探討牛磺酸減緩狼瘡小鼠肝臟異常的相關機制

全身性紅斑性狼瘡（Systemic lupus erythematosus ; SLE）是一種慢性多系統疾病（chronic multisystem disease），可能會影響肝臟而造成傷害，而近年來，許多文獻也指出全身性紅斑性狼瘡病患的體內有過多的脂質異常現象並與狼瘡的病況有關。牛磺酸已被證實可以清除血脂、預防脂質氧化、保護因氧化而導致組織傷害的器官。所以，我們利用NZB/W F1作為實驗動物模式，探討牛磺酸在全身性紅斑性狼瘡肝臟所扮演的角色。由實驗結果發現牛磺酸確實可以降低小鼠的平均血壓、肝臟肥大、血清三酸甘油酯。利用H&E stain，發現牛磺酸可降低肝臟組織結構的損傷。利用蘇丹第三號染色，發現牛磺酸可降低脂肪滴的情況。而利用免疫組織染色法的分析，發現牛磺酸可以減少餵食高膽固醇的NZB/W F1小鼠肝臟alpha-SMA的表現。此外，利用西方墨點法發現牛磺酸可降低餵食高膽固醇狼瘡小鼠肝臟及血清C反應蛋白表現。由TUNEL assay染色法可以發現牛磺酸確實可降低由高膽固醇所造成肝臟細胞凋亡情況，並且利用西方墨點法發現牛磺酸可降低與凋亡相關的蛋白質，包括Fas、active caspase-8、Bad、bax、cytochrome c、Apaf-1的表現量以及增加Bcl-2蛋白表現量。另外在訊息傳遞分子方面，發現牛磺酸可以促進狼瘡小鼠肝臟的p-Akt、NF-kB p65、ErK1/2蛋白表現量增加，進而促進細胞存活率。此外與壓力及發炎相關的蛋白質，包括Hsp70、hsp90、Cox-2、MMP2、MMP9、iNOS的表現量在同時餵食膽固醇及牛磺酸飲食的狼瘡小鼠中也有降低情況，而與發炎及凋亡相關的p38蛋白質的表現量也有降低情況。因此我們實驗的結果證實牛磺酸可能透過降低發炎、抑制細胞凋亡，來對狼瘡小鼠NZB/W F1肝臟達到保護的作用。

關鍵字

全身性紅斑性狼瘡；牛磺酸；膽固醇；細胞凋亡

並列摘要

Systemic lupus erythematosus (SLE) is a chronic multisystem disease. Recently, various studies have indicated the increased population of liver abnormality in patients with SLE as well as the altered lipid profile characterized by increased triglycerides, low-density lipoprotein cholesterol (LDL-C) and decreased high-density lipoprotein cholesterol(HDL-C) concentrations. Taurine is known to reduce the blood lipid, lipid oxidation and prevent the oxidant-induced injury in many tissues including liver. To investigate the effect of taurine on liver of NZB/W F1 mice, we use NZB/W F1 mice as the experimental animal model. We found that average blood pressure, liver-weight, serum Triacylglycerols was significantly decreased in NZB/W F1 mice treated with taurine and cholesterol as compared to those treated with cholesterol. In H&E stain, tissues injury was significantly decreased in liver of NZB/W F1 mice treated with cholesterol and taurine as compared to those treated with cholesterol. Fat drop was significantly decreased in liver of NZB/W F1 mice treated with cholesterol and taurine as compared to those treated with cholesterol by Sudan III staining. Additionally, the alpha-SMA expression was detected by Immunohistochemistry. We found that taurine can reduce alpha-SMA expression in liver of NZB/W F1 mice fed with high cholesterol diet. As well as the C-reactive protein (CRP) that was significantly decreased in liver and serum of NZB/W F1 mice treated with cholesterol and taurine as compared to those treated with cholesterol. Additionally, we found that taurine can reduce apoptosis of liver in NZB/W F1. The pro-apoptotic protein including Fas, active caspase8, Bad, Bax, cytochrome c and Apaf-1 proteins were significantly decreased in liver of NZB/W F1 mice treated with cholesterol and taurine as compared to tose treated with cholesterol. The anti-apoptotic Bcl-2 protein was significantly increased in liver of NZB/W F1 mice treated with cholesterol and taurine as compared to those treated with cholesterol. The signal transduction protein including Erk1/2, p-Akt, NF-kB p65 protein were significantly increased in liver of NZB/W F1 mice treated with cholesterol and taurine as compared to those treated with cholesterol. In addition, we observed decreased stress and inflammation related proteins including hsp70, hsp90,MMP2, MMP9, iNOS and p38 expression in liver of NZB/W F1 mice treat with cholesterol and taurine as compared to those treated with cholesterol. Altogether, our experimental results demonstrated the aggravated effect of cholesterol and the beneficial effects of taurine on liver of NZB/W F1 mice fed with high cholesterol.

並列關鍵字

SLE ； Taurine ； cholesterol ； cell apoptosis

參考文獻

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criteria for the classification of systemic lupus erythematosus. Arthritis

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探討牛磺酸減緩狼瘡小鼠肝臟異常的相關機制

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