女性激素在膽囊膽固醇結石形成中的作用的研究現狀_《中國普外基礎與臨床雜志》

作者：

聶云貴 , 丁佑銘 , 汪斌

武漢大學人民醫院肝膽腔鏡外科（湖北武漢 430060）;

關鍵詞：

雌激素孕酮膽囊膽固醇結石

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　綜述女性激素致膽囊膽固醇結石形成的機制，為預防雌、孕激素致石形成尋找途徑。
方法　復習有關雌、孕激素致石形成的文獻，總結其致石機制。
結果　雌激素主要通過核效應機制影響膽固醇代謝導致膽固醇結石形成，也可通過非核效應促使膽固醇成核及影響膽汁排空參與結石形成。孕激素通過核效應機制影響介導膽囊平滑肌收縮舒張的G蛋白α亞基損傷膽囊運動，通過非核效應途徑影響離子通道及信號傳導削弱膽囊運動，但孕酮的非核效應在結石形成中可能不起重要作用。
結論　女性激素致石機制復雜，明確其相關致石機制可為預防雌、孕激素致石形成開辟新途徑。

引用本文： 聶云貴,丁佑銘,汪斌. 女性激素在膽囊膽固醇結石形成中的作用的研究現狀. 中國普外基礎與臨床雜志, 2012, 19(8): 904-910. doi: 復制

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1. Novacek G. Gender and gallstone disease[J]. Wien Med Wochenschr， 2006， 156(19-20)：527-533.
2. Bolukbas FF， Bolukbas C， Horoz M， et al. Risk factors associated with gallstone and biliary sludge formation during pregnancy[J]. J Gastroenterol Hepatol， 2006， 21(7)：1150-1153.
3. Shaffer EA. Gallstone disease：Epidemiology of gallbladder stone disease[J]. Best Pract Res Clin Gastroenterol， 2006， 20(6)：981-996.
4. Wang DQ， Afdhal NH. Genetic analysis of cholesterol gallstone formation：searching for Lith (gallstone) genes[J]. Curr Gastroenterol Rep， 2004， 6(2)：140-150.
5. Uhler ML，Marks JW， Voigt BJ， et al. Comparison of the impact of transdermal versus oral estrogens on biliary markers of gallstone formation in postmenopausal women[J]. J Clin Endocrinol Metab， 1998， 83(2)：410-414.
6. Wang HH， Afdhal NH， Wang DQ. Estrogen receptor alpha， but not beta， plays a major role in 17beta-estradiol-induced murine cholesterol gallstones[J]. Gastroenterology， 2004， 127(1)：239-249.
7. Wang HH， Afdhal NH， Wang DQ. Overexpression of estrogen receptor alpha increases hepatic cholesterogenesis， leading to biliary hypersecretion in mice[J]. J Lipid Res， 2006， 47(4)：778-786.
8. Ohashi A， Wang DQ. 17β-estradiol increases cholesterol cholelithogenesis in gallstone-resistant mice through mediating the expression of hepatic lipid transporters (Abstract)[J]. Gastroenterology， 2002， 122：A7.
9. Wang HH， Afdhal NH， Wang DQ. The blockade of estrogen action by fulvestrant (ICI 182， 780) prevents cholesterol gallstone formation in the mouse (abstr)[J]. Hepatology， 2003， 38(4)：195A.
10. Everson GT， McKinley C， Kern F Jr. Mechanisms of gallstone formation in women. Effects of exogenous estrogen (Premarin) and dietary cholesterol on hepatic lipid metabolism[J]. J Clin Invest， 1991， 87(1)：237-246.
11. Coyne MJ， Bonorris GG， Chung A， et al. Estrogen enhances dietary cholesterol induction of saturated bile in the hamster[J]. Gastroenterology， 1978， 75(1)：76-79.
12. Kuiper GG， Carlsson B， Grandien K， et al. Comparison of the ligand binding specificity and transcript tissue distribution of estrogen receptors alpha and beta[J]. Endocrinology， 1997， 138(3)：863-870.
13. Yu L， Li-Hawkins J， Hammer RE， et al. Overexpression of ABCG5 and ABCG8 promotes biliary cholesterol secretion and reduces fractional absorption of dietary cholesterol[J]. J Clin Invest， 2002， 110(5)：671-680.
14. Repa JJ， Berge KE， Pomajzl C， et al. Regulation of ATP-binding cassette sterol transporters ABCG5 and ABCG8 by the liver X receptors alpha and beta[J]. J Biol Chem，2002， 277(21)：18793-18800.
15. Yu L， York J， von Bergmann K， et al. Stimulation of cholesterol excretion by the liver X receptor agonist requires ATP-binding cassette transporters G5 and G8[J]. J Biol Chem， 2003， 278(18)：15565-15570.
16. Jiang ZY， Parini P， Eggertsen G， et al. Increased expression of LXR alpha， ABCG5， ABCG8， and SR-BI in the liver from normolipidemic， nonobese Chinese gallstone patients[J]. J Lipid Res， 2008， 49(2)：464-472.
17. Cui W， Jiang ZY， Cai Q， et al. Decreased NPC1L1 expression in the liver from Chinese female gallstone patients[J]. Lipids Health Dis， 2010， 9：17.
18. Baskaran V， Vij U， Sahni P， et al. Do the progesterone receptors have a role to play in gallbladder cancer?[J]. Int J Gastrointest Cancer， 2005， 35(1)：61-68.
19. Temel RE， Tang W， Ma Y， et al. Hepatic Niemann-Pick C1-like 1 regulates biliary cholesterol concentration and is a targetof ezetimibe[J]. J Clin Invest， 2007， 117(7)：1968-1978.
20. Altmann SW， Davis HR Jr， Zhu LJ， et al. Niemann-Pick C1 like 1 protein is critical for intestinal cholesterol absorption[J]. Science， 2004， 303(5661)：1201-1204.
21. Davis HR Jr， Zhu LJ， Hoos LM， et al. Niemann-Pick C1 like 1 (NPC1L1) is the intestinal phytosterol and cholesterol transporter and a key modulator of whole-body cholesterol homeostasis[J]. J Biol Chem， 2004， 279(32)：33586-33592.
22. Davies JP， Scott C， Oishi K， et al. Inactivation of NPC1L1 causes multiple lipid transport defects and protects against diet-induced hypercholesterolemia[J]. J Biol Chem， 2005， 280(13)：12710-12720.
23. Sané AT， Sinnett D， Delvin E， et al. Localization and role of NPC1L1 in cholesterol absorption in human intestine[J]. JLipid Res， 2006， 47(10)：2112-2120.
24. Eberlé D， Hegarty B， Bossard P， et al. SREBP transcription factors：master regulators of lipid homeostasis[J]. Biochimie， 2004， 86(11)：839-848.
25. Brown MS， Goldstein JL. The SREBP pathway：regulation of cholesterol metabolism by proteolysis of a membrane-bound transcription factor[J]. Cell， 1997， 89(3)：331-340.
26. Horton JD， Goldstein JL， Brown MS. SREBPs：activators of the complete program of cholesterol and fatty acid synthesis in the liver[J]. J Clin Invest， 2002， 109(9)：1125-1131.
27. Goldstein JL， Brown MS. Binding and degradation of low density lipoproteins by cultured human fibroblasts. Comparison of cells from a normal subject and from a patient with homozygous familial hypercholesterolemia[J]. J Biol Chem， 1974， 249(16)：5153-5162.
28. Brown MS， Goldstein JL. A receptor-mediated pathway for cholesterol homeostasis[J]. Science， 1986， 232(4746)：34-47.
29. Duan LP， Wang HH， Ohashi A， et al. Role of intestinal sterol transporters Abcg5， Abcg8， and Npc1l1 in cholesterol absorption in mice：gender and age effects[J]. Am J Physiol Gastrointest Liver Physiol， 2006， 290(2)：G269-G276.
30. Plösch T， Bloks VW， Terasawa Y， et al. Sitosterolemia in ABC-transporter G5-deficient mice is aggravated on activation of the liver-X receptor[J]. Gastroenterology， 2004， 126(1)：290-300.
31. Wang HH， Patel SB， Carey MC， et al. Increased cholesterol and sitostanol absorption and reduced biliary cholesterol secretion in ATP-binding cassette transporter Abcg8 (-/-) mice[J]. Gastroenterology， 2005， 128：A678.
32. Yu L， Hammer RE， Li-Hawkins J， et al. Disruption of Abcg5 and Abcg8 in mice reveals their crucial role in biliary cholesterol secretion[J]. Proc Natl Acad Sci USA， 2002， 99(25)：16237-16242.
33. Duan LP， Wang HH， Wang DQ. Cholesterol absorption is mainly regulated by the jejunal and ileal ATP-binding cassette sterol efflux transporters Abcg5 and Abcg8 in mice[J]. J Lipid Res， 2004， 45(7)：1312-1323.
34. Wang DQ， Tazuma S， Cohen DE， et al. Feeding natural hydrophilic bile acids inhibits intestinal cholesterol absorption：studies in the gallstone-susceptible mouse[J]. Am J Physiol Gastrointest Liver Physiol， 2003， 285(3)：G494-G502.
35. Brown AC， Wrenn SP， Suresh N， et al. Gender differences in cholesterol nucleation in native bile：estrogen is a potential contributory factor[J]. J Membr Biol， 2009， 232(1-3)：35-45.
36. George KS， Wu S. Lipid raft：A floating island of death or survival[J]. Toxicol Appl Pharmacol， 2012， 259(3)：311-319.
37. Pani B， Singh BB. Lipid rafts/caveolae as microdomains of calcium signaling[J]. Cell calcium， 2009， 45(6)：625-633.
38. Whiting KP， Restall CJ， Brain PF. Steroid hormone-induced effects on membrane fluidity and their potential roles in non-genomic mechanisms[J]. Life Sci， 2000， 67(7)：743-757.
39. Filardo EJ， Quinn JA， Sabo E. Association of the membrane estrogen receptor， GPR30， with breast tumor metastasis and transactivation of the epidermal growth factor receptor[J]. Steroids， 2008， 73(9-10)：870-873.
40. Filardo EJ， Thomas P. GPR30：a seven-transmembrane-spanning estrogen receptor that triggers EGF release[J]. Trends Endocrinol Metab， 2005， 16(8)：362-367.
41. Tierney S， Qian Z， Burrow C， et al. Estrogen inhibits sphincter of Oddi motility[J]. J Surg Res， 1994， 57(1)：69-73.
42. Kiaii B， Xu QW， Shaffer EA. The basis for progesterone impairment of gallbladder contractility in male Guinea pigs in vitro[J]. J Surg Res， 1998， 79(2)：97-102.
43. Chen Q， Chitinavis V， Xiao Z， et al. Impaired G protein function in gallbladder muscle from progesterone-treated Guinea pigs[J]. Am J Physiol， 1998， 274(2 pt 1)：G283-G289.
44. Cong P， Pricolo V， Biancani P， et al. High levels of caveolar cholesterol inhibit progesterone-induced genomic actions in human and Guinea pig gallbladder muscle[J]. Am J Physiol Gastrointest Liver Physiol， 2009， 296(4)：G948-G954.
45. Tierney S， Nakeeb A， Wong O， et al. Progesterone alters biliary flow dynamics[J]. Ann Surg， 1999， 229(2)：205-209.
46. Xiao ZL， Biancani P， Behar J. Effects of progesterone on motility and prostaglandin levels in the distal Guinea pig colon[J]. Am J Physiol Gastrointest Liver Physiol， 2009， 297(5)：G886-G893.
47. Chen Q， Xiao ZL， Biancani P， et al. Downregulation of galphaq-11 protein expression in Guinea pig antral and colonic circular muscle during pregnancy[J]. Am J Physiol， 1999， 276(4 Pt 1)：G895-G900.
48. Xiao ZL， Chen Q， Biancani P， et al. Mechanisms of gallbladder hypomotility in pregnant Guinea pigs[J]. Gastroenterology， 1999， 116(2)：411-419.
49. Cheng L， Pricolo V， Biancani P， et al. Overexpression of progesterone receptor B increases sensitivity of human colon muscle cells to progesterone[J]. Am J Physiol Gastrointest Liver Physiol， 2008， 295(3)：G493-G502.
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《中國普外基礎與臨床雜志》

女性激素在膽囊膽固醇結石形成中的作用的研究現狀

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《中國普外基礎與臨床雜志》

女性激素在膽囊膽固醇結石形成中的作用的研究現狀

摘要 全文 圖表 視頻 參考文獻 施引文獻 補充材料

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摘要全文圖表視頻參考文獻施引文獻補充材料