牛磺酸經由抑制類鐸受體訊息路徑減緩酒精誘發肝損傷之研究

Effects of Taurine Alleviates Ethanol-Mediated Liver Injury via Inhibition of TLRs Signaling

陳木林(Mu-Lin Chen)

指導教授 ： 曾博修

中山醫學大學/醫學院/生化暨生物科技研究所/碩士(2010年)

https://doi.org/10.6834/CSMU.2010.00037

摘要

過量攝取酒精會引起各種肝臟傷害，包含氧化壓力及發炎反應。牛磺酸又稱2-胺基乙磺酸，是一種大量存在於體內各器官如腦、肝、肌肉、心臟、視網膜及中樞神經系統的非必需游離胺基酸。已知牛磺酸具有許多種有益的生物功能，如抗氧化、解毒、調節神經傳導及降血脂，因此，我們想要研究牛磺酸是否能改善過量攝取酒精所誘發的肝臟損傷。我們將60隻雄性Wistar大鼠分成六組，各組飲水中分別餵食30% (w/v)葡萄糖[控制組，Glc]、20% (v/v)酒精[酒精組，Alc]、1% (w/v)牛磺酸加20% (v/v) 酒精[1%牛磺酸組，1% Tau_Alc]、2% (w/v)牛磺酸加20% (v/v)酒精[2%牛磺酸組，2% Tau_Alc]、3% (w/v)牛磺酸加20% (v/v)酒精[3%牛磺酸組，3% Tau_Alc]及20% (w/v)酒精再依每公斤體重胃管灌食25 mg silymarin [silymarin組，Sil_Alc]，連續給予四週。結果顯示，牛磺酸組的大鼠肝臟MMP9/ MMP2的活性比例及iNOS、HSP70表現量明顯比酒精組低；餵食牛磺酸的大鼠肝臟及血清中CRP的表現量也明顯低於酒精組。由DPPH自由基清除試驗、Catalase活性分析、總GSH含量及TBARs分析結果，顯示牛磺酸能緩和酒精代謝所造成之氧化壓力上升的情形。在訊息路徑方面，牛磺酸降低了酒精誘發之TLR4/5/7/9及其銜接蛋白––MyD88的表現，而其下游之MAPK (ERK1/2與P38) pathway及NF-κB的活化情形也較酒精組低。此外，牛磺酸也降低酒精誘發之PI3K/ Akt及P53/ P21 pathway的活化。牛磺酸也降低了酒精誘發之肝臟及血清中的促發炎因子TNF-α、IL-1β及 IL-6的表現量。
由這些結果，顯示牛磺酸有益於酒精造成的肝損傷，牛磺酸或許可做為保護性的補充品以避免酒精造成的肝損傷。

關鍵字

牛磺酸 ； 酒精性肝病 ； 類鐸受體

並列摘要

Excessive alcohol-intake will cause various hepatic injuries including oxidative stress and inflammation responses. Taurine, so-called 2-amino ethanesulphonic acid, is one of the most abundant non-essential free amino acids in the body distributing in brain, liver, muscle, heart, retinal and central nervous system. Since taurine is known to have various beneficial biological functions such as anti-oxidation, detoxification, regulation of neurotransduction, and reduction of serum lipid, herein we intend to investigate the effects of taurine on liver injury of rats induced by excess alcohol intake. Sixty male Wistar rats were divided into six groups and were given different water supplements for four weeks containing 30% (w/v) glucose [Control group, Glc], 20% (v/v) ethanol [Alcohol group, Alc], 1% (w/v) taurine plus 20% (v/v) ethanol [1% Taurine group, 1% Tau_Alc], 2% (w/v) taurine plus 20% (v/v) ethanol [2% Taurine group, 2% Tau_Alc], 3% (w/v) taurine plus 20% (v/v) ethanol [3% Taurine group, 3% Tau_Alc] and 20% (v/v) ethanol with intragastric fed 25 mg silymarin/ kg body weight [Silymarin group, Sil_Alc], respectively. Significant reduction of hepatic MMP-9/ MMP-2 activity ratio and the expression of iNOS and Hsp70 were observed in rats of Taurine group compared to those of Alcohol group. The level of CRP was significantly reduced in liver and serum of rats from Taurine group compared to those of Alcohol group. The results of DPPH assay, Catalase assay, total GSH assay and TBARs assay suggested that taurine attenuated the oxidative stress from alcohol metabolism. About signaling, reduction the level of TLR-4/ 5/ 7/ 9, MyD88, MAPK (ERK1/2 and P38) pathway and NF-κB were detected in livers of rats from Taurine group compared to Alcohol group. In addition, taurine reduced the alcohol-induced activation of PI3K/ Akt and P53/ P21 pathway. Also, taurine reduced the levels of proinflammatory cytokines such as TNF-α、IL-1β and IL-6 in liver and serum.
These findings revealed the beneficial effects of taurine on alcohol-mediated liver injury and suggest the potential of taurine as a protective supplement on alcohol-mediated liver injuries.

並列關鍵字

Taurine ； ALD ； TLRs

參考文獻

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