膽固醇結石患者肝臟核受體基因表達的研究_《中國普外基礎與臨床雜志》

作者：

楊士勇 ¹ , 王建承 ² , 韓天權 ² , 王小平 ¹ , 蔡劬 ² , 姜志宏 ² , 蔣兆彥 ² , 蔡杏興 ² , 張圣道 ²

1.南京醫科大學附屬南京第一醫院普外科(南京210006);;
2.上海交通大學醫學院附屬瑞金醫院外科，上海消化外科研究所（上海200025）;

關鍵詞：

膽固醇結石病肝受體同類物1 基因表達

視頻：

導出 下載 收藏 掃碼 引用

摘要 全文 圖表 視頻 參考文獻 施引文獻 補充材料

目的　研究膽囊膽固醇結石患者肝臟的核受體基因：肝臟X受體α (liver X receptor α，LXRα)、法尼醇受體(farnesoid X receptor,FXR)、人類固醇異生物受體(steroid xenobiotic receptor,SXR)及肝受體同類物1(liver receptor homolog 1，LRH-1)的表達，探討膽固醇結石病的發病機理。
方法　27例膽囊膽固醇結石患者(膽石組)，男6例，女21例，平均年齡(52.44±1.92)歲。10例無膽石癥的膽囊息肉患者為對照(對照組)，男6例，女4例，平均年齡(47.10±2.73)歲。測定膽石膽固醇成分及血清脂類成分：總膽固醇(TC)、甘油三酯(TG)、高密度脂蛋白膽固醇(HDL-ch)、載脂蛋白(Apo)B和ApoA1和膽汁脂類成分(膽固醇、磷脂和膽汁酸)，并計算膽汁總脂和膽汁膽固醇飽和指數。實時定量PCR法測定肝臟LRH-1、FXR、SXR及LXRα基因的表達量。
結果　膽石組血清中HDL-ch濃度明顯低于對照組〔(0.93±0.05) mmol/L vs (1.33±0.09) mmol/L〕, P＜0.001; ApoA1濃度也低于對照組〔(1.19±0.05) g/L vs (1.36±0.06) g/L〕, P＜0.05; 血清ApoB、TC和TG 2組比較差異均無統計學意義(P gt;0.05)。膽石組膽汁呈膽固醇過飽和(膽固醇過飽和指數： 1.17±0.02 vs 0.79±0.10, P＜0.001)；膽汁膽固醇摩爾百分比濃度較對照組升高〔(7.96±0.39) mol〖WTB4〗%〖WTBZ〗 vs (5.26±0.89) mol%〕，P＜0.01；膽汁總脂較對照組明顯下降〔(104.72±10.51) g/L vs (154.24±14.20) g/L〕, P＜0.05；膽汁中膽汁酸和磷脂成分2組比較差異均無統計學意義(P gt;0.05)。膽石組LRH-1表達高于對照組(14.18±1.80 vs 7.22±2.22)，P＜0.05，LXRα、FXR和SXR表達2組差異無統計學意義(P gt;0.05)。
結論　人類肝臟LRH-1的表達增高與膽囊膽固醇結石形成有關。

引用本文： 楊士勇,王建承,韓天權,王小平,蔡劬,姜志宏,蔣兆彥,蔡杏興,張圣道. 膽固醇結石患者肝臟核受體基因表達的研究. 中國普外基礎與臨床雜志, 2008, 15(10): 751-755. doi: 復制

1.	McKenna NJ, O’Malley BW. Combinatorial control of gene expression by nuclear receptors and coregulators [Ｊ]. Cell, 2002; 108(4)∶465.
2.	Lammert F, Carey MC, Paigen B. Chromosomal organization of candidate genes involved in cholesterol gallstone formation： a murine gallstone map [Ｊ]. Gastroenterology, 2001; 120(1)∶221.
3.	Fayard E, Auwerx J, Schoonjans K. LRH-1: an orphan nuclear receptor involved in development, metabolism and steroidogenesis [Ｊ]. Trends Cell Biol, 2004; 14(5)∶250.
4.	Eloranta JJ, Kullak-Ublick GA. Coordinate transcriptional regulation of bile acid homeostasis and drug metabolism [Ｊ]. Arch Biochem Biophys, 2005; 433(2)∶397.
5.	Liu Y, Binz J, Numerick MJ, et al. Hepatoprotection by the farnesoid X receptor agonist GW4064 in rat models of intra- and extrahepatic cholestasis [Ｊ]. J Clin Invest, 2003; 112(11)∶16786　Wang DQ, Afdhal NH. Genetic analysis of cholesterol gallstone formation： searching for Lith (gallstone) genes [Ｊ]. Curr Gastroenterol Rep, 2004; 6(2)∶140.
6.	孔凡民，隋春陽，李航宇，等. 膽囊膽固醇結石與肝細胞膽管膜上轉運子BSEP、MRP2和MDR3關系的研究 [Ｊ]. 中國普外基礎與臨床雜志, 2006; 13(3)∶314.
7.	劉君，龍厚勇，明晗昕，等. 肝細胞MDR1基因表達與膽囊膽固醇結石相關性研究 [Ｊ]. 中國普外基礎與臨床雜志, 2005; 12(4)∶346.
8.	湯文浩, 韓天權, 張圣道. 測定膽汁膽固醇和磷脂的簡捷方法 [Ｊ]. 上海醫學檢驗雜志, 1994; 9(2)∶122.
9.	Carey MC. Critical tables for calculating the cholesterol saturation of native bile [Ｊ]. J Lipid Res, 1978; 19(8)∶945.
10.	傅培彬，張圣道，戴坤揚，等. 以膽石剖面結構及化學成分為基礎的膽石分類法 [Ｊ]. 中華外科雜志, 1984, 22(4)∶258.
11.	Escriva H, Delaunay F, Laudet V. Ligand binding and nuclear receptor evolution [Ｊ]. Bioessays, 2000; 22(8)∶717.
12.	Moschetta A, Bookout AL, Mangelsdorf DJ. Prevention of cholesterol gallstone disease by FXR agonists in a mouse model [Ｊ]. Nat Med, 2004; 10(12)∶1352.
13.	Kosters A, Jirsa M, Groen AK. Genetic background of cholesterol gallstone disease [Ｊ]. Biochim Biophys Acta, 2003; 1637(1)∶1.
14.	Moschetta A, vanBerge-Henegouwen GP, Portincasa P, et al. Cholesterol crystallization in model biles： effects of bile salt and phospholipid species composition [Ｊ]. J Lipid Res, 2001; 42(8)∶1273.
15.	蔣兆彥，韓天權，所廣軍，等. 膽固醇結石病人肝臟膽小管側膜ATP基因表達差異的研究 [Ｊ]. 外科理論與實踐, 2005; 10(1)∶61.
16.	Bertolotti M, Gabbi C, Anzivino C, et al. Decreased hepatic expression of PPAR-gamma coactivator-1 in cholesterol cholelithiasis [Ｊ]. Eur J Clin Invest, 2006; 36(3)∶170.
17.	Staudinger JL, Goodwin B, Jones SA, et al. The nuclear receptor PXR is a lithocholic acid sensor that protects against liver toxicity [Ｊ]. Proc Natl Acad Sci USA, 2001; 98(6)∶3369.
18.	Schoonjans K, Annicotte JS, Huby T, et al. Liver receptor homolog 1 controls the expression of the scavenger receptor class B type Ⅰ [Ｊ]. EMBO Rep, 2002; 3(12)∶1181.
19.	Freeman LA, Kennedy A, Wu J, et al. The orphan nuclear receptor LRH-1 activates the ABCG5/ABCG8 intergenic promoter [Ｊ]. J Lipid Res, 2004; 45(7)∶1197.
20.	Luo Y, Liang CP, Tall AR. The orphan nuclear receptor LRH-1 potentiates the sterol-mediated induction of the human CETP gene by liver X receptor [Ｊ]. J Biol Chem, 2001; 276(27)∶24767.

1. 　McKenna NJ, O’Malley BW. Combinatorial control of gene expression by nuclear receptors and coregulators [Ｊ]. Cell, 2002; 108(4)∶465.
2. 　Lammert F, Carey MC, Paigen B. Chromosomal organization of candidate genes involved in cholesterol gallstone formation： a murine gallstone map [Ｊ]. Gastroenterology, 2001; 120(1)∶221.
3. 　Fayard E, Auwerx J, Schoonjans K. LRH-1: an orphan nuclear receptor involved in development, metabolism and steroidogenesis [Ｊ]. Trends Cell Biol, 2004; 14(5)∶250.
4. 　Eloranta JJ, Kullak-Ublick GA. Coordinate transcriptional regulation of bile acid homeostasis and drug metabolism [Ｊ]. Arch Biochem Biophys, 2005; 433(2)∶397.
5. 　Liu Y, Binz J, Numerick MJ, et al. Hepatoprotection by the farnesoid X receptor agonist GW4064 in rat models of intra- and extrahepatic cholestasis [Ｊ]. J Clin Invest, 2003; 112(11)∶16786　Wang DQ, Afdhal NH. Genetic analysis of cholesterol gallstone formation： searching for Lith (gallstone) genes [Ｊ]. Curr Gastroenterol Rep, 2004; 6(2)∶140.
6. 　孔凡民，隋春陽，李航宇，等. 膽囊膽固醇結石與肝細胞膽管膜上轉運子BSEP、MRP2和MDR3關系的研究 [Ｊ]. 中國普外基礎與臨床雜志, 2006; 13(3)∶314.
7. 　劉君，龍厚勇，明晗昕，等. 肝細胞MDR1基因表達與膽囊膽固醇結石相關性研究 [Ｊ]. 中國普外基礎與臨床雜志, 2005; 12(4)∶346.
8. 　湯文浩, 韓天權, 張圣道. 測定膽汁膽固醇和磷脂的簡捷方法 [Ｊ]. 上海醫學檢驗雜志, 1994; 9(2)∶122.
9. 　Carey MC. Critical tables for calculating the cholesterol saturation of native bile [Ｊ]. J Lipid Res, 1978; 19(8)∶945.
10. 　傅培彬，張圣道，戴坤揚，等. 以膽石剖面結構及化學成分為基礎的膽石分類法 [Ｊ]. 中華外科雜志, 1984, 22(4)∶258.
11. 　Escriva H, Delaunay F, Laudet V. Ligand binding and nuclear receptor evolution [Ｊ]. Bioessays, 2000; 22(8)∶717.
12. 　Moschetta A, Bookout AL, Mangelsdorf DJ. Prevention of cholesterol gallstone disease by FXR agonists in a mouse model [Ｊ]. Nat Med, 2004; 10(12)∶1352.
13. 　Kosters A, Jirsa M, Groen AK. Genetic background of cholesterol gallstone disease [Ｊ]. Biochim Biophys Acta, 2003; 1637(1)∶1.
14. 　Moschetta A, vanBerge-Henegouwen GP, Portincasa P, et al. Cholesterol crystallization in model biles： effects of bile salt and phospholipid species composition [Ｊ]. J Lipid Res, 2001; 42(8)∶1273.
15. 　蔣兆彥，韓天權，所廣軍，等. 膽固醇結石病人肝臟膽小管側膜ATP基因表達差異的研究 [Ｊ]. 外科理論與實踐, 2005; 10(1)∶61.
16. 　Bertolotti M, Gabbi C, Anzivino C, et al. Decreased hepatic expression of PPAR-gamma coactivator-1 in cholesterol cholelithiasis [Ｊ]. Eur J Clin Invest, 2006; 36(3)∶170.
17. 　Staudinger JL, Goodwin B, Jones SA, et al. The nuclear receptor PXR is a lithocholic acid sensor that protects against liver toxicity [Ｊ]. Proc Natl Acad Sci USA, 2001; 98(6)∶3369.
18. 　Schoonjans K, Annicotte JS, Huby T, et al. Liver receptor homolog 1 controls the expression of the scavenger receptor class B type Ⅰ [Ｊ]. EMBO Rep, 2002; 3(12)∶1181.
19. 　Freeman LA, Kennedy A, Wu J, et al. The orphan nuclear receptor LRH-1 activates the ABCG5/ABCG8 intergenic promoter [Ｊ]. J Lipid Res, 2004; 45(7)∶1197.
20. 　Luo Y, Liang CP, Tall AR. The orphan nuclear receptor LRH-1 potentiates the sterol-mediated induction of the human CETP gene by liver X receptor [Ｊ]. J Biol Chem, 2001; 276(27)∶24767.

《中國普外基礎與臨床雜志》

膽固醇結石患者肝臟核受體基因表達的研究

摘要 全文 圖表 視頻 參考文獻 施引文獻 補充材料

Format

Content

《中國普外基礎與臨床雜志》

膽固醇結石患者肝臟核受體基因表達的研究

摘要 全文 圖表 視頻 參考文獻 施引文獻 補充材料

Format

Content

摘要全文圖表視頻參考文獻施引文獻補充材料