ABCA1和CD68在胆囊壁中的表达及意义
|
摘要
胆囊胆固醇结石病是一种常见病,多发病,其发病机制目前为止尚未完全明确,有待进一步研究探索。随着生活水平的提高,伴随脂质代谢紊乱导致的疾病增多,胆结石发病率也逐年增加。目前,胆固醇逆转运(Reverse cholesterol transport ,RCT)是一个重要的研究课题,本实验旨在通过研究脂质转运的重要调节蛋白三磷酸腺苷结合盒转运体A1(ATP binding cassette transport A1, ABCA1)和反映周围组织脂质代谢状况的巨噬细胞在胆囊壁的表达水平,探讨胆囊壁的脂质吸收转运功能和胆石病的发病机制。
目的:
1、观察ABCA1在不同胆囊病理标本中的表达和分布,探讨其与胆囊壁脂质转运的关系。
2、观察在不同胆囊病理标本中CD68阳性的巨噬细胞分布、形态、密度和排列规律,分析其在胆囊壁脂质转运中的作用。
3、比较ABCA1在胆囊胆固醇结石病人与对照组胆囊粘膜中的表达水平,分析其与胆固醇结石形成之间的关系。
4、比较CD68在胆囊胆固醇结石病人与对照组胆囊壁中的表达水平,分析其与胆固醇结石形成之间的关系。
5、比较ABCA1、CD68在胆囊胆固醇结石病人与对照组胆囊壁中的表达水平,分析ABCA1和CD68在胆囊壁脂质转运中的相关性,进一步探讨胆囊胆固醇结石的发病机制。
方法:
1、标本收集收集胆囊术后的病理标本。
1.1实验组:胆囊胆固醇结石病人34例,非结石性慢性胆囊炎合并肝胆管结石11例,胆固醇息肉8例,胆囊结石并急性胆囊炎6例。
1.2对照组:选择非胆囊结石病人胆囊标本15例,病理诊断均为正常或接近正常胆囊。
1.3所有病例均由HE染色光镜下获得病理诊断,无其他合并症及明显肝功能异常。
2、实验方法
石蜡切片脱蜡至水,采用PV-9000即用型二步法免疫组织化学染色检测ABCA1、CD68在实验组和对照组胆囊标本中的表达,ABCA1、CD68单克隆抗体的工作浓度均为1:200,以PBS代替一抗作阴性对照。
3、统计处理结果采用半定量积分法评判,数据进行统计学分析,行X2检验。
结果:
1、ABCA1的表达及分布
1.1 ABCA1主要在胆囊粘膜上皮细胞顶侧表达,上皮细胞的基底侧、粘膜下层、肌层及浆膜层无明显表达。
1.2胆囊胆固醇结石病人的胆囊粘膜ABCA1表达低于对照组胆囊粘膜的表达,两组进行半定量分析,具有统计学意义P <0.005。
1.3胆固醇息肉组、胆囊结石并急性胆囊炎组的ABCA1表达降低;与对照组比较有统计学差异。
1.4非结石性慢性胆囊炎合并肝胆管结石组的ABCA1表达升高,与对照组比较无统计学差异。
2、CD68的表达及分布
2.1 CD68主要在胆囊粘膜上皮细胞顶侧表达,胞浆着色,细胞形态为细颗粒状,呈密集分布;粘膜下层细胞大且为圆形或椭圆形,连接成片;肌层及浆膜层有散在分布,量少,细胞中等大小。
2.2胆囊胆固醇结石病人的胆囊粘膜CD68表达高于对照组胆囊粘膜的表达,两组进行半定量分析,具有统计学意义P <0.05。
2.3非结石性慢性胆囊炎合并肝胆管结石组、胆固醇息肉组CD68表达升高,与对照组比较有统计学差异。
3、ABCA1、CD68两因素间比较
3.1胆囊胆固醇结石组和胆固醇息肉组病人ABCA1表达降低,CD68表达升高,差异具有统计学意义P <0.05。
3.2非结石性慢性胆囊炎合并肝胆管结石组ABCA1、CD68阳性表达均升高,无统计学差异。
4、阴性对照无表达。
结论:
1、ABCA1、CD68主要在胆囊粘膜上皮细胞顶侧表达,说明胆囊粘膜上皮细胞具有吸收和转运脂质的功能。
2、ABCA1在胆固醇结石病人胆囊粘膜上皮细胞中表达减弱,可能在胆石病发病机制中起一定作用。
3、CD68在胆固醇结石病人胆囊粘膜上皮细胞中表达增强,与胆囊壁的脂质转运和胆结石的形成有关。
4、ABCA1与CD68在胆囊壁中的表达呈副相关性,脂质调节蛋白ABCA1功能的下降,导致胆囊壁脂质吸收和转运功能障碍,脂质沉积,诱导巨噬细胞的增加,加剧了胆汁中胆固醇的过饱和状态,促进胆固醇结石的形成。
Cholelithiasis is a familiar disease, but it’s morbidit mechanism is still not distinctive by now and needs farther study. With the development of people life level, lipid metabolism was disorganized, the incidence of cholelithiasis has been increasing every year. Now, Reverse cholesterol transport (RCT)is a question for discussion, this study is to investigate the function of the lipid absorbability and transport of gallbladder wall and the pathogenesis of cholesterol gallstone by the expression and distribution of ATP binding cassette transport A1( ABCA1) and CD68 in gallbladder wall .
Objective
1. To observe the expression and distribution of ATP binding cassette transport A1( ABCA1) in different gallbladder specimens , investigate their relationship with the lipid transport of gallbladder wall.
2. To observe the distribution, morphology ,density and array rule of CD68 positive macrophages in different gallbladder specimens, analyse its function in the lipid transport of gallbladder wall.
3. To compare betweeen the expression level of ABCA1 in the patients with cholesterol gallstone and that in controls, analyse its relationship with the formation of cholesterol gallstone.
4. To compare betweeen the expression level of CD68 in the patients with cholesterol gallstone and that in controls, analyse its relationship with the formation of cholesterol gallstone.
5. To compare betweeen the expression level of ABCA1 and CD68 in the patients with cholesterol gallstone and that in controls, analyse their relationship in the lipid transport of gallbladder wall, study the pathogenesis of cholesterol gallstone. .
Methods
1. Samples collecting gallbladder specimens after operation.
1.1 Experimental groups:the patients with cholesterol gallstone(34 cases); chronic cholecystitis without gallstone and intrahepatolithiasis (11 cases); cholesterol polypus(8 cases); acute cholecystitis(6 cases).
1.2 Control group:the specimens without cholesterol gallstone (15 cases),their pathology diagnosis were almost normal .
1.3 All cases were acquired pathology diagnosis by HE staining,without otheir disease and exceptional liver function.
2. Methods
Olefin sections were dewaxed and dehydrated, detect the expression of ABCA1 and CD68 protein in experimental groups and control group by PV-9000 two-step immunohistochemical method, the working dilution of ABCA1、CD68 mouse monoclonal antibody is 1:200, PBS is negative control instead of first antibody.
3. statistics analyse Half quantitative analysis and integral test methods; Chi-square test .
Results
1. The expression and distribution of ABCA1
1.1 ABCA1 was expressed in the apical domain of gallbladder epithelial cells,other domain was not found.
1.2 The expression of ABCA1 in gallstone patients was signigicantly decreased as compared with that in controls(P <0.005).
1.3 ABCA1 expression in the cholesterol polypus group and acute cholecystitis group was decreased as compared with that in controls ,with statistic significance(P <0.05).
1.4 ABCA1 expression in the chronic cholecystitis without gallstone and intrahepatolithiasis group was increased, without statistic significance.
2. The expression and distribution of CD68
2.1 CD68 was mostly expressed in the apical domain of gallbladder epithelial cells,other domains have staining also, the distribution, morphology ,density and array rule of macrophages have changed.
2.2 The expression of CD68 in gallstone patients was better than that in the control group, with statistic significance(P <0.05).
2.3 The expression of CD68 in the chronic cholecystitis without gallstone and intrahepatolithiasis group and the cholesterol polypus group were increased, with statistic significance.
3. The comparability between ABCA1 and CD68 protein
3.1 The expression of ABCA1 in cholesterol gallstone group and the cholesterol polypus group was decreased,while CD68 expression was increased , there were significantly difference between the two groups(P <0.05).
3.2 The expression of ABCA1 and CD68 in the chronic cholecystitis without gallstone and intrahepatolithiasis group was increased, without statistic significance.
4. The negative controls have no expression.
Conclusions
1. ABCA1 and CD68 protein was mostly expressed in the apical domain of gallbladder epithelial cells,indicating that gallbladder epithelial cells has the function to absorb and transport lipid .
2. The expression of ABCA1 protein is decreased in cholesterol gallstone patients, indicating that ABCA1 may have some effects on the pathogenesis of cholesterol gallstone.
3. The expression of CD68 protein is increased in cholesterol gallstone patients, indicating that CD68 was related with the lipid transport of gallbladder wall and the formation of cholesterol gallstone.
4. There is negative relationship between the expression of ABCA1 and CD68 in gallbladder wall ,the decrease of ABCA1 protein function in gallbladder epitheliun results in that the level of the lipid transport of gallbladder wall is declined , so lipid deposits in gallbladder wall ,and induces macrophages increasing, contributes to the super-saturation of biliary cholesterol and the formation of cholesterol gallstone . Key words:ABCA1;CD68;Macrophage;Cholesterol;Cholelithiasis;Lipid transport;Gallbladder epitheliun;Gallbladder wall;Reverse Cholesterol transport
目的:
1、观察ABCA1在不同胆囊病理标本中的表达和分布,探讨其与胆囊壁脂质转运的关系。
2、观察在不同胆囊病理标本中CD68阳性的巨噬细胞分布、形态、密度和排列规律,分析其在胆囊壁脂质转运中的作用。
3、比较ABCA1在胆囊胆固醇结石病人与对照组胆囊粘膜中的表达水平,分析其与胆固醇结石形成之间的关系。
4、比较CD68在胆囊胆固醇结石病人与对照组胆囊壁中的表达水平,分析其与胆固醇结石形成之间的关系。
5、比较ABCA1、CD68在胆囊胆固醇结石病人与对照组胆囊壁中的表达水平,分析ABCA1和CD68在胆囊壁脂质转运中的相关性,进一步探讨胆囊胆固醇结石的发病机制。
方法:
1、标本收集收集胆囊术后的病理标本。
1.1实验组:胆囊胆固醇结石病人34例,非结石性慢性胆囊炎合并肝胆管结石11例,胆固醇息肉8例,胆囊结石并急性胆囊炎6例。
1.2对照组:选择非胆囊结石病人胆囊标本15例,病理诊断均为正常或接近正常胆囊。
1.3所有病例均由HE染色光镜下获得病理诊断,无其他合并症及明显肝功能异常。
2、实验方法
石蜡切片脱蜡至水,采用PV-9000即用型二步法免疫组织化学染色检测ABCA1、CD68在实验组和对照组胆囊标本中的表达,ABCA1、CD68单克隆抗体的工作浓度均为1:200,以PBS代替一抗作阴性对照。
3、统计处理结果采用半定量积分法评判,数据进行统计学分析,行X2检验。
结果:
1、ABCA1的表达及分布
1.1 ABCA1主要在胆囊粘膜上皮细胞顶侧表达,上皮细胞的基底侧、粘膜下层、肌层及浆膜层无明显表达。
1.2胆囊胆固醇结石病人的胆囊粘膜ABCA1表达低于对照组胆囊粘膜的表达,两组进行半定量分析,具有统计学意义P <0.005。
1.3胆固醇息肉组、胆囊结石并急性胆囊炎组的ABCA1表达降低;与对照组比较有统计学差异。
1.4非结石性慢性胆囊炎合并肝胆管结石组的ABCA1表达升高,与对照组比较无统计学差异。
2、CD68的表达及分布
2.1 CD68主要在胆囊粘膜上皮细胞顶侧表达,胞浆着色,细胞形态为细颗粒状,呈密集分布;粘膜下层细胞大且为圆形或椭圆形,连接成片;肌层及浆膜层有散在分布,量少,细胞中等大小。
2.2胆囊胆固醇结石病人的胆囊粘膜CD68表达高于对照组胆囊粘膜的表达,两组进行半定量分析,具有统计学意义P <0.05。
2.3非结石性慢性胆囊炎合并肝胆管结石组、胆固醇息肉组CD68表达升高,与对照组比较有统计学差异。
3、ABCA1、CD68两因素间比较
3.1胆囊胆固醇结石组和胆固醇息肉组病人ABCA1表达降低,CD68表达升高,差异具有统计学意义P <0.05。
3.2非结石性慢性胆囊炎合并肝胆管结石组ABCA1、CD68阳性表达均升高,无统计学差异。
4、阴性对照无表达。
结论:
1、ABCA1、CD68主要在胆囊粘膜上皮细胞顶侧表达,说明胆囊粘膜上皮细胞具有吸收和转运脂质的功能。
2、ABCA1在胆固醇结石病人胆囊粘膜上皮细胞中表达减弱,可能在胆石病发病机制中起一定作用。
3、CD68在胆固醇结石病人胆囊粘膜上皮细胞中表达增强,与胆囊壁的脂质转运和胆结石的形成有关。
4、ABCA1与CD68在胆囊壁中的表达呈副相关性,脂质调节蛋白ABCA1功能的下降,导致胆囊壁脂质吸收和转运功能障碍,脂质沉积,诱导巨噬细胞的增加,加剧了胆汁中胆固醇的过饱和状态,促进胆固醇结石的形成。
Cholelithiasis is a familiar disease, but it’s morbidit mechanism is still not distinctive by now and needs farther study. With the development of people life level, lipid metabolism was disorganized, the incidence of cholelithiasis has been increasing every year. Now, Reverse cholesterol transport (RCT)is a question for discussion, this study is to investigate the function of the lipid absorbability and transport of gallbladder wall and the pathogenesis of cholesterol gallstone by the expression and distribution of ATP binding cassette transport A1( ABCA1) and CD68 in gallbladder wall .
Objective
1. To observe the expression and distribution of ATP binding cassette transport A1( ABCA1) in different gallbladder specimens , investigate their relationship with the lipid transport of gallbladder wall.
2. To observe the distribution, morphology ,density and array rule of CD68 positive macrophages in different gallbladder specimens, analyse its function in the lipid transport of gallbladder wall.
3. To compare betweeen the expression level of ABCA1 in the patients with cholesterol gallstone and that in controls, analyse its relationship with the formation of cholesterol gallstone.
4. To compare betweeen the expression level of CD68 in the patients with cholesterol gallstone and that in controls, analyse its relationship with the formation of cholesterol gallstone.
5. To compare betweeen the expression level of ABCA1 and CD68 in the patients with cholesterol gallstone and that in controls, analyse their relationship in the lipid transport of gallbladder wall, study the pathogenesis of cholesterol gallstone. .
Methods
1. Samples collecting gallbladder specimens after operation.
1.1 Experimental groups:the patients with cholesterol gallstone(34 cases); chronic cholecystitis without gallstone and intrahepatolithiasis (11 cases); cholesterol polypus(8 cases); acute cholecystitis(6 cases).
1.2 Control group:the specimens without cholesterol gallstone (15 cases),their pathology diagnosis were almost normal .
1.3 All cases were acquired pathology diagnosis by HE staining,without otheir disease and exceptional liver function.
2. Methods
Olefin sections were dewaxed and dehydrated, detect the expression of ABCA1 and CD68 protein in experimental groups and control group by PV-9000 two-step immunohistochemical method, the working dilution of ABCA1、CD68 mouse monoclonal antibody is 1:200, PBS is negative control instead of first antibody.
3. statistics analyse Half quantitative analysis and integral test methods; Chi-square test .
Results
1. The expression and distribution of ABCA1
1.1 ABCA1 was expressed in the apical domain of gallbladder epithelial cells,other domain was not found.
1.2 The expression of ABCA1 in gallstone patients was signigicantly decreased as compared with that in controls(P <0.005).
1.3 ABCA1 expression in the cholesterol polypus group and acute cholecystitis group was decreased as compared with that in controls ,with statistic significance(P <0.05).
1.4 ABCA1 expression in the chronic cholecystitis without gallstone and intrahepatolithiasis group was increased, without statistic significance.
2. The expression and distribution of CD68
2.1 CD68 was mostly expressed in the apical domain of gallbladder epithelial cells,other domains have staining also, the distribution, morphology ,density and array rule of macrophages have changed.
2.2 The expression of CD68 in gallstone patients was better than that in the control group, with statistic significance(P <0.05).
2.3 The expression of CD68 in the chronic cholecystitis without gallstone and intrahepatolithiasis group and the cholesterol polypus group were increased, with statistic significance.
3. The comparability between ABCA1 and CD68 protein
3.1 The expression of ABCA1 in cholesterol gallstone group and the cholesterol polypus group was decreased,while CD68 expression was increased , there were significantly difference between the two groups(P <0.05).
3.2 The expression of ABCA1 and CD68 in the chronic cholecystitis without gallstone and intrahepatolithiasis group was increased, without statistic significance.
4. The negative controls have no expression.
Conclusions
1. ABCA1 and CD68 protein was mostly expressed in the apical domain of gallbladder epithelial cells,indicating that gallbladder epithelial cells has the function to absorb and transport lipid .
2. The expression of ABCA1 protein is decreased in cholesterol gallstone patients, indicating that ABCA1 may have some effects on the pathogenesis of cholesterol gallstone.
3. The expression of CD68 protein is increased in cholesterol gallstone patients, indicating that CD68 was related with the lipid transport of gallbladder wall and the formation of cholesterol gallstone.
4. There is negative relationship between the expression of ABCA1 and CD68 in gallbladder wall ,the decrease of ABCA1 protein function in gallbladder epitheliun results in that the level of the lipid transport of gallbladder wall is declined , so lipid deposits in gallbladder wall ,and induces macrophages increasing, contributes to the super-saturation of biliary cholesterol and the formation of cholesterol gallstone . Key words:ABCA1;CD68;Macrophage;Cholesterol;Cholelithiasis;Lipid transport;Gallbladder epitheliun;Gallbladder wall;Reverse Cholesterol transport
引文
1. Oram JF,Lawn RM. ABCA1:the gatekeeper for eliminating excess tissue cholesterol. J Lipid Res 2001, 42: 249-257.
2. Bodzioch M, Orso E, Klucken J , et al . The gene encoding ATP-binding cassette transporter Ⅰis mutated in Tangier disease.Nat Genet, 1999, 22:347.
3. John F. Oram. Tangier disease and ABCA1.Biochimica et Biophysica Acta,2000, 1529:321-330.
4. Santamaina-fojo S, Pterson K, Knapper C,et al. Complete genomic sequence of the human ABCA1: analysis of the human and mouse ATP binding cassette promoter A. Proc Natl Acad Sci, USA, 2000,97(14):7987-7992.
5. Schmitz G, Langmann T. Structure, function, and regulation of the ABCA1 gene product[J].Curr Opin Lipidol, 2001, 12(2):129-140.
6. Langmann T, Klucken J, Reil M, et al. Molecular cloning of the human ATP binding cassette transporter Ⅰ(ABCA1): evidence for sterol dependent regulation in macrophages. Biochem Biophys Res Commun, 1999,257(1):29-33.
7. Lawn RM, Wade DP, Couse TL, et al. Localization of human ATP binding cassette transpoter Ⅰ(ABCA1) in normal and atherosclerotic tissue . Ateroscler Thromb Vasc Biol, 2001, 21(3):378-385.
8. Smith JD, Le Goff W, Settle M, et al. ABCA1 mediates concurrent cholesterol and phospholipid efflux to apolipoprotein A-I[J]. J Lipid Res, 2004, 45(4):635-644.
9. Schwart K, Lawn RM, Wade DP. ABCA1 gene expression and ApoA1 mediated cholesterol sterol efflux are regulated by LXR. Biochem Biophys Res Commun, 2000, 27493):794-802.
10. Costet P, Luo Y, Wang N, Tall AR. Sterol-dependent transactivation of the ABCA1 promotre by the liver X receptor/retinoid X receptor. J Biol Chem ,2000,274:794-802.
11. Chawla A, Boisvert WA, Lee CH, et al . A PPAR gamma-LXR- ABCA1 pathway in macrophages is involved in cholesterol efflux and atherogenesis. Mol Cell, 2001,7(1):161-171.
12. Feng B, Tabas I. ABCA1-mediated cholesterol efflux is defective in free cholesterol-loaded macrophages. Mechanism involves enhanced ABCA1 degradation in a process requiring full NPC1 activity .J Biol Chem, 2002, 277(45): 43271-43280.
13. Chao-ke TANG, Guang-hui YI,et al.Oxidized LDL upregulated ATP binding cassette tranaporter-1 in THP-1 macrophages.Acta Pharmacol Sin, 2004,25(5):581-586.
14. Nakamura K, Yasaka N, et al. Increased numbers of CD68 antigen positive dendritic epidermal cells and upregulation of CLA(cutaneous lymphocyte-associated antigen) expression on these cells in various shin diseases.J Dermatol Sci 1998 Dec,18(3):170-180.
15. 吴凡,屈伸.氧化型低密度脂蛋白对巨噬细胞 ABCA1 表达及功能的影响.华中科技大学学报,2006,35(1):14-17.
16. Chao-ke TANG, Guang-hui YI, Jun-hao YANG,et al. Oxideized LDL upregulated ATP binding cassette transporter-1 in THP-1 macrophages.Acta Pharmacol Sin, 2004,25(5):581-586.
17. 冯翔,凌文华.氧化低密度脂蛋白及溶血卵磷脂对巨噬泡沫细胞胆固醇外流的影响.中国病理生理杂志,2003,19(9):1246-1249.
18. Karen Schwartz,Richard M.Lawn, Davld P.Wade. ABCA1 gene expression and apoA-I mediated cholesterol efflux are regulated by LXR.Biochemical and biophysical research communications,2000,274:794-802.
19. Giulia Chinetti,Sophie Lestavel, Virginie Bocher,et al.PPAR-α and PPAR-γ activators induce cholesterol removal from human macrophage foam cells through stimulation of the ABCA1 pathway.Nature,2001, 7(1):53-58.
20. Astrid E.van der Velde and Albert K. Groen. Shifting gears: liver SR-BⅠ drives reverse cholesterol transport in macrophages. The Journal of Clincial Investigation,2005,115(10):2699-2701.
21. Yancey PG, Bortnick AE, Kellner-Weibel G, et al. Importance of different parthways of cellular cholesterol efflux. Arterioscler Thromb Vasc Biol, 2003, 23:712.
22. Emma I. Waddington, Emmanuel Boadu, Gordon A.Francis.Cholesterol and phospholipid efflux from cultured cells.Methods ,2005,36:196-206.
23. Yannick Hamon, Olivier Chambenoit, Giovanna Chimini. ABCA1 and the engulfmeng of apoptotic cells. Biochimica et Biophysica Acta,2002, 1585:64-71.
24. 吴在德,吴肇汉,主编. 外科学(第 6 版),人民卫生出版社,2003,558-562.
25. Lee J ,Choi HS. Reverse cholesterol transport in cultured gallbladder epithelial cells [J ]. Korean J Gastroenterol, 2004, 43(3): 145-152.
26. Koga A. Fine structure of the human gallbladder with cholesterolosis with special reference to the mechanism of lipid accumulation [J ].Br J Exp Pathol, 1985, 66(5): 605-611.
27. 许榕生。初步探讨胆囊壁内泡沫细胞及其吞脂功能在胆囊胆固醇结石形成中的作用。外科理论与实践,2005,10(4):345-348.
28. Jin LEE,Andrew SHIRK,et al. Polarized cholesterol and phospholipid efflux in cultured gall-bladder epithelial cells: evidence for an ABCA1-mediated pathway[J]. Biochem.J, 2002,364:475-484.
29. Francis M, Knopp RH, Oram,JF.Defective removal of cellular cholesterol and pholpholiphids by apolipoprotein A-I in tangier disease,Nat Genet, 1999, 22:347.
30. Knut E.Berge,Hui Tian,Gregory A.Graf,Liqing Yu,et al.Accumulation of dietary cholesterol in sitosterolemia caused by mutations in adjacent ABC transporters.Science, 2000,290(1):1771-1775.
31. 王勇,韩天权,等。胆囊粘膜 ABCG5 和 ABCG8 基因在胆固醇结石病中的作用。中华实验外科杂志,2007,24(1):51-52.
32. 蔡萌,田英.细胞 ABCA1/apoA-I 转脂途径的研究进展.美国中华临床医学杂志,2005,7(1):72-76.
33. James S. Owen, Jwen V. Mulcahy. ATP-binding A1 and HDL homeostasis. Atherosclerosis Supplements, 2002,3:13-22.
34. Ping Zheng, Andrew Horwitz, Christine A. Waelde, Jonathan D. Smith. Stably transfected ABCA1 antisense cell line has decreased ABCA1 mRAN and cAMP-induced cholesterol efflux to apolipoprotein A Ⅰ and HDL.Biochimica et Biophysica Acta, 2001,1534:121-128.
35. 唐朝克,杨永宗,等。ABCA1 在动脉粥样硬化发生与发展中的作用。生命的化学,2003,23(2):138-140.
36. 刘胜林,郭志刚,等。ABCA1 基因转录调节与胆固醇代谢及动脉粥样硬化的关系。中国分子心脏病学杂志,2004,4(5):308-311.
37. Brewer HB Jr, Santamarina-Fojo S. Clinical significance of high-density lipoproteins and the development of atherosclerosis: focus on the role of the adenosine triphosphate-binding cassette protein A1 transporter. Am J Cardiol, 2003,92(4):10-16.
38. Miquel J F,Moreno M,et al. Expression and regulation of scavenger receptor class B type Ⅰ(SR-BⅠ) in gall bladder epithelium.Gut, 2003, 52:1017-1024.
39. 李承龙,冯贤松,等。SR-BⅠ在胆固醇结石病人胆囊粘膜上皮的表达[J].腹部外科杂志,2006,19(1):55-56.
40. Kai Simons and Slina Ikonen.How cells handle cholesterol. Science. 2000,290(1):1271-1276.
41. Christopher J. Fielding, Phoebe E, Fielding. Cellular cholesterol efflux. Biochimica et Biophysica Acta, 2001,1533:175-189.
42. Corradini, S, Ripani, C,et al .The human gallbladder increases cholesterol solubility in bile by differential lipid absorption: a study using a new in vitro model of isolated intra-arterially perfused gallbladder. Hepatology, 1998, 28:314-322.
[1] 吴在德,吴肇汉,主编. 外科学(第 6 版),人民卫生出版社,2003,558-562.
[2] Lee J ,Choi HS. Reverse cholesterol transport in cultured gallbladder epithelial cells [J ]. Korean J Gastroenterol, 2004, 43(3): 145-152.
[3] Koga A. Fine structure of the human gallbladder with cholesterolosis with special reference to the mechanism of lipid accumulation [J ].Br J Exp Pathol, 1985, 66(5): 605-611.
[4] Yancey PG, Bortnick AE, Kellner-Weibel G, et al. Importance of different parthways of cellular cholesterol efflux. Arterioscler Thromb Vasc Biol, 2003, 23:712.
[5] Emma I. Waddington, Emmanuel Boadu, Gordon A.Francis.Cholesterol and phospholipid efflux from cultured cells.Methods ,2005,36:196-206.
[6] Acton S ,Rigotti A, Landschulz KT, et al .Identification of scavenger receptor SR-BⅠas a high density lipoprotein receptor[J].Science ,1996, 271(5248):15241-15248.
[7] Ueda Y,Royer L,Cong E,et al.Lower plasma levels and accelerated clearance of high density lipoprotein (HDL) and non-HDL cholesterol in scavenger receptor class B type Ⅰtransgenic mice[J].J Boil chem,1999,274(11):7165-7171.
[8] Trigatti B,Rigotti Krieger M .The role of the high density lipoprotein receptor SR-BⅠin cholesterol metabolism[J].Cuurr Opin Lipidol,2000,11(2):123-131.
[9] Miquel J F,Moreno M,et al. Expression and regulation of scavenger receptor class B type Ⅰ(SR-BⅠ) in gall bladder epithelium.Gut,2003,52:1017-1024.
[10] 李承龙,冯贤松,等。SR-BⅠ在胆固醇结石病人胆囊粘膜上皮的表达[J].腹部外科杂志,2006,19(1):55-56.
[11] Francis M, Knopp RH, Oram,JF.Defective removal of cellular cholesterol and pholpholiphids by apolipoprotein A-I in tangier disease,Nat Genet, 1999, 22:347.
[12] Oram JF, Lawn RM. ABCA1:the gatekeeper for eliminating excess tissue cholesterol. J Lipid Res, 2001, 42:1173.
[13] 唐朝克,杨永宗,等。ABCA1 在动脉粥样硬化发生与发展中的作用。生命的化学,2003,23(2):138-140.
[14] 刘胜林,郭志刚,等。ABCA1 基因转录调节与胆固醇代谢及动脉粥样硬化的关系。中国分子心脏病学杂志,2004,4(5):308-311.
[15] Jin LEE,Andrew SHIRK,et al. Polarized cholesterol and phospholipid efflux in cultured gall-bladder epithelial cells: evidence for an ABCA1-mediated pathway[J]. Biochem.J, 2002,364:475-484. 16] 王勇,韩天权,等。胆囊粘膜 ABCG5 和 ABCG8 基因在胆固醇结石病中的作用。中华实验外科杂志,2007,24(1):51-52.
[17] Chao-ke TANG, Guang-hui YI,et al.Oxidized LDL upregulated ATP binding cassettetranaporter-1 in THP-1 macrophages.Acta Pharmacol Sin, 2004,25(5):581-586.
[18] Karen Schwartz,Richard M.Lawn, Davld P.Wade. ABCA1 gene expression and apoA-I mediated cholesterol efflux are regulated by LXR.Biochemical and biophysical research communications,2000,274:794-802.
[19] 许榕生。初步探讨胆囊壁内泡沫细胞及其吞脂功能在胆囊胆固醇结石形成中的作用。外科理论与实践,2005,10(4):345-348.
[1] Oram JF, Lawn RM. ABCA1:the gatekeeper for eliminating excess tissue cholesterol. J Lipid Res, 2001, 42:1173.
[2] Bodzioch M, Orso E, Klucken J , et al . The gene encoding ATP-binding cassette transporter Ⅰis mutated in Tangier disease.Nat Genet, 1999, 22:347.
[3] Santamaina-fojo S, Pterson K, Knapper C,et al. Complete genomic sequence of the human ABCA1: analysis of the human and mouse ATP binding cassette promoter A. Proc Natl Acad Sci, USA, 2000,97(14):7987-7992.
[4] Schmitz G, Langmann T. Structure, function, and regulation of the ABCA1 gene product[J].Curr Opin Lipidol, 2001, 12(2):129-140.
[5] Smith JD, Le Goff W, Settle M, et al. ABCA1 mediates concurrent cholesterol andphospholipid efflux to apolipoprotein A-I[J]. J Lipid Res, 2004, 45(4):635-644.
[6] Langmann T, Klucken J, Reil M, et al. Molecular cloning of the human ATP binding cassette transporter Ⅰ(ABCA1): evidence for sterol dependent regulation in macrophages. Biochem Biophys Res Commun, 1999,257(1):29-33.
[7] Lawn RM, Wade DP, Couse TL, et al. Localization of human ATP binding cassette transpoter Ⅰ(ABCA1) in normal and atherosclerotic tissue . Ateroscler Thromb Vasc Biol, 2001, 21(3):378-385.
[8] Schwart K, Lawn RM, Wade DP. ABCA1 gene expression and ApoA1 mediated cholesterol sterol efflux are regulated by LXR. Biochem Biophys Res Commun, 2000, 27493):794-802.
[9] Costet P, Luo Y, Wang N, Tall AR. Sterol-dependent transactivation of the ABCA1 promotre by the liver X receptor/retinoid X receptor. J Biol Chem ,2000,274:794-802.
[10] Chawla A, Boisvert WA, Lee CH, et al . A PPAR gamma-LXR- ABCA1 pathway in macrophages is involved in cholesterol efflux and atherogenesis. Mol Cell, 2001,7(1):161-171.
[11] Feng B, Tabas I. ABCA1-mediated cholesterol efflux is defective in free cholesterol-loaded macrophages. Mechanism involves enhanced ABCA1 degradation in a process requiring full NPC1 activity .J Biol Chem, 2002, 277(45): 43271-43280.
[12] Chao-ke TANG, Guang-hui YI,et al.Oxidized LDL upregulated ATP binding cassette tranaporter-1 in THP-1 macrophages.Acta Pharmacol Sin, 2004,25(5):581-586.
[13] Koga A. Fine structure of the human gallbladder with cholesterolosis with special reference to the mechanism of lipid accumulation [J ].Br J Exp Pathol, 1985, 66(5): 605-611.
[14] Jin LEE,Andrew SHIRK,et al. Polarized cholesterol and phospholipid efflux in cultured gall-bladder epithelial cells: evidence for an ABCA1-mediated pathway[J]. Biochem.J, 2002,364:475-484.
[15] Corradini, S, Ripani, C,et al .The human gallbladder increases cholesterol solubility in bile by differential lipid absorption: a study using a new in vitro model of isolated intra-arterially perfused gallbladder. Hepatology, 1998, 28:314-322.
[16] 许榕生。初步探讨胆囊壁内泡沫细胞及其吞脂功能在胆囊胆固醇结合形成中的作用。外科理论与实践,2005,10(4):345-348.
[17] Miquel J F,Moreno M,et al. Expression and regulation of scavenger receptor class B type Ⅰ(SR-BⅠ) in gall bladder epithelium.Gut,2003,52:1017-1024.
[18] 李承龙,冯贤松,等。SR-BⅠ在胆固醇结合病人胆囊粘膜上皮的表达[J].腹部外科杂志,2006,19(1):55-56.
2. Bodzioch M, Orso E, Klucken J , et al . The gene encoding ATP-binding cassette transporter Ⅰis mutated in Tangier disease.Nat Genet, 1999, 22:347.
3. John F. Oram. Tangier disease and ABCA1.Biochimica et Biophysica Acta,2000, 1529:321-330.
4. Santamaina-fojo S, Pterson K, Knapper C,et al. Complete genomic sequence of the human ABCA1: analysis of the human and mouse ATP binding cassette promoter A. Proc Natl Acad Sci, USA, 2000,97(14):7987-7992.
5. Schmitz G, Langmann T. Structure, function, and regulation of the ABCA1 gene product[J].Curr Opin Lipidol, 2001, 12(2):129-140.
6. Langmann T, Klucken J, Reil M, et al. Molecular cloning of the human ATP binding cassette transporter Ⅰ(ABCA1): evidence for sterol dependent regulation in macrophages. Biochem Biophys Res Commun, 1999,257(1):29-33.
7. Lawn RM, Wade DP, Couse TL, et al. Localization of human ATP binding cassette transpoter Ⅰ(ABCA1) in normal and atherosclerotic tissue . Ateroscler Thromb Vasc Biol, 2001, 21(3):378-385.
8. Smith JD, Le Goff W, Settle M, et al. ABCA1 mediates concurrent cholesterol and phospholipid efflux to apolipoprotein A-I[J]. J Lipid Res, 2004, 45(4):635-644.
9. Schwart K, Lawn RM, Wade DP. ABCA1 gene expression and ApoA1 mediated cholesterol sterol efflux are regulated by LXR. Biochem Biophys Res Commun, 2000, 27493):794-802.
10. Costet P, Luo Y, Wang N, Tall AR. Sterol-dependent transactivation of the ABCA1 promotre by the liver X receptor/retinoid X receptor. J Biol Chem ,2000,274:794-802.
11. Chawla A, Boisvert WA, Lee CH, et al . A PPAR gamma-LXR- ABCA1 pathway in macrophages is involved in cholesterol efflux and atherogenesis. Mol Cell, 2001,7(1):161-171.
12. Feng B, Tabas I. ABCA1-mediated cholesterol efflux is defective in free cholesterol-loaded macrophages. Mechanism involves enhanced ABCA1 degradation in a process requiring full NPC1 activity .J Biol Chem, 2002, 277(45): 43271-43280.
13. Chao-ke TANG, Guang-hui YI,et al.Oxidized LDL upregulated ATP binding cassette tranaporter-1 in THP-1 macrophages.Acta Pharmacol Sin, 2004,25(5):581-586.
14. Nakamura K, Yasaka N, et al. Increased numbers of CD68 antigen positive dendritic epidermal cells and upregulation of CLA(cutaneous lymphocyte-associated antigen) expression on these cells in various shin diseases.J Dermatol Sci 1998 Dec,18(3):170-180.
15. 吴凡,屈伸.氧化型低密度脂蛋白对巨噬细胞 ABCA1 表达及功能的影响.华中科技大学学报,2006,35(1):14-17.
16. Chao-ke TANG, Guang-hui YI, Jun-hao YANG,et al. Oxideized LDL upregulated ATP binding cassette transporter-1 in THP-1 macrophages.Acta Pharmacol Sin, 2004,25(5):581-586.
17. 冯翔,凌文华.氧化低密度脂蛋白及溶血卵磷脂对巨噬泡沫细胞胆固醇外流的影响.中国病理生理杂志,2003,19(9):1246-1249.
18. Karen Schwartz,Richard M.Lawn, Davld P.Wade. ABCA1 gene expression and apoA-I mediated cholesterol efflux are regulated by LXR.Biochemical and biophysical research communications,2000,274:794-802.
19. Giulia Chinetti,Sophie Lestavel, Virginie Bocher,et al.PPAR-α and PPAR-γ activators induce cholesterol removal from human macrophage foam cells through stimulation of the ABCA1 pathway.Nature,2001, 7(1):53-58.
20. Astrid E.van der Velde and Albert K. Groen. Shifting gears: liver SR-BⅠ drives reverse cholesterol transport in macrophages. The Journal of Clincial Investigation,2005,115(10):2699-2701.
21. Yancey PG, Bortnick AE, Kellner-Weibel G, et al. Importance of different parthways of cellular cholesterol efflux. Arterioscler Thromb Vasc Biol, 2003, 23:712.
22. Emma I. Waddington, Emmanuel Boadu, Gordon A.Francis.Cholesterol and phospholipid efflux from cultured cells.Methods ,2005,36:196-206.
23. Yannick Hamon, Olivier Chambenoit, Giovanna Chimini. ABCA1 and the engulfmeng of apoptotic cells. Biochimica et Biophysica Acta,2002, 1585:64-71.
24. 吴在德,吴肇汉,主编. 外科学(第 6 版),人民卫生出版社,2003,558-562.
25. Lee J ,Choi HS. Reverse cholesterol transport in cultured gallbladder epithelial cells [J ]. Korean J Gastroenterol, 2004, 43(3): 145-152.
26. Koga A. Fine structure of the human gallbladder with cholesterolosis with special reference to the mechanism of lipid accumulation [J ].Br J Exp Pathol, 1985, 66(5): 605-611.
27. 许榕生。初步探讨胆囊壁内泡沫细胞及其吞脂功能在胆囊胆固醇结石形成中的作用。外科理论与实践,2005,10(4):345-348.
28. Jin LEE,Andrew SHIRK,et al. Polarized cholesterol and phospholipid efflux in cultured gall-bladder epithelial cells: evidence for an ABCA1-mediated pathway[J]. Biochem.J, 2002,364:475-484.
29. Francis M, Knopp RH, Oram,JF.Defective removal of cellular cholesterol and pholpholiphids by apolipoprotein A-I in tangier disease,Nat Genet, 1999, 22:347.
30. Knut E.Berge,Hui Tian,Gregory A.Graf,Liqing Yu,et al.Accumulation of dietary cholesterol in sitosterolemia caused by mutations in adjacent ABC transporters.Science, 2000,290(1):1771-1775.
31. 王勇,韩天权,等。胆囊粘膜 ABCG5 和 ABCG8 基因在胆固醇结石病中的作用。中华实验外科杂志,2007,24(1):51-52.
32. 蔡萌,田英.细胞 ABCA1/apoA-I 转脂途径的研究进展.美国中华临床医学杂志,2005,7(1):72-76.
33. James S. Owen, Jwen V. Mulcahy. ATP-binding A1 and HDL homeostasis. Atherosclerosis Supplements, 2002,3:13-22.
34. Ping Zheng, Andrew Horwitz, Christine A. Waelde, Jonathan D. Smith. Stably transfected ABCA1 antisense cell line has decreased ABCA1 mRAN and cAMP-induced cholesterol efflux to apolipoprotein A Ⅰ and HDL.Biochimica et Biophysica Acta, 2001,1534:121-128.
35. 唐朝克,杨永宗,等。ABCA1 在动脉粥样硬化发生与发展中的作用。生命的化学,2003,23(2):138-140.
36. 刘胜林,郭志刚,等。ABCA1 基因转录调节与胆固醇代谢及动脉粥样硬化的关系。中国分子心脏病学杂志,2004,4(5):308-311.
37. Brewer HB Jr, Santamarina-Fojo S. Clinical significance of high-density lipoproteins and the development of atherosclerosis: focus on the role of the adenosine triphosphate-binding cassette protein A1 transporter. Am J Cardiol, 2003,92(4):10-16.
38. Miquel J F,Moreno M,et al. Expression and regulation of scavenger receptor class B type Ⅰ(SR-BⅠ) in gall bladder epithelium.Gut, 2003, 52:1017-1024.
39. 李承龙,冯贤松,等。SR-BⅠ在胆固醇结石病人胆囊粘膜上皮的表达[J].腹部外科杂志,2006,19(1):55-56.
40. Kai Simons and Slina Ikonen.How cells handle cholesterol. Science. 2000,290(1):1271-1276.
41. Christopher J. Fielding, Phoebe E, Fielding. Cellular cholesterol efflux. Biochimica et Biophysica Acta, 2001,1533:175-189.
42. Corradini, S, Ripani, C,et al .The human gallbladder increases cholesterol solubility in bile by differential lipid absorption: a study using a new in vitro model of isolated intra-arterially perfused gallbladder. Hepatology, 1998, 28:314-322.
[1] 吴在德,吴肇汉,主编. 外科学(第 6 版),人民卫生出版社,2003,558-562.
[2] Lee J ,Choi HS. Reverse cholesterol transport in cultured gallbladder epithelial cells [J ]. Korean J Gastroenterol, 2004, 43(3): 145-152.
[3] Koga A. Fine structure of the human gallbladder with cholesterolosis with special reference to the mechanism of lipid accumulation [J ].Br J Exp Pathol, 1985, 66(5): 605-611.
[4] Yancey PG, Bortnick AE, Kellner-Weibel G, et al. Importance of different parthways of cellular cholesterol efflux. Arterioscler Thromb Vasc Biol, 2003, 23:712.
[5] Emma I. Waddington, Emmanuel Boadu, Gordon A.Francis.Cholesterol and phospholipid efflux from cultured cells.Methods ,2005,36:196-206.
[6] Acton S ,Rigotti A, Landschulz KT, et al .Identification of scavenger receptor SR-BⅠas a high density lipoprotein receptor[J].Science ,1996, 271(5248):15241-15248.
[7] Ueda Y,Royer L,Cong E,et al.Lower plasma levels and accelerated clearance of high density lipoprotein (HDL) and non-HDL cholesterol in scavenger receptor class B type Ⅰtransgenic mice[J].J Boil chem,1999,274(11):7165-7171.
[8] Trigatti B,Rigotti Krieger M .The role of the high density lipoprotein receptor SR-BⅠin cholesterol metabolism[J].Cuurr Opin Lipidol,2000,11(2):123-131.
[9] Miquel J F,Moreno M,et al. Expression and regulation of scavenger receptor class B type Ⅰ(SR-BⅠ) in gall bladder epithelium.Gut,2003,52:1017-1024.
[10] 李承龙,冯贤松,等。SR-BⅠ在胆固醇结石病人胆囊粘膜上皮的表达[J].腹部外科杂志,2006,19(1):55-56.
[11] Francis M, Knopp RH, Oram,JF.Defective removal of cellular cholesterol and pholpholiphids by apolipoprotein A-I in tangier disease,Nat Genet, 1999, 22:347.
[12] Oram JF, Lawn RM. ABCA1:the gatekeeper for eliminating excess tissue cholesterol. J Lipid Res, 2001, 42:1173.
[13] 唐朝克,杨永宗,等。ABCA1 在动脉粥样硬化发生与发展中的作用。生命的化学,2003,23(2):138-140.
[14] 刘胜林,郭志刚,等。ABCA1 基因转录调节与胆固醇代谢及动脉粥样硬化的关系。中国分子心脏病学杂志,2004,4(5):308-311.
[15] Jin LEE,Andrew SHIRK,et al. Polarized cholesterol and phospholipid efflux in cultured gall-bladder epithelial cells: evidence for an ABCA1-mediated pathway[J]. Biochem.J, 2002,364:475-484. 16] 王勇,韩天权,等。胆囊粘膜 ABCG5 和 ABCG8 基因在胆固醇结石病中的作用。中华实验外科杂志,2007,24(1):51-52.
[17] Chao-ke TANG, Guang-hui YI,et al.Oxidized LDL upregulated ATP binding cassettetranaporter-1 in THP-1 macrophages.Acta Pharmacol Sin, 2004,25(5):581-586.
[18] Karen Schwartz,Richard M.Lawn, Davld P.Wade. ABCA1 gene expression and apoA-I mediated cholesterol efflux are regulated by LXR.Biochemical and biophysical research communications,2000,274:794-802.
[19] 许榕生。初步探讨胆囊壁内泡沫细胞及其吞脂功能在胆囊胆固醇结石形成中的作用。外科理论与实践,2005,10(4):345-348.
[1] Oram JF, Lawn RM. ABCA1:the gatekeeper for eliminating excess tissue cholesterol. J Lipid Res, 2001, 42:1173.
[2] Bodzioch M, Orso E, Klucken J , et al . The gene encoding ATP-binding cassette transporter Ⅰis mutated in Tangier disease.Nat Genet, 1999, 22:347.
[3] Santamaina-fojo S, Pterson K, Knapper C,et al. Complete genomic sequence of the human ABCA1: analysis of the human and mouse ATP binding cassette promoter A. Proc Natl Acad Sci, USA, 2000,97(14):7987-7992.
[4] Schmitz G, Langmann T. Structure, function, and regulation of the ABCA1 gene product[J].Curr Opin Lipidol, 2001, 12(2):129-140.
[5] Smith JD, Le Goff W, Settle M, et al. ABCA1 mediates concurrent cholesterol andphospholipid efflux to apolipoprotein A-I[J]. J Lipid Res, 2004, 45(4):635-644.
[6] Langmann T, Klucken J, Reil M, et al. Molecular cloning of the human ATP binding cassette transporter Ⅰ(ABCA1): evidence for sterol dependent regulation in macrophages. Biochem Biophys Res Commun, 1999,257(1):29-33.
[7] Lawn RM, Wade DP, Couse TL, et al. Localization of human ATP binding cassette transpoter Ⅰ(ABCA1) in normal and atherosclerotic tissue . Ateroscler Thromb Vasc Biol, 2001, 21(3):378-385.
[8] Schwart K, Lawn RM, Wade DP. ABCA1 gene expression and ApoA1 mediated cholesterol sterol efflux are regulated by LXR. Biochem Biophys Res Commun, 2000, 27493):794-802.
[9] Costet P, Luo Y, Wang N, Tall AR. Sterol-dependent transactivation of the ABCA1 promotre by the liver X receptor/retinoid X receptor. J Biol Chem ,2000,274:794-802.
[10] Chawla A, Boisvert WA, Lee CH, et al . A PPAR gamma-LXR- ABCA1 pathway in macrophages is involved in cholesterol efflux and atherogenesis. Mol Cell, 2001,7(1):161-171.
[11] Feng B, Tabas I. ABCA1-mediated cholesterol efflux is defective in free cholesterol-loaded macrophages. Mechanism involves enhanced ABCA1 degradation in a process requiring full NPC1 activity .J Biol Chem, 2002, 277(45): 43271-43280.
[12] Chao-ke TANG, Guang-hui YI,et al.Oxidized LDL upregulated ATP binding cassette tranaporter-1 in THP-1 macrophages.Acta Pharmacol Sin, 2004,25(5):581-586.
[13] Koga A. Fine structure of the human gallbladder with cholesterolosis with special reference to the mechanism of lipid accumulation [J ].Br J Exp Pathol, 1985, 66(5): 605-611.
[14] Jin LEE,Andrew SHIRK,et al. Polarized cholesterol and phospholipid efflux in cultured gall-bladder epithelial cells: evidence for an ABCA1-mediated pathway[J]. Biochem.J, 2002,364:475-484.
[15] Corradini, S, Ripani, C,et al .The human gallbladder increases cholesterol solubility in bile by differential lipid absorption: a study using a new in vitro model of isolated intra-arterially perfused gallbladder. Hepatology, 1998, 28:314-322.
[16] 许榕生。初步探讨胆囊壁内泡沫细胞及其吞脂功能在胆囊胆固醇结合形成中的作用。外科理论与实践,2005,10(4):345-348.
[17] Miquel J F,Moreno M,et al. Expression and regulation of scavenger receptor class B type Ⅰ(SR-BⅠ) in gall bladder epithelium.Gut,2003,52:1017-1024.
[18] 李承龙,冯贤松,等。SR-BⅠ在胆固醇结合病人胆囊粘膜上皮的表达[J].腹部外科杂志,2006,19(1):55-56.