Study the Apoptotic Effect of Dialysis Peritonitis Effluents from ESRD Patients in Cultured Cardiomyocytes

• Main Authors: Yi-Chien Yeh, 葉怡倩
• Other Authors: Jau-Ling Huang
• Format: Others
• Language: zh-TW
• Published: 2008
• Online Access: http://ndltd.ncl.edu.tw/handle/31777200435487051685

碩士 === 長榮大學 === 醫學研究所 === 96 === Cardiac disease is the leading cause of death among patients receiving long-term continuous ambulatory peritoneal dialysis（CAPD）, especially in patients with frequent peritonitis. We proposed that the peritonitis toxins might enter the systematic circulation, and lead to heart diseases. The purpose of this study was to explore whether the peritonitis effluents of end-stage renal disease（ESRD）patients theraping with CAPD could induce cytotoxicity in H9c2-cultured cardiomyoblast. The results showed a dose-dependent cell death in H9c2 cells treated with peritonitis effluents. The effect of peritonitis effluents in H9c2 cells was studied by flow cytometric analysis. The results of proidium iodide stain showed that the percentage of the cells arrested at G2/M phase were obviously higher then that of untreated cells. The proidium iodide stain also showed that the peritonitis effluent could increase the cells of sub-G1 phase. Annexin V analysis furthere demonstrated that peritonitis effluents could induce an apoptosis response. Real-time RT-PCR and western blot analysis showed that the peritonitis effluents could reduce the expression of GATA-4, a cardiac important transcription factor, and then to affect the expression level of its downstream target Bcl-2, the anti-apoptotic regulator. The western blot also showed that the peritonitis effluents could increase the expression of pro-apoptosis regulator Bax in H9c2 cells. These results suggested that peritonitis effluents could be cardiotoxic and function as an apoptotic inducer. Peritonitis toxins might through perturb the ratio of Bax / Bcl-2 through GATA-4 transcription factor to cause the death of cardiomyocytes.