胱胺酸對狼瘡小鼠心臟凋亡之影響及相關機制探討

紅斑性狼瘡是一種自體免疫性疾病，研究報告指出紅斑性狼瘡會造成許多器官受到嚴重的傷害，其中罹患紅斑性狼瘡可能會使心肌細胞受損，而心肌細胞的受損會造成心臟功能的衰退，進而引起心臟疾病的主要因素，而細胞凋亡在發病的過程中扮演著重要的角色，文獻指出TG2與凋亡相關，TG2可能與全身性紅斑性狼瘡病理有關，而胱胺是TG2的抑制劑，因此本篇利用胱胺來探討全身性紅斑性狼瘡在心臟所扮演的角色為何?我們將28週大的BALB/c和NZB/W F1 小鼠連續14天注入胱胺，分析BALB/c和NZB/W F1 小鼠生理和病理的變化我們利用二維電泳及Western Blot分析發現胱胺可以降低CKMB蛋白的表現，進而改善心肌受損的現象，接著我們再探討心肌細胞的肥大和凋亡的現象，從生理數據發現胱胺可以降低狼瘡鼠心肥大的現象而我們也利用western Blot和二維電泳分析也發現胱胺可以降低FABP蛋白的表現量及ANP蛋白的表現量，另外在誘導肥大的路徑IL6 MEK5-ERK5及MAPK也可看到相同的結果。在TUNEL assay中可以觀察到胱胺可以減少心肌細胞的凋亡，同時我們也利用Western Blot證明胱胺可以減少心肌細胞的凋亡是透過Deth receptor和Mitochondria這兩條路徑，而這樣子降低凋亡的現象很有可能與NF-kB這訊息傳遞的分子上升有關，因此胱胺確實具有保護心肌細胞的作用，可改善心肌細胞肥大、凋亡的情形。

關鍵字

胱胺酸；紅斑性狼瘡；心臟凋亡

並列摘要

Systemic lupus erythematosusb is an autoimmune disease, stuies indicate that SLE can cause serious organ damage, Especially suffering from SLE may cause which is the cause of decline of cardiac fuction. This is the main factor in heart disease. Apotosis in the course of the disease plays an important role, Studies point out apoptosis is related to TG2, at the same time TG2 may be associated with SLE , and cystamine is the TG2 inhibitor. Therefore the main discuss is through use of cystamine about the relation between SLE and heart .The 28-week-old BALB/c and NZB/W F1 mice are injected with cystamine for 14day in a row, we analysis BALB/c and NZB/W F1 mice physical and pathology,we use 2-D electrophoresis analysis,we found cystamine reduce CKMB protein performance and improvement myocardial cell damage , we investigate the myocardial cell apoptosis, survival and hypertrophy, Based on physiology data the cystamine can effectively prevent NZB/W F1 mice from hypertrophy,and we also detect with use of Western Blot analysis and 2-D electrophoresis analysis , cystamine can reduse cardiac hypertrophy performance of FABPand ANP protein, induce hypertrophy pathway,IL6 MEK5-ERK5 and p-p38, c-jun as well. In TUNEL assay it can be observed that cystamine can reduce myocardial cell apoptosis . At the same time Western Blot analysis to prove cystamine can reduce cardiac cell apoptosis and Deth receptor and Mitochondria through theses two pathsway, NF-κB protein expression significantly increased furthermore, it promots cell survival, which can reduce cardiac hypertrophy,apoptosis.

並列關鍵字

cystamine ； SLE ； heart apoptosis

參考文獻

1.Croker, J.A. and Kimberly, R.P. (2005) SLE: challenges and candidates in human disease. Trends Immunol, 26, 580-6.

2.D'Cruz, D.P., Khamashta, M.A. and Hughes, G.R. (2007) Systemic lupus erythematosus. Lancet, 369, 587-96.

3.Banchereau, J. and Pascual, V. (2006) Type I interferon in systemic lupus erythematosus and other autoimmune diseases. Immunity, 25, 383-92.

4.Tan, E.M., Cohen, A.S., Fries, J.F., Masi, A.T., McShane, D.J., Rothfield, N.F., Schaller, J.G., Talal, N. and Winchester, R.J. (1982) The 1982 revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum, 25, 1271-7.

5.Hochberg, M.C. (1997) Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum, 40, 1725.

國際替代計量

胱胺酸對狼瘡小鼠心臟凋亡之影響及相關機制探討

未授權

主題瀏覽