related proteins. It also blocked NF-κB translocation induced by high duced mesangial cell apoptosis through inhibiting the the blockage of the translocation of NF-κB. glucose. Conclusion： OR-heparin inhibits high glucose-inexpression of apoptosis-related proteins and it may be due to