熊胆治疗肝脏眼睛及大脑疾病文献.doc

牛磺熊去氧胆酸在治疗肝脏和大脑疾病中的应用中磺熊去氧胆酸是亲水的胆酸，它是熊胆的主要成分，可以用來治疗胆汁分 泌异常等疾病最近报道牛磺熊去氧胆酸可以治疗肝脏疾病，抑制肝细胞毒性作 用，对抗氧化物质的产生，起到抗氧化剂的作用另外，牛磺熊去氧胆酸还可以 减轻线粒体不足及线粒体毒性作用，从而抑制细胞的凋亡在肝脏细胞中它抑制 线粒体膜病变，促进细胞色素C的释放牛磺熊去氧胆酸还能抑制祌经细胞毒性 作用，防止大脑纹状体萎缩，改善运动和感知方面的缺陷（图1，2,3）阁1左阁为末经治疗的Himtingtcm舞蹈病大鼠大脑纹状体凋亡细胞明显增多, 右图为经过治疗后纹状体凋亡细胞数量明显减少（引自Keene 2002）8 6420864la la 11 lx 1i(％)朗釤娶磊3孬2 0末治疗大鼠治疗后大以7.5图2末经治疗及经过治疗后的Himtington舞蹈病大鼠大脑纹状体凋亡细胞比值 （p<0.01）.（引自 Keene 2002）11.010.5 園 10.09.59.08.58.0图3末经治疗及经过治疗后的Huntington舞蹈病大鼠大脑纹状体体积变化 (p<0.01)•(引自 Keene 2002) 主要参考文献1. Rodrigues CM, Fan Q Wong PY，Kren BT，Steer CJ. Ursodeoxycholic acid may inhibit deoxycholic acid-induced apoptosis by modulating mitochondrial transmembrane potential and reactive oxygen species production.Mol Med. 1998 Mar;4(3): 165-78.2. Rodrigues CM，Sola S，Brito MA，Brondino CD, Brites D，Moura JJ. Amyloid beta-peptide disrupts mitochondrial membrane lipid and protein structure: protective role of tauroursodeoxycholate.Biochem Biophys Res Commun. 2001 Feb 23;281(2):468-74.3. Benz C，Angermuller S, Otto G, Sauer P, Stremmel W, Stiehl A. Effect of tauroursodeoxycholic acid on bile acid-induced apoptosis in primary human hepatocytes.Eur J Clin Invest. 2000 Mar;30(3):203-9.4. Benz C，Angermuller S, Tox U，Kloters-Plachky P，Riedel HD, Sauer P，Stremmel W，Stiehl A.Effect of tauroursodeoxycholic acid on bile-acid-induced apoptosis and cytolysis in rat hepatocytes.J Hepatol. 1998 Jan;28( 1):99-106.5. Rodrigues CM，Fan G，Ma X，Kren BT，Steer CJ. A novel role for ursodeoxycholic acid in inhibiting apoptosis by modulating mitochondrial membrane perturbation.A novel role for ursodeoxycholic acid in inhibiting apoptosis by modulating mitochondrial membrane perturbation.Rodrigues CM, Ma X，Linehan-Stieers C，Fan G, Kren BT，Steer CJ. Ursodeoxycholic acid prevents cytochrome c release in apoptosis by inhibiting mitochondrial membrane depolarization and channel formation.Cell Death Differ. 1999 Sep;6(9):842-54.6. Rodrigues CM, Stieers CL, Keene CD, Ma X, Kren BT, Low WC, Steer CJ. Tauroursodeoxycholic acid partially prevents apoptosis induced by 3-nitropropionic acid: evidence for a mitochondrial pathway independent of the permeability transition. J Neurochem. 2000 Dec;75(6):2368-79.7. Keene CD, Rodrigues CM, Eich T, Linehan-Stieers C, Abt A, Kren BT, Steer CJ, Low WC. A bile acid protects against motor and cognitive deficits and reduces striatal degeneration in the 3-nitropropionic acid model of Huntington’s disease.Exp Neurol. 2001 Oct;171(2):351-60.8. Mangiarini L, Sathasivam K, Seller M，Cozens B, Harper A, Hetherington C, Lawton M, Trottier Y, Lehrach H, Davies SW, Bates GP. Exon 1 of the HD gene with an expanded CAG repeat is sufficient to cause a progressive neurological phenotype in transgenic mice.Cell. 1996 Nov l;87(3):493-506.9. Carter RJ，Lione LA, Humby T，Mangiarini L，Mahal A，Bates GP，Dunnett SB， Morton AJ. Characterization of progressive motor deficits in mice transgenic for the human Huntington、disease mutation.J Neurosci. 1999 Apr 15; 19(8):3248-57.10. Davies SW，Turmaine M, Cozens BA, DiFiglia M, Sharp AH, Ross CA, Scherzinger E，Wanker EE，Mangiarini L，Bates GP. Formation of neuronal intranuclear inclusions underlies the neurological dysfunction in mice transgenic forthe HD mutation.Celk 1997 Aug 8;90(3):537-48-传统药典中治疗眼睛疾病的药物（牛磺 熊去氧胆酸）目的：在东方用熊胆粉治疗眼睛疾病己经有3000年的历史，但在西方的研宂中 还比较少，本实验研宄牛磺熊去氧胆酸（TUDCA）（熊胆的主要成分）在治疗视 网膜退行性病变中的作用。

方法：有两种动物视网膜退行性病变模型：基因表达的视IM膜退行性病和强光导 致视网膜退行性病分别给予牛磺熊去氧胆酸和安慰剂治疗后，进行测试视网膜 电流图和免疫组化的测定结果：牛磺熊去氧胆酸能明显减缓两组视网膜损害采用中磺熊去氧胆酸治疗后 的大鼠显示比对照组大鼠的视网膜电流图测试有较好的反应牛磺熊去氧胆酸治 疗后的视网膜外层明显老增厚，视光细胞增多并且，牛磺熊去氧胆酸治疗组大 鼠视网膜凋亡细胞明显减少结论：注射熊胆粉主要成分牛磺熊去氧胆酸能够明显抑制视光细胞的凋亡，对它 的功能和结构都起到直接保护作用这可能是在亚洲有这么久的应用熊胆粉治疗 眼睛疾病的历史的原因，而且从木研究表明此治疗方法安全、可靠50 gm图h强光导致视网膜退行性病的大鼠在应用安慰剂（左）和牛磺熊去氧胆酸（右） 治疗后视网膜结构的变化• - **Vvc*; •OSONLINL•GCLVehicleTUDCA图2:基因表达缺陷导致视网膜退行性病的大鼠在应用安慰剂（左）和牛磺熊去 氧肭酸（右）治疗后视网膜结构的变化原文：1. Boatright JII, Mori ng AG, McElroy C，et al. Tool from ancient pharmacopoeia prevents vision loss. Molecular Vision 2006; 12:1706-1714。