NF-κB经典信号通路介导铁过载对沙鼠心肌细胞线粒体的损伤

Mechanism research on iron overload damage to mitochondriaof myocardial cell

目的通过检测铁过载沙鼠心肌细胞内NF-κB经典信号通路关键物质的水平及电镜观察线粒体损伤程度,探索NF-κB经典信号通路是否介导了铁过载损伤心肌细胞线粒体的过程。方法将24只蒙古沙鼠随机分为4组,分别为对照组(不进行任何干预)、溶剂对照组(腹腔注射生理盐水)、铁过载组(腹腔注射右旋糖酐铁16周)及铁过载+PDTC组(腹腔注射右旋糖酐铁,同时注射PDTC 16周)。Western blot方法检测心肌细胞中NF-κB经典信号通路的关键物质IκB-α、p-IκB-α、胞浆p65及胞核p65的水平;电镜观察各组心肌细胞线粒体形态学改变并行Flameng评分。结果 (1)与其它3组比较,铁过载组p-IκB-α、胞浆p65水平降低,胞核p65水平明显增高,差异有显著性(P<0.05);(2)铁过载组线粒体Flameng评分高于其它3组,差异有显著性(P<0.05);铁过载+PDTC组线粒体Flameng评分高于对照组和溶剂对照组,但低于铁过载组,差异有显著性(P<0.05)。结论铁过载能够激活沙鼠心肌细胞NF-κB经典信号通路,从而损伤心肌细胞线粒体。

Objective To explore whether NF-κB typical signal pathway mediates the process of iron overload damage to mitochondria of myocardial cell by detecting the level of key substances of NF-κB signal pathway and the degree of damage to mitochondria under observation of electronic microscope in iron overload gerbil cardiomyocytes. Methods Twenty four Mongolian gerbils were divided into 4 groups randomly, including the control group （without any intervention）, solvent control group （intraperitoneal injection of physiological saline）, iron overload group （intraperitoneal injection of iron dextran for 16 weeks）, and iron overload ＋ PDTC group （intraperitoneal injection of iron dextran, with injection of PDTC for 16 weeks as well）. The levels of key substances, IKB-α, p-IκB-α, cytoplasm p65 and nuclei p65, in NF-KB typical signal pathway of cardiomyocytes were detected by western blot; the damage of cardiac muscle mitochondria was observed with electronic microscope, and Flameng scores was counted. Results （1） Compared with the other 3 groups, the levels of p-IκB-c~ and cytoplasm p65 in the iron overload group were decreased, the level of nuclei p65 was significantly increased, and the difference was statistically significant （P 〈 0. 05 ） ; （2） Flameng scores of mitochondria in the iron overload group were higher than those in the other 3 groups, and the difference was statistically significant （ P 〈 0.05 ） ; Flameng scores of mitochondria in the iron overload ＋ PDTC group were higher than those in the control group and the solvent control group, but lower than those in the iron overload group, and the difference was statistically significant （P 〈 0.05 ）. Conclusions Iron overload can activate NF-κB typical signal pathway of gerbil cardiomyocytes and damage the cardiac muscle mitochondria.