人血管平滑肌细胞PGC-1/NRF-1/mtTFA的表达

BACKGROUND: Mitochondria may participate in the complex process that vascular smooth muscle cells transform tram contractile state to synthetic state. OBJECTIVE: To observe the effect of PGC-1/NRF-1/mtTFA pathway associated with mitochondrial function on the proliferation of vascular smooth muscle cells. DESIGN, TIME AND SETTING: Contrast observation was conducted in January 2007 at Central Laboratory, the First Affiliated Hospital of China Medical University. MATERIALS: Oxidized low-density lipoprotein (Xiehe Institute of Chinese Academy of Sciences, China); sodium azide (Shenyang Branch of Sinopharm Chemcial Reagent Co., Ltd., China); smooth muscle cells of human umbiblical artery (Wuhan Uscn Sciences Co., Ltd., China). METHODS: There were 4 groups in the experiment, the control group was given normal medium; oxidized low-density lipoprotein group was treated by routine medium supplemented with 10 mg/L oxidized low-density lipoprotein for 24 hours; in antisense PGC-1 group, based on the oxidized low-density lipoprotein intervention, cells were seeded on a 6-well plate at the density of 1×10^8L^(-1), and then added prepared 70 μL antisense PGC-1 oligonucleotide liposome complex, and added fetal bovine serum and medium 6 hours later; in sodium azide group, cells were treated by medium supplemented with 10 mg/L oxidized low-density lipoprotein and 32 mmol/L sodium azide for 24 hours. MAIN OUTCOME MEASURES: The expression of PGC-l. NRF-l and mtTFA protein of cultured cells after intervention in each group were detected by western blotting. Changes of mitochondrial function were observed after intervention in each group. Cell viability was detected by methyl thiazolyl tetrazolium colorimetric assay. RESULTS: Compared with control group, the expression of PGC-1, NRF-1 and mtTFA protein, enzyme activity of mitochondrial cytochrome c oxidase and cell proliferation activity increased in the oxidized low-density lipoprotein group (P＜0.05), Compared with oxidized low-density lipoprotein group, the expression of PGC-1, NRF-1 and mtTFA protein, enzyme activity of mitochondrial cytochrome c oxidase and cell proliferation activity decreased in the antisense PGC-1 group (P＜0.05). In the sodium azide group, the expression of PGC-1, NRF-1 and mtTFA protein, enzyme activity of mitochondrial cytochrome c oxidase decreased (P＜0.05), cell proliferation was inhibited (P＜0.05). CONCLUSION: PGC-1/NRF/mtTFA signal transduction pathway influences the growth status of cells through changing the mitochondrial function in the proliferation of human vascular smooth muscle cells.