胆囊结石患者胆囊动力学变化相关研究
|
摘要
目的：探讨胆囊动力学异常在胆囊结石形成中的作用,为明确保胆取石手术适应证提供依据。方法：50例胆囊结石病人(病例组)和20例健康人(正常对照组),采用B超测定空腹胆囊壁厚度、空腹胆囊容积、餐后30min、60 min、90 min胆囊餐后残余容积,计算胆囊排空容积EV、胆囊残余指数RF和胆囊排空率E。病例组以正常对照组平均RF+2SD值(40.18%)为界限,分为胆囊收缩“正常”组(n=12)和胆囊收缩“减弱”组两个亚组(n=38)。结果：1)正常对照组胆囊壁厚度0.15±0.03cm,胆囊排空率(71.88±6.03)%。根据参数可信区间的计算方法,正常健康人胆囊壁厚度95%的可信区间为0.09-0.21 cm,胆囊排空率95%的可信区间为59.82%-83.94%。2)病例组胆囊壁厚度0.31±0.05cm,胆囊排空率(48.65±15.81)%,与正常对照组比较均有显著差异(P<0.05)。3)胆囊结石患者胆囊收缩“正常”组胆囊壁厚度0.28±0.05 cm,胆囊收缩“减弱”组胆囊壁厚度0.32±0.05 cm,与正常对照组比较,均有显著差异(P<0.05),胆囊收缩“正常”组与胆囊收缩“减弱”组胆囊壁厚度比较也有显著差异(P<0.05)。4)胆囊结石患者胆囊收缩“减弱”组与胆囊收缩“正常”组比较,虽然FV没有明显差异(P>0.05),但胆囊收缩“减弱”组最小残余容积增大(P<0.05),胆囊排空率降低(P<0.05)。胆囊结石患者胆囊收缩“正常”组与正常对照组比较,虽然排空率没有明显差异,但胆囊收缩“正常”组空腹胆囊容积明显增大(P<0.05)。5)病例组胆囊结石患者的胆囊排空率与胆囊壁厚度二者呈显著负相关,Y=106.695-185.270X,r=-0.617,P=0.000；对照组胆囊排空率与胆囊壁厚度二者无相关,Y=77.846-38.986X,r=-0.184,P=0.437。结论：胆囊排空障碍是胆囊结石形成的动力学基础之一,为临床用药防止胆囊结石形成及复发、保胆取石术手术适应证的选择提供了理论依据。我们认为保胆取石术应具备的基本条件是胆囊排空率>50%,胆囊壁厚度≤0.3cm。
目的：探讨胆囊结石患者胆囊收缩素(CCK)-A受体mRNA转录水平和受体分布、定位及蛋白表达水平。方法：50例胆囊结石患者(病例组)和20例无胆囊结石肝移植供体(供体组)胆囊标本,采用RT-PCR方法测定胆囊标本CCK-A受体分子mRNA转录水平,采用酶免疫组织化学法研究胆囊CCK-A受体的分布和定位,测定胆囊标本CCK-A受体分子蛋白表达水平。结果：1)供体组胆囊CCK-A受体分子mRNA转录水平0.8182±0.0481,病例组mRNA转录水平0.6465±0.0910,两组比较有明显差异(P<0.01)。2)胆囊CCK-A受体分子不仅在胆囊平滑肌细胞表达,而且在腺上皮细胞也有明显表达。蛋白表达阳性细胞中,细胞核与细胞浆均有表达。3)与供体组相比,病例组免疫组化染色5个高倍视野中腺上皮细胞、平滑肌细胞蛋白表达阳性细胞数明显减少,两组比较有显著差异(P<0.01)。4)供体组胆囊CCK-A受体分子蛋白表达水平(蛋白表达阳性细胞总数)和mRNA转录水平呈正相关,Y=-458.027+975.883X,r=0.741,P=0.000；病例组胆囊CCK-A受体分子蛋白表达水平(蛋白表达阳性细胞总数)和mRNA转录水平也呈正相关,Y=-43.193+414.018X,r=0.644,P=0.000。结论：1)胆囊收缩素与胆囊CCK-A受体结合,不仅调节胆囊平滑肌收缩,而且还调节胆囊腺上皮细胞的分泌功能。2)胆囊CCK-A受体属于胞核和胞质受体(胞内受体)。3)胆囊结石患者CCK-A受体分子mRNA转录水平和蛋白表达水平较低。4)胆囊结石患者胆囊CCK-A受体分子蛋白表达水平降低与mRNA转录水平下调是一致的。
目的：探讨胆囊结石患者胆囊CCK-A受体分子mRNA转录水平和蛋白表达水平对胆囊收缩功能的影响。方法：同第二部分研究。结果：1)将病例组患者的两个亚组(胆囊收缩“正常”组12例和收缩“减弱”组38例)进行比较,胆囊收缩“减弱”组CCK-A受体mRNA转录水平显著低于胆囊收缩“正常”组(0.6279±0.0900比0.7055±0.0680,P<0.01)；即使是胆囊收缩“正常”的胆石病患者,胆囊CCK-A受体mRNA转录水平也较无胆囊结石的供体组减少(0.7055±0.0680比0.8182±0.0481,P<0.01)。2)供体组20例,胆囊平滑肌细胞蛋白表达阳性7例、强阳性13例,而病例组50例,平滑肌细胞蛋白表达弱阳性24例、阳性22例、强阳性4例,二者比较有显著差异(P<0.01)。病例组和供体组胆囊平滑肌CCK-A受体蛋白表达阳性细胞数比较也有显著差异(P<0.01)。将病例组的两个亚组进行比较,胆囊收缩“减弱”组胆囊平滑肌CCK-A受体分子蛋白表达阳性强度和阳性细胞数显著低于无胆囊结石的供体组(P<0.01);即使是胆囊收缩“正常”的胆囊结石患者,胆囊平滑肌CCK-A受体分子蛋白表达阳性强度和阳性细胞数也较无胆囊结石的供体组低(P<0.05)。胆囊收缩“减弱”组和胆囊收缩“正常”组胆囊平滑肌CCK-A受体分子蛋白表达水平比较,表达阳性强度有显著差异(P<0.05),但蛋白表达阳性细胞数无差异(P>0.05)。3)病例组胆囊CCK-A受体mRNA转录水平与胆囊壁厚度二者呈显著负相关,Y=0.965-1.019X,r=-0.582,P=0.000;病例组胆囊平滑肌CCK-A受体蛋白表达水平(平滑肌蛋白表达阳性细胞总数)与胆囊壁厚度二者呈显著负相关,Y=193.784-246.306X,r=-0.419,P=0.002.4)病例组胆囊排空率与胆囊CCK-A受体mRNA转录水平二者呈显著正相关,Y=-37.558+133.493X,r=0.778,P=0.000；病例组胆囊排空率与胆囊平滑肌CCK-A受体蛋白表达水平(平滑肌蛋白表达阳性细胞总数)二者呈显著正相关Y=13.725+0.300X,r=0.587,P=0.000。结论：胆囊结石患者CCK-A受体分子1nRNA转录水平和蛋白表达水平与胆囊壁厚度、胆囊排空率存在数量上的相关关系,CCK-A受体分子mRNA转录水平和蛋白表达水平的差异可能是影响胆囊收缩功能的关键因素。
目的：探讨胆囊结石患者胆汁胆固醇浓度对胆囊CCK-A受体分子mRNA转录水平和蛋白表达水平的影响。方法：采用酶法测定胆汁胆固醇浓度,其余方法同第二、三部分研究。结果：1)供体组胆汁胆固醇浓度6.68±1.75mmol/L,病例组胆汁胆固醇浓度9.40±2.33mmol/L,二者比较有显著差异(P<0.01)。将病例组患者的两个亚组进行比较,胆囊收缩“减弱”组胆汁胆固醇浓度显著低于胆囊收缩“正常”组,P<0.05,但胆囊收缩“正常”组胆汁胆固醇浓度和无胆囊结石的肝移植供体供体组比较,无显著差异,P>0.05。2)胆囊壁厚度与胆汁胆固醇浓度二者呈显著正相关,Y=0.186+0.014X,r=0.608,P=0.000.3)病例组胆囊排空率与胆汁胆固醇浓度二者呈显著负相关,Y=98.686-5.314X,r=-0.795,P=0.000。4)供体组CCK-A受体mRNA转录水平与胆汁胆固醇浓度二者呈显著负相关,Y=0.961-0.021X,r=-0.776,P=0.000:病例组CCK-A受体mRNA转录水平与胆汁胆固醇浓度二者也呈显著负相关,Y=0.934-0.031X,r=-0.786,P=0.000。5)供体组胆囊CCK-A受体总蛋白表达水平(腺上皮和平滑肌细胞蛋白表达阳性细胞总数)与胆汁胆固醇浓度呈负相关,Y=523.268-27.358X,r=-0.757,P=0.000；病例组胆囊CCK-A受体总蛋白表达水平(腺上皮和平滑肌细胞蛋白表达阳性细胞总数)与胆汁胆固醇浓度也呈负相关,Y=365.440-15.000X,r=-0.599,P=0.000.6)供体组胆囊平滑肌CCK-A受体蛋白表达水平(平滑肌蛋白表达阳性细胞数)与胆汁胆固醇浓度呈负相关,Y=301.824-19.120X,r=-0.667,P=0.001;病例组胆囊平滑肌CCK-A受体蛋白表达水平(平滑肌蛋白表达阳性细胞数)与胆汁胆固醇浓度也呈负相关,Y=190.866-7.887X,r=-0.603,P=0.000.结论：1)胆囊结石患者的胆汁胆固醇浓度高于无胆囊结石的人,尤其是胆囊收缩功能差的胆囊结石患者,胆汁胆固醇浓度明显升高。2)胆囊的慢性炎症与胆汁胆固醇浓度有关。3)无论是胆囊结石患者,还是非胆囊结石的肝移植供体,胆囊CCK-A受体分子mRNA转录水平和蛋白表达水平随着胆汁胆固醇浓度的高低而下调或上调,表明胆汁胆固醇可能是胆囊收缩功能障碍的始动因素,降低胆汁高胆固醇浓度可以促进胆囊动力功能的恢复,为预防结石的形成或复发提供了理论基础。
Objective:To find the role of abnormal gallbladder dynamics in gallstone formation and to provide evidence for choosing indications of gallstone removal with gallbladder preservation surgery. Methods:50 cases of gallstone patients (patient group) and 20 healthy individuals (control group) were chosen. Type-B ultrasonic was adopted to measure gallbladder wall thickness and gallbladder full volume (FV) for patients under starvation condition, and measure gallbladder residual volume (RV) for patients at 30 minutes (min),60 min, and 90 min post-meal. The minimum RV (RVmin) was chosen. Gallbladder emptying volume (EV)=FV-RVmin. Gallbladder residual factor (RF)=(RV/FV)×100%. Gallbladder emptying efficiency (E)=(1-RF). By defining average RF+2SD (40.18%) in control group as a baseline, patient group had been divided into "normal" gallbladder contraction group (n=12) and "weakening" gallbladder contraction group (n=38). Results:1) Gallbladder wall thickness of control group was 0.15±0.03 cm. Gallbladder emptying efficiency in control group was (71.88±6.03)%. According to confidence interval calculation of parameter, gallbladder wall thickness in control group was 0.09～0.21 cm with 95% confidence interval. Gallbladder emptying efficiency in control group was 59.82%～83.94% with 95% confidence interval.2) Gallbladder wall thickness of patient group was 0.31±0.05 cm. Gallbladder emptying efficiency in patient group was (48.65±15.81)%. Gallbladder wall thickness and emptying efficiency were significantly different between patient group and control group (P<0.05).3) Gallbladder wall thickness of "normal" gallbladder contraction group was 0.28±0.05 cm,and wall thickness of "weakening" gallbladder contraction group was 0.31±0.05cm. In comparison of two sub-groups, "normal" and "weakening" groups, with control group, there was significant difference (P<0.05). There was also significant difference between "weakening" gallbladder contraction group and "normal" group (P<0.05).4) Compare to "normal" group, FV had no significant change, but RV increased (P<0.05), gallbladder emptying efficiency (E%) decreased (P<0.05), EV decreased significantly (P<0.05) in "weakening" group. Comparing the "normal" group to control group, although E had no significant change, FV increased dramatically (P<0.05).5)There is significant negative correlation between gallbladder emptying efficiency and gallbladder wall thickness in patient group (Y=106.695-185.270X, r=-0.617, P=0.000),while there was no significant correlation between them within control group (Y=77.846-38.986X, r=-0.184, P=0.437). Conclusion:The gallbladder emptying dysfunction is the fundamental for gallstone formation, and offered theoretical evidence for choosing chemotherapy to prevent gallstone formation and relapse and selecting indications of gallstone removal with gallbladder preservation surgery. Thus, we concluded that the prerequisite for gallstone removal with gallbladder preservation surgery are gallbladder emptying efficiency>50%, and gallbladder wall thickness≤0.3 cm.
Objective:To study the CCK-A receptor's location and its protein production and mRNA expression levels in gallstone patients. Methods:50 cholesterol calculus patients (patient group) and 20 liver transplant provider (provider group) were chosen. CCK-A receptor mRNA transcription level between patient and provider groups had been tested by reverse transcription (RT)-PCR, and CCK-A receptor's location and its protein production level between patient and provider groups had been tested by immunohistology (IH). Results:1) The level of CCK-A receptor mRNA transcription is 0.6465±0.0910 in patient group, and the mRNA expression is 0.8182±0.0481 in provider group; There is significant difference between the two groups (P<0.01).2) Gallbladder CCK-A receptor was not only expressed in gallbladder smooth muscle cells, but also expressed in gallbladder epithelial cells. CCK-A receptor was present in both nucleus and cytoplasm within CCK-A receptor positive expressed cell.3) Compare to provider group, number of CCK-A receptor positive expressed gallbladder epithelial and gallbladder smooth muscle cells had decreased dramatically under 5 high power field (hpf) within patient group.4) There is positive correlation between CCK-A receptor protein production level (total CCK-A positive expressed cell number) and mRNA transcription level in provider group (Y=-458.027+ 975.883X, r=0.741, P=0.000), and there is the same type of correlation in patient group as well(Y=-43.193+414.018X, r=0.644, P=0.000). Conclusion:1) The binding of CCK-A and CCK-A receptor can not only adjust gallbladder smooth muscle contraction, but also secretory function of gallbladder epithelial cells.2) CCK-A receptor belongs to both nucleus and cytoplasm receptor.3) CCK-A receptor protein production level and mRNA transcription level are both low in gallstone patient.4) Decreased level of CCK-A receptor protein production level is consistent with decreased mRNA transcription level within gallstone patient.
Objective:To study the effect of levels of CCK-A receptor mRNA transcription and protein production on gallbladder contraction in gallstone patients. Methods: The methods are the same as partⅠand partⅡ. Results:1) CCK-A receptor mRNA transcription level in "weakening" gallbladder contraction group was significantly lower than "normal" gallbladder contraction group (0.6279±0.0900 vs 0.7055±0.0680, P<0.01); CCK-A receptor mRNA transcription level was still lower than that of provider group (0.7055±0.080 vs 0.8182±0.0481, P<0.01) even in "normal" group.2) Within 20 cases in provider group, there were 7 regular CCK-A receptor positive expressed smooth muscle cells, and 13 strong CCK-A receptor positive expressed smooth muscle cells, within 50 cases in patient group, there were 24 weak CCK-A receptor positive expressed smooth muscle cells,22 regular CCK-A receptor positive expressed smooth muscle cells, and 4 strong CCK-A receptor positive expressed smooth muscle cells, while there are significant difference between patient and provider groups (P<0.01). CCK-A positive expressed cell number between patient and provider groups are also significantly different (P<0.01). CCK-A receptor protein production level and positive expressed cell number of gallbladder smooth muscle in "weakening" gallbladder contraction group are significantly lower than that of provider group(P<0.01); Even within "normal" gallbladder contraction group, CCK-A receptor protein production level and positive expressed cell number are significantly lower than that of provider group (P<0.05). There are significant difference of CCK-A receptor protein production level (P<0.05),but there are no significant difference of CCK-A receptor protein positive expressed cell number between "normal" and "weakening" groups (P>0.05).3)There is negative correlation between CCK-A receptor mRNA transcription level and gallbladder wall thickness in patient group (Y=0.965-1.019X, r=-0.582, P=0.000).4) There is negative correlation between CCK-A receptor protein production level and gallbladder wall thickness in patient group (Y=193.784-246.306X, r=-0.419, P=0.002).5) There is positive correlation between gallbladder emptying efficiency and CCK-A receptor mRNA transcription level in patient group (Y=-37.558+133.493X, r=0.778, P= 0.000); There is positive correlation between gallbladder emptying efficiency and CCK-A receptor protein production level in gallbladder smooth muscle (CCK-A positive expressed cell number in gallbladder smooth muscle) in patient group (Y=13.725+0.300X, r=0.587, P=0.000). Conclusion:1) There is quantitative relationship between levels of CCK-A receptor protein production and mRNA transcription and gallbladder thickness and emptying efficiency within gallstone patients, the difference between CCK-A receptor protein production level and mRNA transcription level may determine the extent of gallbladder contraction dysfunction.
Objective:to study the effect of biliary cholesterol concentration on CCK-A receptor mRNA transcription and protein production in gallstone patients. Methods: The biliary cholesterol concentration had been tested by biochemistry. The other methods are the same as partⅠand partⅡ. Results:1)Biliary cholesterol concentration is 6.68±1.75 mmol/L, in provider group, and is 9.40±2.33 mmol/L, in patient group; There is significant difference between the two groups (P<0.01). In comparison of two sub-groups, "normal" and "weakening" groups, with provider group, there was significant difference between "weakening" gallbladder contraction group and provider group (P<0.05), but no difference between "normal" gallbladder contraction group and provider group (P>0.05); 2)There is significant positive correlation between gallbladder wall thickness and biliary cholesterol concentration (Y=0.186+0.014X, r=0.608, P=0.000) in patient group; 3) There is significant negative correlation between gallbladder evacuation efficiency and biliary cholesterol concentration in patient group (Y=98.686-5.314X, r=-0.795, P=0.000); 4) there is significant negative correlation between CCK-A receptor mRNA transcription level and biliary cholesterol concentration in both provider group (Y=0.961-0.021X, r=-0.776, P=0.000), and patient group (Y=0.934-0.031X, r=-0.786, P=0.000); 5)There is significant negative correlation between CCK-A receptor protein production(total CCK-A positive expressed cell number)and biliary cholesterol concentration in provider group (Y=523.268-27.358X, r=-0.757,P=0.000); There is significant negative correlation between CCK-A receptor protein production(total CCK-A positive expressed cell number)and biliary cholesterol concentration in patient group (Y=365.440-15.000X, r=-0.599, P=0.000).6) There is significant negative correlation between CCK-A receptor protein production level in gallbladder smooth muscle (CCK-A positive expressed cell number in gallbladder smooth muscle) and biliary cholesterol concentration in provider group (Y=301.824-19.120X, r=-0.667, P=0.001); There is significant negative correlation between CCK-A receptor protein production level in gallbladder smooth muscle (CCK-A positive expressed cell number in gallbladder smooth muscle) and biliary cholesterol concentration in patient group (Y=190.866-7.887X, r=-0.603, P=0.000). Conclusion:1) Biliary cholesterol concentration from gallstone patients is significantly higher than that of healthy individuals, especially the patients with weak gallbladder contraction function, whose biliary cholesterol concentrations increase dramatically.2) Gallbladder chronic inflammation is related to biliary cholesterol concentration.3) Within both gallstone patients and liver transplant provider, CCK-A receptor mRNA expression and protein production levels increase or decrease as biliary cholesterol concentration increases or decreases. Thus, biliary cholesterol is the initiative factor for gallbladder contraction dysfunction, decreased biliary cholesterol concentration can improve the recovery of gallbladder dynamic function, and provides theoretical basis for preventing gallstone formation and relapse.
目的：探讨胆囊结石患者胆囊收缩素(CCK)-A受体mRNA转录水平和受体分布、定位及蛋白表达水平。方法：50例胆囊结石患者(病例组)和20例无胆囊结石肝移植供体(供体组)胆囊标本,采用RT-PCR方法测定胆囊标本CCK-A受体分子mRNA转录水平,采用酶免疫组织化学法研究胆囊CCK-A受体的分布和定位,测定胆囊标本CCK-A受体分子蛋白表达水平。结果：1)供体组胆囊CCK-A受体分子mRNA转录水平0.8182±0.0481,病例组mRNA转录水平0.6465±0.0910,两组比较有明显差异(P<0.01)。2)胆囊CCK-A受体分子不仅在胆囊平滑肌细胞表达,而且在腺上皮细胞也有明显表达。蛋白表达阳性细胞中,细胞核与细胞浆均有表达。3)与供体组相比,病例组免疫组化染色5个高倍视野中腺上皮细胞、平滑肌细胞蛋白表达阳性细胞数明显减少,两组比较有显著差异(P<0.01)。4)供体组胆囊CCK-A受体分子蛋白表达水平(蛋白表达阳性细胞总数)和mRNA转录水平呈正相关,Y=-458.027+975.883X,r=0.741,P=0.000；病例组胆囊CCK-A受体分子蛋白表达水平(蛋白表达阳性细胞总数)和mRNA转录水平也呈正相关,Y=-43.193+414.018X,r=0.644,P=0.000。结论：1)胆囊收缩素与胆囊CCK-A受体结合,不仅调节胆囊平滑肌收缩,而且还调节胆囊腺上皮细胞的分泌功能。2)胆囊CCK-A受体属于胞核和胞质受体(胞内受体)。3)胆囊结石患者CCK-A受体分子mRNA转录水平和蛋白表达水平较低。4)胆囊结石患者胆囊CCK-A受体分子蛋白表达水平降低与mRNA转录水平下调是一致的。
目的：探讨胆囊结石患者胆囊CCK-A受体分子mRNA转录水平和蛋白表达水平对胆囊收缩功能的影响。方法：同第二部分研究。结果：1)将病例组患者的两个亚组(胆囊收缩“正常”组12例和收缩“减弱”组38例)进行比较,胆囊收缩“减弱”组CCK-A受体mRNA转录水平显著低于胆囊收缩“正常”组(0.6279±0.0900比0.7055±0.0680,P<0.01)；即使是胆囊收缩“正常”的胆石病患者,胆囊CCK-A受体mRNA转录水平也较无胆囊结石的供体组减少(0.7055±0.0680比0.8182±0.0481,P<0.01)。2)供体组20例,胆囊平滑肌细胞蛋白表达阳性7例、强阳性13例,而病例组50例,平滑肌细胞蛋白表达弱阳性24例、阳性22例、强阳性4例,二者比较有显著差异(P<0.01)。病例组和供体组胆囊平滑肌CCK-A受体蛋白表达阳性细胞数比较也有显著差异(P<0.01)。将病例组的两个亚组进行比较,胆囊收缩“减弱”组胆囊平滑肌CCK-A受体分子蛋白表达阳性强度和阳性细胞数显著低于无胆囊结石的供体组(P<0.01);即使是胆囊收缩“正常”的胆囊结石患者,胆囊平滑肌CCK-A受体分子蛋白表达阳性强度和阳性细胞数也较无胆囊结石的供体组低(P<0.05)。胆囊收缩“减弱”组和胆囊收缩“正常”组胆囊平滑肌CCK-A受体分子蛋白表达水平比较,表达阳性强度有显著差异(P<0.05),但蛋白表达阳性细胞数无差异(P>0.05)。3)病例组胆囊CCK-A受体mRNA转录水平与胆囊壁厚度二者呈显著负相关,Y=0.965-1.019X,r=-0.582,P=0.000;病例组胆囊平滑肌CCK-A受体蛋白表达水平(平滑肌蛋白表达阳性细胞总数)与胆囊壁厚度二者呈显著负相关,Y=193.784-246.306X,r=-0.419,P=0.002.4)病例组胆囊排空率与胆囊CCK-A受体mRNA转录水平二者呈显著正相关,Y=-37.558+133.493X,r=0.778,P=0.000；病例组胆囊排空率与胆囊平滑肌CCK-A受体蛋白表达水平(平滑肌蛋白表达阳性细胞总数)二者呈显著正相关Y=13.725+0.300X,r=0.587,P=0.000。结论：胆囊结石患者CCK-A受体分子1nRNA转录水平和蛋白表达水平与胆囊壁厚度、胆囊排空率存在数量上的相关关系,CCK-A受体分子mRNA转录水平和蛋白表达水平的差异可能是影响胆囊收缩功能的关键因素。
目的：探讨胆囊结石患者胆汁胆固醇浓度对胆囊CCK-A受体分子mRNA转录水平和蛋白表达水平的影响。方法：采用酶法测定胆汁胆固醇浓度,其余方法同第二、三部分研究。结果：1)供体组胆汁胆固醇浓度6.68±1.75mmol/L,病例组胆汁胆固醇浓度9.40±2.33mmol/L,二者比较有显著差异(P<0.01)。将病例组患者的两个亚组进行比较,胆囊收缩“减弱”组胆汁胆固醇浓度显著低于胆囊收缩“正常”组,P<0.05,但胆囊收缩“正常”组胆汁胆固醇浓度和无胆囊结石的肝移植供体供体组比较,无显著差异,P>0.05。2)胆囊壁厚度与胆汁胆固醇浓度二者呈显著正相关,Y=0.186+0.014X,r=0.608,P=0.000.3)病例组胆囊排空率与胆汁胆固醇浓度二者呈显著负相关,Y=98.686-5.314X,r=-0.795,P=0.000。4)供体组CCK-A受体mRNA转录水平与胆汁胆固醇浓度二者呈显著负相关,Y=0.961-0.021X,r=-0.776,P=0.000:病例组CCK-A受体mRNA转录水平与胆汁胆固醇浓度二者也呈显著负相关,Y=0.934-0.031X,r=-0.786,P=0.000。5)供体组胆囊CCK-A受体总蛋白表达水平(腺上皮和平滑肌细胞蛋白表达阳性细胞总数)与胆汁胆固醇浓度呈负相关,Y=523.268-27.358X,r=-0.757,P=0.000；病例组胆囊CCK-A受体总蛋白表达水平(腺上皮和平滑肌细胞蛋白表达阳性细胞总数)与胆汁胆固醇浓度也呈负相关,Y=365.440-15.000X,r=-0.599,P=0.000.6)供体组胆囊平滑肌CCK-A受体蛋白表达水平(平滑肌蛋白表达阳性细胞数)与胆汁胆固醇浓度呈负相关,Y=301.824-19.120X,r=-0.667,P=0.001;病例组胆囊平滑肌CCK-A受体蛋白表达水平(平滑肌蛋白表达阳性细胞数)与胆汁胆固醇浓度也呈负相关,Y=190.866-7.887X,r=-0.603,P=0.000.结论：1)胆囊结石患者的胆汁胆固醇浓度高于无胆囊结石的人,尤其是胆囊收缩功能差的胆囊结石患者,胆汁胆固醇浓度明显升高。2)胆囊的慢性炎症与胆汁胆固醇浓度有关。3)无论是胆囊结石患者,还是非胆囊结石的肝移植供体,胆囊CCK-A受体分子mRNA转录水平和蛋白表达水平随着胆汁胆固醇浓度的高低而下调或上调,表明胆汁胆固醇可能是胆囊收缩功能障碍的始动因素,降低胆汁高胆固醇浓度可以促进胆囊动力功能的恢复,为预防结石的形成或复发提供了理论基础。
Objective:To find the role of abnormal gallbladder dynamics in gallstone formation and to provide evidence for choosing indications of gallstone removal with gallbladder preservation surgery. Methods:50 cases of gallstone patients (patient group) and 20 healthy individuals (control group) were chosen. Type-B ultrasonic was adopted to measure gallbladder wall thickness and gallbladder full volume (FV) for patients under starvation condition, and measure gallbladder residual volume (RV) for patients at 30 minutes (min),60 min, and 90 min post-meal. The minimum RV (RVmin) was chosen. Gallbladder emptying volume (EV)=FV-RVmin. Gallbladder residual factor (RF)=(RV/FV)×100%. Gallbladder emptying efficiency (E)=(1-RF). By defining average RF+2SD (40.18%) in control group as a baseline, patient group had been divided into "normal" gallbladder contraction group (n=12) and "weakening" gallbladder contraction group (n=38). Results:1) Gallbladder wall thickness of control group was 0.15±0.03 cm. Gallbladder emptying efficiency in control group was (71.88±6.03)%. According to confidence interval calculation of parameter, gallbladder wall thickness in control group was 0.09～0.21 cm with 95% confidence interval. Gallbladder emptying efficiency in control group was 59.82%～83.94% with 95% confidence interval.2) Gallbladder wall thickness of patient group was 0.31±0.05 cm. Gallbladder emptying efficiency in patient group was (48.65±15.81)%. Gallbladder wall thickness and emptying efficiency were significantly different between patient group and control group (P<0.05).3) Gallbladder wall thickness of "normal" gallbladder contraction group was 0.28±0.05 cm,and wall thickness of "weakening" gallbladder contraction group was 0.31±0.05cm. In comparison of two sub-groups, "normal" and "weakening" groups, with control group, there was significant difference (P<0.05). There was also significant difference between "weakening" gallbladder contraction group and "normal" group (P<0.05).4) Compare to "normal" group, FV had no significant change, but RV increased (P<0.05), gallbladder emptying efficiency (E%) decreased (P<0.05), EV decreased significantly (P<0.05) in "weakening" group. Comparing the "normal" group to control group, although E had no significant change, FV increased dramatically (P<0.05).5)There is significant negative correlation between gallbladder emptying efficiency and gallbladder wall thickness in patient group (Y=106.695-185.270X, r=-0.617, P=0.000),while there was no significant correlation between them within control group (Y=77.846-38.986X, r=-0.184, P=0.437). Conclusion:The gallbladder emptying dysfunction is the fundamental for gallstone formation, and offered theoretical evidence for choosing chemotherapy to prevent gallstone formation and relapse and selecting indications of gallstone removal with gallbladder preservation surgery. Thus, we concluded that the prerequisite for gallstone removal with gallbladder preservation surgery are gallbladder emptying efficiency>50%, and gallbladder wall thickness≤0.3 cm.
Objective:To study the CCK-A receptor's location and its protein production and mRNA expression levels in gallstone patients. Methods:50 cholesterol calculus patients (patient group) and 20 liver transplant provider (provider group) were chosen. CCK-A receptor mRNA transcription level between patient and provider groups had been tested by reverse transcription (RT)-PCR, and CCK-A receptor's location and its protein production level between patient and provider groups had been tested by immunohistology (IH). Results:1) The level of CCK-A receptor mRNA transcription is 0.6465±0.0910 in patient group, and the mRNA expression is 0.8182±0.0481 in provider group; There is significant difference between the two groups (P<0.01).2) Gallbladder CCK-A receptor was not only expressed in gallbladder smooth muscle cells, but also expressed in gallbladder epithelial cells. CCK-A receptor was present in both nucleus and cytoplasm within CCK-A receptor positive expressed cell.3) Compare to provider group, number of CCK-A receptor positive expressed gallbladder epithelial and gallbladder smooth muscle cells had decreased dramatically under 5 high power field (hpf) within patient group.4) There is positive correlation between CCK-A receptor protein production level (total CCK-A positive expressed cell number) and mRNA transcription level in provider group (Y=-458.027+ 975.883X, r=0.741, P=0.000), and there is the same type of correlation in patient group as well(Y=-43.193+414.018X, r=0.644, P=0.000). Conclusion:1) The binding of CCK-A and CCK-A receptor can not only adjust gallbladder smooth muscle contraction, but also secretory function of gallbladder epithelial cells.2) CCK-A receptor belongs to both nucleus and cytoplasm receptor.3) CCK-A receptor protein production level and mRNA transcription level are both low in gallstone patient.4) Decreased level of CCK-A receptor protein production level is consistent with decreased mRNA transcription level within gallstone patient.
Objective:To study the effect of levels of CCK-A receptor mRNA transcription and protein production on gallbladder contraction in gallstone patients. Methods: The methods are the same as partⅠand partⅡ. Results:1) CCK-A receptor mRNA transcription level in "weakening" gallbladder contraction group was significantly lower than "normal" gallbladder contraction group (0.6279±0.0900 vs 0.7055±0.0680, P<0.01); CCK-A receptor mRNA transcription level was still lower than that of provider group (0.7055±0.080 vs 0.8182±0.0481, P<0.01) even in "normal" group.2) Within 20 cases in provider group, there were 7 regular CCK-A receptor positive expressed smooth muscle cells, and 13 strong CCK-A receptor positive expressed smooth muscle cells, within 50 cases in patient group, there were 24 weak CCK-A receptor positive expressed smooth muscle cells,22 regular CCK-A receptor positive expressed smooth muscle cells, and 4 strong CCK-A receptor positive expressed smooth muscle cells, while there are significant difference between patient and provider groups (P<0.01). CCK-A positive expressed cell number between patient and provider groups are also significantly different (P<0.01). CCK-A receptor protein production level and positive expressed cell number of gallbladder smooth muscle in "weakening" gallbladder contraction group are significantly lower than that of provider group(P<0.01); Even within "normal" gallbladder contraction group, CCK-A receptor protein production level and positive expressed cell number are significantly lower than that of provider group (P<0.05). There are significant difference of CCK-A receptor protein production level (P<0.05),but there are no significant difference of CCK-A receptor protein positive expressed cell number between "normal" and "weakening" groups (P>0.05).3)There is negative correlation between CCK-A receptor mRNA transcription level and gallbladder wall thickness in patient group (Y=0.965-1.019X, r=-0.582, P=0.000).4) There is negative correlation between CCK-A receptor protein production level and gallbladder wall thickness in patient group (Y=193.784-246.306X, r=-0.419, P=0.002).5) There is positive correlation between gallbladder emptying efficiency and CCK-A receptor mRNA transcription level in patient group (Y=-37.558+133.493X, r=0.778, P= 0.000); There is positive correlation between gallbladder emptying efficiency and CCK-A receptor protein production level in gallbladder smooth muscle (CCK-A positive expressed cell number in gallbladder smooth muscle) in patient group (Y=13.725+0.300X, r=0.587, P=0.000). Conclusion:1) There is quantitative relationship between levels of CCK-A receptor protein production and mRNA transcription and gallbladder thickness and emptying efficiency within gallstone patients, the difference between CCK-A receptor protein production level and mRNA transcription level may determine the extent of gallbladder contraction dysfunction.
Objective:to study the effect of biliary cholesterol concentration on CCK-A receptor mRNA transcription and protein production in gallstone patients. Methods: The biliary cholesterol concentration had been tested by biochemistry. The other methods are the same as partⅠand partⅡ. Results:1)Biliary cholesterol concentration is 6.68±1.75 mmol/L, in provider group, and is 9.40±2.33 mmol/L, in patient group; There is significant difference between the two groups (P<0.01). In comparison of two sub-groups, "normal" and "weakening" groups, with provider group, there was significant difference between "weakening" gallbladder contraction group and provider group (P<0.05), but no difference between "normal" gallbladder contraction group and provider group (P>0.05); 2)There is significant positive correlation between gallbladder wall thickness and biliary cholesterol concentration (Y=0.186+0.014X, r=0.608, P=0.000) in patient group; 3) There is significant negative correlation between gallbladder evacuation efficiency and biliary cholesterol concentration in patient group (Y=98.686-5.314X, r=-0.795, P=0.000); 4) there is significant negative correlation between CCK-A receptor mRNA transcription level and biliary cholesterol concentration in both provider group (Y=0.961-0.021X, r=-0.776, P=0.000), and patient group (Y=0.934-0.031X, r=-0.786, P=0.000); 5)There is significant negative correlation between CCK-A receptor protein production(total CCK-A positive expressed cell number)and biliary cholesterol concentration in provider group (Y=523.268-27.358X, r=-0.757,P=0.000); There is significant negative correlation between CCK-A receptor protein production(total CCK-A positive expressed cell number)and biliary cholesterol concentration in patient group (Y=365.440-15.000X, r=-0.599, P=0.000).6) There is significant negative correlation between CCK-A receptor protein production level in gallbladder smooth muscle (CCK-A positive expressed cell number in gallbladder smooth muscle) and biliary cholesterol concentration in provider group (Y=301.824-19.120X, r=-0.667, P=0.001); There is significant negative correlation between CCK-A receptor protein production level in gallbladder smooth muscle (CCK-A positive expressed cell number in gallbladder smooth muscle) and biliary cholesterol concentration in patient group (Y=190.866-7.887X, r=-0.603, P=0.000). Conclusion:1) Biliary cholesterol concentration from gallstone patients is significantly higher than that of healthy individuals, especially the patients with weak gallbladder contraction function, whose biliary cholesterol concentrations increase dramatically.2) Gallbladder chronic inflammation is related to biliary cholesterol concentration.3) Within both gallstone patients and liver transplant provider, CCK-A receptor mRNA expression and protein production levels increase or decrease as biliary cholesterol concentration increases or decreases. Thus, biliary cholesterol is the initiative factor for gallbladder contraction dysfunction, decreased biliary cholesterol concentration can improve the recovery of gallbladder dynamic function, and provides theoretical basis for preventing gallstone formation and relapse.
引文
1. Kratzer W,Mason RA,Kachele V.Prevalence of gallstones in sonographic surveys worldwide[J].J Clin Ultrasound,1999,27(1):1-7.
2.韩天权,张圣道.胆石病流行病学研究的现状和发展[J].胃肠病学,2003,8(3)：166-168.
3.中华医学会外科学分会胆道外科学组.我国胆石病十年来的变迁[J].中华外科杂志,1995,33(11)：652-658.
4.陈训如.肝胆外科常见疾病导医指南[M].北京：军事医学科学出版社,2000：185
5.陈希纲,刘家奇,彭民浩,等.胆石病临床流行病学调查[J].中华普通外科杂志,2002,17(2)：99-101
6.石景生,任予.我国胆道外科实验外科研究进展[J].中华实验外科杂志,2004,21(12)：1418-1419
7.粱酉,黄太秀,裴晓红,等.荤素膳食与胆石症发病关系的流行病学调查[J].临床肝胆病杂志,1997,13(3)：152-153.
8. Sandier R S, Everhart J E, Donowitz M,et al. The burden of selected digestive diseases in the United States [J]. Gastroenterology,2002,122 (5):150-153.
9.刘衍民,文辉清,目前保留胆囊手术的几个问题[J].中华外科杂志,2008；46(10)：721-723.
10.张阳德,乔铁,冯禹阳,等.内镜微创外科是治愈疾病及保留器官与器官功能的最佳途径-论内镜下保留胆囊取石或摘除息肉[J].中国内镜杂志,2008,14(5)：449-453.
11.王旭,王翔翔,唐彤,等.内镜保胆取石术临床研究现状[J].中国普外基础与临床杂志,2009；16(9)：773-776.
12.张宝善.关于胆囊结石治疗的争论与Langenbuch理论商榷[J].中国医刊,2007,42(5)：322-325.
13.徐立友,宋钊,付廷海,等.623例内镜取石保胆术[J].中华消化外科杂志,2007,6(6)：459-461.
14.刘京山,李晋忠,赵期康,等.纤维胆道镜下胆囊切开取石保胆治疗胆囊结石612例随访结果分析[J].中华外科杂志,2009,47(2)：279-282.
15.邹一平,萧荫祺.保胆取石术有关问题的探讨[J].中华肝胆外科杂 志,2009,15(1)：1-3.
16. vanBerge-Henegouwen GP, Venneman NG, van Erpecum KJ, et al.Drugs affecting biliary lipid secretion and gallbladder motility:their potential role in gallstone treatment and prevention[J]. Curr Drug Targets Immune Endocr Metabol Disord. 2005;5(2):185-91.
17.宁殿宾,曹文庆,赵玉哲,等,胆囊结石与胆囊收缩素及其受体的关系研究[J].现代中西医结合杂志,2007,16(9)：1157-1158.
18. Zhu J,Han TQ,Chen S,et al. Gallbladder motor function,plasma cholecystokinin and cholecystokinin receptor of gallbladder in cholesterol stone patients[J]. World J Gastroenterol,2005,11(11):1685-1689.
19. Miyasaka K, TaKata Y, Funakoshi A. Association of cholecystokinin A recptor gene polymorphism with cholelithiasis and the molecular mechanisms of this polymorphism[J].J Gastroenterol.2002,37 Suppl 14:102-6.
20. Sato N, Miyasaka K, Suzuki S,et al. Lack of cholecystokinin-A receptor enhanced gallstone formation:a study in CCK-A receptor gene knockout mice[J]. Dig Dis Sci,2003,48(10):1944-1947.
21. Miyasaka K, Kanai S, Ohta M, etal.Age-associated gallstone formation in male and female CCK-1(A) receptor-deficient mice[J]. J Gastroenterol.2007,42(6): 493-496.
22. Kano M, Shoda J, Satoh S,et al. Increased expression of gallbladder cholecystokinin:a receptor in prairie dogs fed a high-cholesterol diet and its dissociation with decreased contractility in response to cholecystokinin[J]. J Lab Clin Med,2002,139(5):285-294.
23. Pozo M J, Camello P J, Mawe G M. Chemical mediators of gallbladder dysmotility[J].Cur Med Chem,2004,11(13):1801-1812.
24.傅华群,吴伟顶,邹书兵,等.胆汁胆固醇对胆囊收缩素受体表达的影响[J].中华外科杂志,2002,40(10)：786-788.
25. Pomeranz IS,Shaffer EA.Abnormal gallbladder emptying in a subgroup of patients with gallstones.Gastroentorology[J];1985,88:787
26 Portincasa P, Moschetta A, Colecchia A,et al.Measurements of gallbladder motor function by ultrasonography:towards standardization[J]. Dig Liver Dis.2003,35 Suppl 3:S56-61.
27.陈胜,韩天权,蒋渝,等.胆囊结石患者胆囊动力学紊乱机制的研究[J].中华外科杂志,1998,36：14.
28. Meltzer D,Egleston B. How patients with diabetes perceive their risk for major complications[J]. Eff Clin Pract,2000,3(1):7-25
29. Okada N, Kuboto A, Imamura T,et al. Evalution of cholecys-tokinin, gastrin, CCK-A receptor and sCCK-8 gastrin receptor gene expression in gastric cancer[J]. Cancer Lett.1996,106(2):257-260.
30. Duellberg SH, Werneck-Silva AL, Sipahy AM,et al. Cholesterol gallstone formation:supersaturation, nucleation and gallbladder motility[J].Rev Hosp Clin Fac Med Sao Paulo.1996,51(5):198-202.
31. Wang HH,Portincasa P,Wang DQ.Molecular pathophysiology and physical chemistry of cholesterol gallstones[J].Front Bios-ci,2008,13(4):401-423.
32.赵纪春,舒哗,程南生,等.胆囊结石中胆固醇代谢变化的实验研究[J].中国普通外科杂志,2000,9：124-126
33.韩天权,蒋兆彦,张圣道.胆结石成因研究进展[J].中国实用外科杂志,2001,21：123-125.
34. Admirand WH. Small DM.The physiochemical basis of cholesterol gallstone formation inman[J]. JClin Invest,1968,47(5):1043-1052.
35. Prigun NP, Korolevich AN. Changes in hu-man biliary vesicle sizes in pathological states [J].Biofizika,2002,47:1095
36. Portincasa P,Venneman NG,Moschetta A, et al. Quantitation of cholesterol crystallization from supersaturated model bile [J]. J Lipid Res,2002,43:604
37. Venneman NG,Huisman SJ,Moschetta A, et al. Effects of hydrophobic and hydrophilic bile salt mixtures on cholesterol crystallization in model biles[J]. Biochim Biophys Acta,2002,1583:221
38. Moschetta A, Vanberge-henegouwen GP,Portincasa P, et al. Cholesterol crystalliza-tion in model biles:effects of bile salt and phospholipid species composition [J]. J Lipid Res,2001,42:1273
39. Sakomoto M,Tazuma S,Chayama K. Less hydrophobic phosphatidylcholine species simplify bil-iary vesicle morphology, but induce bile metastability with a broad spectrum of crystal forms [J]. Biochem J,2002,362:105
40. Gantz DL,Wang DQ,Garey MC, et al. Cryo-electron microscopy of a nucleating model bile in vitreous ice:formation of primordial vesicles [J]. Biophys J, 1999,76:1436
41.吴杰,周建莉,瞿新刚,等.胆汁中各主要有机成分在胆囊结石形成过程中的作用[J].昆明医学院学报,2005,26(4)：4-7.
42. Jiang ZY,Parini P,Eggertsen G,et al.Increased expression of LXR alpha, ABCG5, ABCG8,and SR-BI in the liver from nor-molipidemic,nonobese Chinese gallstone patients[J].J Lipid Res,2008,49(2):464-472.
43.王勇,韩天权,费健,等.胆囊黏膜ABCG5和ABCG8基因在胆固醇结石病中的作用[J].中华实验外科杂志,2007,24(1)：51-52.
44. Behar J. Clinical aspects of gallbladder motor function and dysfunction[J]. Curr Gastroenterol Rep.1999,1(2):91-94.
45. 张继红,杨可桢,韩本立.胆囊结石形成的动力学机制[J].中华普通外科杂志,2001,16(7)：424-426.
46. Jiang ZY,Jiang CY,Wang L,et al.Increased NPC1L1 and ACAT2 expression in the jejunal mucosa from Chinese gallstone patients [J].Biochem Biophys Res Commun,2009,379(1):49-54.
47. Maurer KJ,Rao VP,Ge Z,et al.T-cell function is critical for murine cholesterol gallstone formation[J].Gastroenterology,2007,133(4):1304-1315.
48. Maurer KJ,Carey MC,Fox JGRoles of infection,inflammations, and the immune system in cholesterol gallstone formation[J].Gastroenterology,2009,136(2): 425-440.
49. Maurer KJ,Ihrig MM,Rogers AB,et al.Identification of chole-lithogenic enterohepatic helicobacter species and their role in murine cholesterol gallstone formation[J].Gastroenterology,2005,128(4):1023-1033.
50. 田志杰,韩天权,姜志宏,等.胆囊结石病胆道系统螺杆菌DNA的研究[J].中国实用外科杂志,2004,24(2)：84-87.
51. 郑启昌,魏斌,胡佑化.胆道高压对Oddi括约肌动力学的影响[J].中国病理生理杂志1998,14(5)：469.
52.施维锦.胆道外科学[M].上海：科学技术出版社,1993.27.
53. Rajan M, Wali JP, Sharma MP,et al. Ultrasonographic assessment of gall bladder kinetics in the elderly[J].Indian J Gastroenterol.2000;19(4):158-60.
54. Stads S, Venneman NG, Scheffer RC, et al.Evaluation of gallbladder motility: comparison of two-dimensional and three-dimensional ultrasonography[J]. Ann Hepatol.2007,6(3):164-169.
55. Pallotta N.Ultrasonography in the assessment of gallbladder motor activity[J]. Dig Liver Dis.2003,35 Suppl 3:S67-69.
56. Buchpiguel CA, Sapienza MT, Vezzozzo DP, et al. Gallbladder emptying in normal volunteers. Comparative study between cholescintigraphy and ultrasonography[J].Clin Nucl Med,1996,21:208-212.
57. Down RH, Arnold J, Goldin A, et al.Comparison of accuracy of 99mTc-pyridoxylidene glutamate scanning with oral cholecystography and ultrasonography in diagnosis of acute cholecystitis[J].Lancet,1979,314: 1094-1097.
58. Vyas PK, Vesy TL, Konez O, et al. Estimation of gallbladder ejection fraction utilizing cholecystokinin-stimulated magnetic resonance cholangiography and comparison with hepatobiliary scintigraphy[J]. J Magn Reson Imaging,2002, 15:75-81.
59. Ding X, Gong JP, Lu CY,et al. Relation of abnormal gallbladder arterioles to gallbladder emptying in patients with gallstone and diabetes mellitus[J]. Hepatobiliary Pancreat Dis Int.2004,3(2):275-8.
60.叶生爱,汤文浩.胆囊在胆固醇结石形成中的作用研究进展[J].国外医学外科学分册,2001,28(4)：222-224.
61. Portincasa P, Di Ciaula A, Vendemiale G, et al.Gallbladder motility and cholesterol crystallization in bile from patients with pigment and cholesterol gallstones[J]. Eur J Clin Invest.2000,30(4):317-324.
62. Montet JC, Caroli-Bosc FX, Ferrari P,et al.Gallbladder motility and gut hormone plasma levels in subjects with and without gallstones[J]. Gastroenterol Clin Biol.2005,29(5):569-72.
63. Pauletzk J, Paumgartner G. Defects in gallbladder motfunction-role in gallstone formation and recurrence [J].Aliment Pharmacol Ther,2000,14(suppl 2):32-34.
64 Cerci SS, Ozbek FM, Cerci C,et al.Gallbladder function and dynamics of bile flow in asymptomatic gallstone disease[J]. World J Gastroenterol.2009, 15(22):2763-2767.
65. 帅建,张圣道,韩天权,等.胆囊结石病胆囊排空与缩胆囊素受体基因表达关系的研究[J].中华外科杂志,1999,37(5)：292-294.
66.翟秀兰,郝美金,刘欣,等.胆囊结石与胆囊动力学相关的研究[J].河北医科大学学报.2007,28(1)：45-46
67.帅建,戴丽萍,佘志红,等.无症状胆囊结石病患者胆囊排空功能的研究[J].海南医学,2006,17(3)：16-17.
68. Catnatch SM,Fairclongh PD,Frembath RC,et al.Effect of oral erythromycin on gallbladder motility in normal subjects and subjects with gallstones [J]. Gastroenterol,1992,102:2071 2076.
69.张继红,杨可桢,韩本立.自制动力散预防胆囊结石形成的实验研究[J].普外基础与临床杂志,1997,4：68-70.
70.章琳,董蕾.高胆固醇饮食对胆囊结石形成和胆囊运动的影响[J].西安交通大学学报(医学版),2005,26(3)：260-262.
71. Dionigi L, Giovanni MMD, Vito M et al.Duodenogastric reflux of bite acids, gasttrin and parietal cells, and gastric acid secretion before and 6 months after cholecystectomy[J]. Am J Surg,1990,159(6):575-578
72.方驰华.腹腔镜胆囊切除术中胆管损伤预防及处理[J].中国实用外科杂志,2007,27(9)：741-743
73. Lum YW, House MG, Hayanga AJ,et al.Postcholecystectomy syndrome in the laparoscopic era [J]. J Laparoendosc Adv Surg Tech A,2006,16(5):482-485.
74.刘建辉,邵青龙,魏银江,等.腹腔镜联合胆道镜保胆取石术的临床研究[J],中国普通外科杂志,2009,18(8)：877-879
75. 许建平,刘衍民,简锋,等.腹腔镜与开腹保胆取石术治疗胆囊结石的对比研究[J].中国微创外科杂志,2009,9(2)：148-150
76. 姚军,杨海明,杨夕柏,等.腹腔镜联合硬性胆道镜保胆取石术的临床观察(附268例报告).中国内镜杂志,2009,15(10)：1107-1108
77. Ding X, Lu CY, Mei Y,et al. Correlation between gene expression of CCK-A receptor and emptying dysfunction of the gallbladder in patients with gallstones and diabetes mellitus[J]. Hepatobiliary Pancreat Dis Int.2005,4(2):295-298.
78、马文丽.医学分子生物学.北京：高等教育出版社,2008：163
79、李金明主编.实时荧光PCR技术.北京：人民军医出版社,2009：14
80.陈凤花,王琳,胡丽华.实时荧光定量RT—PCR内参基因的选择[J].临床检验杂志,2005,23(5)393-395
81. Bustin S A. Quantification of mRNA using real-time reverse transcription PCR (RT-PCR):trends and problems[J].J Mol Endocrinol,2002,29(1):23-39.
82. Goidin D, Mamessier A, Staquet M J, et al. Ribosomal 18S RNA prevails over glyceraldehyde-3-phosphate dehydrogenase and β-actin genes as internal standard for qu an titative comparison of mRNA levels in invasive an d noninvasive human melan onla cell subpopulations[J].Anal Biochem,2001,295(1):17-21.
83. Lupberger J, Kreur K A, Baskayn G, et Quantitative analysis of beta-actin, B2-microglobulin and porphobilinogen deaminase mRNA and their comparison as control transcripts for RT-PCR[J].Mol Cel Probes,2002,16(1):25-30.
84.贺师鹏,胡雅儿,夏宗勤.受体研究技术.北京：北京大学医学出版社,2004：108
85.朱铭岩,王志伟,陈锦鹏,等.胆囊结石患者CCK受体mRNA测定的临床意义[J].肝胆胰外科杂志,2004,16(4)：255-257.62
86.贺师鹏,胡雅儿,夏宗勤.受体研究技术.北京：北京大学医学出版社,2004：260-2
87. Hauters P, de Neve de Roden A, Pour-baix A, et al. Cholelithiasis:a serious complication after total gastrectomy[J]. Br J Surg,1988,75:899-900.
88. El-Salhy M. Neuropeptide levels in murine liver and biliary pathways[J]. Ups J Med Sci,2000,105:207-213.
89. Muramatsu S, Sonobe K, Tohara K, et al. Effect of truncal vagotomy on gallbladder bile kinetics in conscious dogs[J]. Neuro-gastroenterol Motil, 1999,11:357-364.
90. Otsuki M.Pathophysiological role of cholecystokinin in humans[J]. J Gastroenterol Hepatol.2000,15 Suppl:D71-83.
91. Xiao ZL, Chen Q, Biancani P, et al.Mechanisms of gallbladder hypomotility in pregnant guinea pigs[J]. Gastroenterology,1999,116:411-419.
92. Wang HH, Portincasa P, Liu M,et al.Effect of gallbladder hypomotility on cholesterol crystallization and growth in CCK-deficient mice[J]. Biochim Biophys Acta.2010;1801(2):138-146.
93. Miller LJ,Holicky EL,Vlrich CD,et al. Abnornal processing of the human cholecystokinin receptor gene in association with gallstones and obesity [J]. Gastroentorology,1995,109(4):1375-1380
94. 陈瑞新,朱铭岩,王志伟,等.胆囊结石患者胆囊壁CCK-AR mRNA表达及血浆CCK-8水平与胆囊排空功能的关系[J].山东医药,2006,46(36)：1-2
95. Behar J,Lee KY,Thompson W,et al. Gallbladder contraction in patients with pigment,and cholesterol stones[J]. Gastroenterology,1989,97(6):1479-1484.
96. Xiao ZL, Chen Q, Amaral J, Biancani P, Jensen RT, Behar J.CCK receptor dysfunction in muscle membranes from human gallbladders with cholesterol stones[J]. Am J Physiol.1999,276(6 Pt 1):G1401-1407.
97. Upp JR,Neadon WH,Sigh P,et al. Correlation of cholecystokinin re-ceptors with gallbladder contractility in patients with gallstones[J].Ann Surg,1987, 205(6):641-648.
98. Funaki NO,Tanaka J,Ohshio G,et al. Cytokeratin 20 mRNA in pe-ripheral venous blood of colorectal carcinoma patients[J]. Br J Cancer,1998,77(8):1327-1332.
99.朱坚,韩天权,陈胜,等.胆石病患者胆囊收缩素受体与胆囊动力关系的研究-胆囊收缩“正常”与收缩减弱患者的病理改变[J].外科理论与实践,1999,4(1)：36-38.
100.安新,王利民,李琳,等.应用全自动生化分析仪测定人胆汁脂质成分[J].检验医学.2007,22(4)：422-424
101. Ostrow JD, Branham V. Photodecomposition of bilirubin and biliverdin in vitro [J]. Gustrornterology,1970,58(1):15-25.
102. Berk PD, Berlin NI. Chemistry and physiology of bile pigments [M]. Philadelphia:F. A. Davis Company,1977:81-92.
103. Sharma BC, Agarwal DK, Dhiman RK,et al. Bile lithogenicity and gallbladder emptying in patients with microlithiasis:effect of bile acid therapy[J]. Gastroenterology.1998 Jul;115(1):124-8.
104. 黄明文,王刚,傅华群,等.胆汁胆固醇对胆囊平滑肌线粒体及TGF-β1表达的影响[J].中国临床医学,2006,13(5)：750-752
105. Poston GJ,Singh P,Praviam E,et al.Early stages of gallstone formation in guinea pig are associated with decreased biliary sentivity to cholecystokinin [J].Dig Dis Sci,1992,37:1236-1244
106. Chen WL,Wu HW,Jiang MJ. Transforming Growth Factor-betal gene and protein expression associated with atherogenesis of cholesterol-fed rabbits[J].Histol Histopathol,2000,15(2):421-428
107. Miyasaka K, Kanai S, Ohta M, etal.Age-associated gallstone formation in male and female CCK-1(A) receptor-deficient mice. J Gastroenterol[J].2007,42(6): 493-6.
108. Kano M, Shoda J, Satoh S,et al. Increased expression of gallbladder cholecystokinin:a receptor in prairie dogs fed a high-cholesterol diet and its dissociation with decreased contractility in response to cholecystokinin[J]. J Lab Clin Med,2002,139(5):285-294.
109. Xiao Z, Schmitz F, Pricolo VE, Biancani P, Behar J.Role of caveolae in the pathogenesis of cholesterol-induced gallbladder muscle hypomotility[J]. Am J Physiol Gastrointest Liver Physiol.2007,292(6):G1641-1649.
110. Pozo M J, Camello P J, Mawe G M. Chemical mediators of gallbladder dysmotility[J]. Cur Med Chem,2004,11(13):1801-1812.
111. Glasbrenner B, Dominguez-Munoz JE, Nelson DK,et al. Postprandial release of cholecystokinin and pancreatic polypeptide in health and in gallstone disease: relationships with gallbladder contraction [J]. Am J Gastroenterol,1994,89(3): 404-410.
112. Kern F. Effects of dietary cholesterol on cholesterol and bile acid homeostasis in patients with cholesterol gallstones [J]. J Clin Invest,1994,93(3):1186-1194.
113. Chen Q, Amaral J, Biancani P, et al. Excessive membrane cholesterol alters human gallbladder muscle contractility and membrane fluidity [J]. Gastroenterology,1999,116:678-685.
114. Joseph L,Goldsteins, Micheal SB.Progress in under standing the LDL receptor and HMG-CoA Reductase two membrane proteins that regulate the plasma cholesterol [J].J Lipid Res,1984;25:1450-1461
115.李年丰,张阳德,何剪太,等.胆固醇合成限速酶抑制剂普伐他汀对胆囊胆固醇结石患者血液及胆汁中脂类成分的影响[J].中国现代医学杂志,1999,9(5)：14-15
1 Holzbach RT.Nucleation and growth of cholesterol crystals [J].Gastroenterol Clin North Am,1991,20(1):67-84
2 张继红,杨可桢,韩本立.胆囊结石形成的动力学机制[J].中华普通外科杂志,2001,16(7)：424-426.
3 Ikeda Y, Shinchi K, Kono S, et al. Risk of gallstones following gastrectomy in Japanese men [J]. Surg Today,1995,25:515-518.
4 Hauters P, de Neve de Roden A, Pour-baix A, et al. Cholelithiasis:a serious complication after total gastrectomy [J]. Br J Surg,1988,75:899-900.
5 El-Salhy M. Neuropeptide levels in murine liver and biliary pathways [J]. Ups J Med Sci,2000,105:207-213.
6 Muramatsu S, Sonobe K, Tohara K, et al. Effect of truncal vagotomy on gallbladder bile kinetics in conscious dogs [J]. Neuro-gastroenterol Motil, 1999,11:357-364.
7 Luiking YC, Akkermans LM, Peeters TL, et al. Effects of motilin on human interdigestive gastrointestinal and gallbladder motility, and involvement of 5HT3 receptors [J]. Neurogastroenterol Motil,2002,14:151-159.
8 Degen LP, Peng F, Collet A, et al.Blockade of GRP receptors inhibits gastric emptying and gallbladder contraction but accelerates small intestinal transit [J]. Gastroenterology,2001,120:361-368.
9 Veysey MJ, Malcolm P, Mallet Al, et al.Effects of cisapride on gall bladder emptying, intestinal transit, and serum deoxycholate:a prospective, randomised, double blind, placebo controlled trial [J]. Gut,2001,49:828-834.
10 Xiao ZL, Chen Q, Biancani P, et al.Mechanisms of gallbladder hypomotility in pregnant guinea pigs [J]. Gastroenterology,1999,116:411-419.
11 宁殿宾,曹文庆,赵玉哲,等,胆囊结石与胆囊收缩素及其受体的关系研究[J].现代中西医结合杂志,2007,16(9)：1157-1158
12 Glasbrenner B, Dominguez-Munoz JE,et al. Postprandial release of cholecystokinin and pancreatic polypeptide in health and in gallstone disease: relationships with gallbladder contraction [J]. Am J Gasstroenterol.1994, 89(3)：404.
13 刘嘉林,李宁.CCK及CCK受体与胆囊结石的关系[J].国外医学外科学分册,1997,24(4)：211
14 陈瑞新,王志伟,黄健,等.CCK-8在胆石症患者血浆中的水平变化及其临床意义[J].放射免疫学杂志,2004,17(5)：336-337
15 赵虎,张仲才.胆石症患者血清降钙素、基因相关肽、肽YY、胆囊收缩素和前列腺素变化[J].第四军医大学学报,2001,22(15)：1415-1416
16 陈瑞新,朱铭岩,王志伟,等.胆囊结石患者胆囊壁CCK-ARmRNA表达及血浆CCK-8水平与胆囊排空功能的关系[J].山东医药,2006,46(36)：1-2
17 张磊,胡江,梁鲁,等.胆囊功能分级的研究进展.包头医学院学报.2007,23(4)：440-442
18 翟秀兰,郝美金,刘欣,等.胆囊结石与胆囊动力学相关的研究[J].河北医科大学学报.2007,28(1)：45-46
19 胡望明,尹朝礼,王天才,等.肝硬化患者胆囊运动功能的超声研究[J].中国超声医学杂志,1997,13：42-44.
20 Buchpiguel CA, Sapienza MT, Vezzozzo DP, et al. Gallbladder emptying in normal volunteers. Comparative study between cholescintigraphy and ultrasonography [J].Clin Nucl Med,1996,21:208-212.
21 Down RH, Arnold J, Goldin A, et al.Comparison of accuracy of 99mTc-pyridoxylidene glutamate scanning with oral cholecystography and ultrasonography in diagnosis of acute cholecystitis [J]. Lancet,1979,314:1094-1097.
22 Vyas PK, Vesy TL, Konez O, et al. Estimation of gallbladder ejection fraction utilizing cholecystokinin-stimulated magnetic resonance cholangiography and comparison with hepatobiliary scintigraphy [J]. J Magn Reson Imaging,2002, 15:75-81.
23 帅建,张圣道,韩天权,等.胆囊结石病胆囊排空与缩胆囊素受体基因表达关系的研究.中华外科杂志,1999,37(5)：292-294
24帅建,戴丽萍,佘志红,等.无症状胆囊结石病患者胆囊排空功能的研究[J].海南医学,2006,17(3)：16-17
25 Pauletzk J, Paumgartner G. Defects in gallbladder motor function-role in gallstone formation and recurrence[J].Aliment Pharmacol Ther,2000,14(suppl 2):32-34.
26 Pozo M J, Camello P J, Mawe G M. Chemical mediators of gallbladder dysmotility[J]. Cur Med Chem,2004,11(13):1801-1812.
27 章琳,董蕾.高胆固醇饮食对胆囊结石形成和胆囊运动的影响[J].西安交通大学学报(医学版),2005,26(3)：260-262
28 Zhu J,Han TQ,Chen S,et al. Gallbladder motor function,plasma cholecystokinin and cholecystokinin receptor of gallbladder in cholesterol stone patients[J]. World J Gastroenterol,2005,11(11):1685-1689.
29 Ding X,Lu CY,Mei Y,et al. Correlation between gene expression of CCK-A receptor and emptying dysfunction of the gallbladder in patients with gallstones and diabetes mellitus[J]. Hepatobiliary Pancreat Dis Int,2005,4(2):295-298.
30 Behar J,Lee KY,Thompson W,et al. Gallbladder contraction in patients with pigment,and cholesterol stones[J]. Gastroenterology,1989,97(6):1479-1484.
31 Miyasaka K, TaKata Y, Funakoshi A. Association of cholecystokinin A recptor gene polymorphism with cholelithiasis and the molecular mechanisms of this polymorphism [J]. J Gastroenterol,2002,37 (Supple14):102-107.
32 Sato N, Miyasaka K, Suzuki S,et al. Lack of cholecystokinin-A receptor enhanced gallstone formation:a study in CCK-A receptor gene knockout mice[J]. Dig Dis Sci,2003,48(10):1944-1947.
33 朱铭岩,王志伟,陈锦鹏,等.胆囊结石患者CCK受体mRNA测定的临床意义[J].肝胆胰外科杂志,2004,16(4)：255-257
34 朱坚,韩天权,陈胜,等.胆石病患者胆囊收缩素受体与胆囊动力关系的研究-胆囊收缩“正常”与收缩减弱患者的病理改变[J].外科理论与实践,1999,4(1)：36-38.
35 Funaki NO,Tanaka J,Ohshio G,et al. Cytokeratin 20 mRNA in peripheral venous blood of colorectal carcinoma patients[J]. Br J Cancer,1998,77(8):1327-1332.
36 Miller LJ,Holicky EL,Vlrich CD,et al. Abnornal processing of the human cholecystokinin receptor gene in association with gallstones and obesity [J]. Gastroentorology,1995,109(4):1375-1380.
37 Narkone G,Ferber IA,Miller LJ. The integrity of the choleystokinin receptor gene in gallbladder disease and obesity[J]. Hepatology,1995,22(6):1751-1753.
38 Kano M, Shoda J, Satoh S,et al. Increased expression of gallbladder cholecystokinin:a receptor in prairie dogs fed a high-cholesterol diet and its dissociation with decreased contractility in response to cholecystokinin[J]. J Lab Clin Med,2002,139(5):285-294.
39 Pozo M J, Camello P J, Mawe G M. Chemical mediators of gallbladder dysmotility[J]. Cur Med Chem,2004,11(13):1801-1812.
40 Glasbrenner B, Dominguez-Munoz JE, Nelson DK,et al. Postprandial release of cholecystokinin and pancreatic polypeptide in health and in gallstone disease: relationships with gallbladder contraction [J]. Am J Gastroenterol,1994,89(3): 404-410.
41 Xiao ZL, Chen Q, Amaral J,et al.CCK receptor dysfunction in muscle membranes from human gallbladders with cholesterol stones [J]. Am J Physiol, 1999,276:1401-1407.
42 Kern F. Effects of dietary cholesterol on cholesterol and bile acid homeostasis in patients with cholesterol gallstones [J]. J Clin Invest,1994,93(3):1186-1194.
43傅华群,吴伟顶,邹书兵,等.胆汁胆固醇对胆囊收缩素受体表达的影响[J].中华外科杂志,2002,40(10)：786-788.
44 Chen Q, Amaral J, Biancani P, et al. Excessive membrane cholesterol alters human gallbladder muscle contractility and membrane fluidity [J]. Gastroenterology,1999,116:678-685.
2.韩天权,张圣道.胆石病流行病学研究的现状和发展[J].胃肠病学,2003,8(3)：166-168.
3.中华医学会外科学分会胆道外科学组.我国胆石病十年来的变迁[J].中华外科杂志,1995,33(11)：652-658.
4.陈训如.肝胆外科常见疾病导医指南[M].北京：军事医学科学出版社,2000：185
5.陈希纲,刘家奇,彭民浩,等.胆石病临床流行病学调查[J].中华普通外科杂志,2002,17(2)：99-101
6.石景生,任予.我国胆道外科实验外科研究进展[J].中华实验外科杂志,2004,21(12)：1418-1419
7.粱酉,黄太秀,裴晓红,等.荤素膳食与胆石症发病关系的流行病学调查[J].临床肝胆病杂志,1997,13(3)：152-153.
8. Sandier R S, Everhart J E, Donowitz M,et al. The burden of selected digestive diseases in the United States [J]. Gastroenterology,2002,122 (5):150-153.
9.刘衍民,文辉清,目前保留胆囊手术的几个问题[J].中华外科杂志,2008；46(10)：721-723.
10.张阳德,乔铁,冯禹阳,等.内镜微创外科是治愈疾病及保留器官与器官功能的最佳途径-论内镜下保留胆囊取石或摘除息肉[J].中国内镜杂志,2008,14(5)：449-453.
11.王旭,王翔翔,唐彤,等.内镜保胆取石术临床研究现状[J].中国普外基础与临床杂志,2009；16(9)：773-776.
12.张宝善.关于胆囊结石治疗的争论与Langenbuch理论商榷[J].中国医刊,2007,42(5)：322-325.
13.徐立友,宋钊,付廷海,等.623例内镜取石保胆术[J].中华消化外科杂志,2007,6(6)：459-461.
14.刘京山,李晋忠,赵期康,等.纤维胆道镜下胆囊切开取石保胆治疗胆囊结石612例随访结果分析[J].中华外科杂志,2009,47(2)：279-282.
15.邹一平,萧荫祺.保胆取石术有关问题的探讨[J].中华肝胆外科杂 志,2009,15(1)：1-3.
16. vanBerge-Henegouwen GP, Venneman NG, van Erpecum KJ, et al.Drugs affecting biliary lipid secretion and gallbladder motility:their potential role in gallstone treatment and prevention[J]. Curr Drug Targets Immune Endocr Metabol Disord. 2005;5(2):185-91.
17.宁殿宾,曹文庆,赵玉哲,等,胆囊结石与胆囊收缩素及其受体的关系研究[J].现代中西医结合杂志,2007,16(9)：1157-1158.
18. Zhu J,Han TQ,Chen S,et al. Gallbladder motor function,plasma cholecystokinin and cholecystokinin receptor of gallbladder in cholesterol stone patients[J]. World J Gastroenterol,2005,11(11):1685-1689.
19. Miyasaka K, TaKata Y, Funakoshi A. Association of cholecystokinin A recptor gene polymorphism with cholelithiasis and the molecular mechanisms of this polymorphism[J].J Gastroenterol.2002,37 Suppl 14:102-6.
20. Sato N, Miyasaka K, Suzuki S,et al. Lack of cholecystokinin-A receptor enhanced gallstone formation:a study in CCK-A receptor gene knockout mice[J]. Dig Dis Sci,2003,48(10):1944-1947.
21. Miyasaka K, Kanai S, Ohta M, etal.Age-associated gallstone formation in male and female CCK-1(A) receptor-deficient mice[J]. J Gastroenterol.2007,42(6): 493-496.
22. Kano M, Shoda J, Satoh S,et al. Increased expression of gallbladder cholecystokinin:a receptor in prairie dogs fed a high-cholesterol diet and its dissociation with decreased contractility in response to cholecystokinin[J]. J Lab Clin Med,2002,139(5):285-294.
23. Pozo M J, Camello P J, Mawe G M. Chemical mediators of gallbladder dysmotility[J].Cur Med Chem,2004,11(13):1801-1812.
24.傅华群,吴伟顶,邹书兵,等.胆汁胆固醇对胆囊收缩素受体表达的影响[J].中华外科杂志,2002,40(10)：786-788.
25. Pomeranz IS,Shaffer EA.Abnormal gallbladder emptying in a subgroup of patients with gallstones.Gastroentorology[J];1985,88:787
26 Portincasa P, Moschetta A, Colecchia A,et al.Measurements of gallbladder motor function by ultrasonography:towards standardization[J]. Dig Liver Dis.2003,35 Suppl 3:S56-61.
27.陈胜,韩天权,蒋渝,等.胆囊结石患者胆囊动力学紊乱机制的研究[J].中华外科杂志,1998,36：14.
28. Meltzer D,Egleston B. How patients with diabetes perceive their risk for major complications[J]. Eff Clin Pract,2000,3(1):7-25
29. Okada N, Kuboto A, Imamura T,et al. Evalution of cholecys-tokinin, gastrin, CCK-A receptor and sCCK-8 gastrin receptor gene expression in gastric cancer[J]. Cancer Lett.1996,106(2):257-260.
30. Duellberg SH, Werneck-Silva AL, Sipahy AM,et al. Cholesterol gallstone formation:supersaturation, nucleation and gallbladder motility[J].Rev Hosp Clin Fac Med Sao Paulo.1996,51(5):198-202.
31. Wang HH,Portincasa P,Wang DQ.Molecular pathophysiology and physical chemistry of cholesterol gallstones[J].Front Bios-ci,2008,13(4):401-423.
32.赵纪春,舒哗,程南生,等.胆囊结石中胆固醇代谢变化的实验研究[J].中国普通外科杂志,2000,9：124-126
33.韩天权,蒋兆彦,张圣道.胆结石成因研究进展[J].中国实用外科杂志,2001,21：123-125.
34. Admirand WH. Small DM.The physiochemical basis of cholesterol gallstone formation inman[J]. JClin Invest,1968,47(5):1043-1052.
35. Prigun NP, Korolevich AN. Changes in hu-man biliary vesicle sizes in pathological states [J].Biofizika,2002,47:1095
36. Portincasa P,Venneman NG,Moschetta A, et al. Quantitation of cholesterol crystallization from supersaturated model bile [J]. J Lipid Res,2002,43:604
37. Venneman NG,Huisman SJ,Moschetta A, et al. Effects of hydrophobic and hydrophilic bile salt mixtures on cholesterol crystallization in model biles[J]. Biochim Biophys Acta,2002,1583:221
38. Moschetta A, Vanberge-henegouwen GP,Portincasa P, et al. Cholesterol crystalliza-tion in model biles:effects of bile salt and phospholipid species composition [J]. J Lipid Res,2001,42:1273
39. Sakomoto M,Tazuma S,Chayama K. Less hydrophobic phosphatidylcholine species simplify bil-iary vesicle morphology, but induce bile metastability with a broad spectrum of crystal forms [J]. Biochem J,2002,362:105
40. Gantz DL,Wang DQ,Garey MC, et al. Cryo-electron microscopy of a nucleating model bile in vitreous ice:formation of primordial vesicles [J]. Biophys J, 1999,76:1436
41.吴杰,周建莉,瞿新刚,等.胆汁中各主要有机成分在胆囊结石形成过程中的作用[J].昆明医学院学报,2005,26(4)：4-7.
42. Jiang ZY,Parini P,Eggertsen G,et al.Increased expression of LXR alpha, ABCG5, ABCG8,and SR-BI in the liver from nor-molipidemic,nonobese Chinese gallstone patients[J].J Lipid Res,2008,49(2):464-472.
43.王勇,韩天权,费健,等.胆囊黏膜ABCG5和ABCG8基因在胆固醇结石病中的作用[J].中华实验外科杂志,2007,24(1)：51-52.
44. Behar J. Clinical aspects of gallbladder motor function and dysfunction[J]. Curr Gastroenterol Rep.1999,1(2):91-94.
45. 张继红,杨可桢,韩本立.胆囊结石形成的动力学机制[J].中华普通外科杂志,2001,16(7)：424-426.
46. Jiang ZY,Jiang CY,Wang L,et al.Increased NPC1L1 and ACAT2 expression in the jejunal mucosa from Chinese gallstone patients [J].Biochem Biophys Res Commun,2009,379(1):49-54.
47. Maurer KJ,Rao VP,Ge Z,et al.T-cell function is critical for murine cholesterol gallstone formation[J].Gastroenterology,2007,133(4):1304-1315.
48. Maurer KJ,Carey MC,Fox JGRoles of infection,inflammations, and the immune system in cholesterol gallstone formation[J].Gastroenterology,2009,136(2): 425-440.
49. Maurer KJ,Ihrig MM,Rogers AB,et al.Identification of chole-lithogenic enterohepatic helicobacter species and their role in murine cholesterol gallstone formation[J].Gastroenterology,2005,128(4):1023-1033.
50. 田志杰,韩天权,姜志宏,等.胆囊结石病胆道系统螺杆菌DNA的研究[J].中国实用外科杂志,2004,24(2)：84-87.
51. 郑启昌,魏斌,胡佑化.胆道高压对Oddi括约肌动力学的影响[J].中国病理生理杂志1998,14(5)：469.
52.施维锦.胆道外科学[M].上海：科学技术出版社,1993.27.
53. Rajan M, Wali JP, Sharma MP,et al. Ultrasonographic assessment of gall bladder kinetics in the elderly[J].Indian J Gastroenterol.2000;19(4):158-60.
54. Stads S, Venneman NG, Scheffer RC, et al.Evaluation of gallbladder motility: comparison of two-dimensional and three-dimensional ultrasonography[J]. Ann Hepatol.2007,6(3):164-169.
55. Pallotta N.Ultrasonography in the assessment of gallbladder motor activity[J]. Dig Liver Dis.2003,35 Suppl 3:S67-69.
56. Buchpiguel CA, Sapienza MT, Vezzozzo DP, et al. Gallbladder emptying in normal volunteers. Comparative study between cholescintigraphy and ultrasonography[J].Clin Nucl Med,1996,21:208-212.
57. Down RH, Arnold J, Goldin A, et al.Comparison of accuracy of 99mTc-pyridoxylidene glutamate scanning with oral cholecystography and ultrasonography in diagnosis of acute cholecystitis[J].Lancet,1979,314: 1094-1097.
58. Vyas PK, Vesy TL, Konez O, et al. Estimation of gallbladder ejection fraction utilizing cholecystokinin-stimulated magnetic resonance cholangiography and comparison with hepatobiliary scintigraphy[J]. J Magn Reson Imaging,2002, 15:75-81.
59. Ding X, Gong JP, Lu CY,et al. Relation of abnormal gallbladder arterioles to gallbladder emptying in patients with gallstone and diabetes mellitus[J]. Hepatobiliary Pancreat Dis Int.2004,3(2):275-8.
60.叶生爱,汤文浩.胆囊在胆固醇结石形成中的作用研究进展[J].国外医学外科学分册,2001,28(4)：222-224.
61. Portincasa P, Di Ciaula A, Vendemiale G, et al.Gallbladder motility and cholesterol crystallization in bile from patients with pigment and cholesterol gallstones[J]. Eur J Clin Invest.2000,30(4):317-324.
62. Montet JC, Caroli-Bosc FX, Ferrari P,et al.Gallbladder motility and gut hormone plasma levels in subjects with and without gallstones[J]. Gastroenterol Clin Biol.2005,29(5):569-72.
63. Pauletzk J, Paumgartner G. Defects in gallbladder motfunction-role in gallstone formation and recurrence [J].Aliment Pharmacol Ther,2000,14(suppl 2):32-34.
64 Cerci SS, Ozbek FM, Cerci C,et al.Gallbladder function and dynamics of bile flow in asymptomatic gallstone disease[J]. World J Gastroenterol.2009, 15(22):2763-2767.
65. 帅建,张圣道,韩天权,等.胆囊结石病胆囊排空与缩胆囊素受体基因表达关系的研究[J].中华外科杂志,1999,37(5)：292-294.
66.翟秀兰,郝美金,刘欣,等.胆囊结石与胆囊动力学相关的研究[J].河北医科大学学报.2007,28(1)：45-46
67.帅建,戴丽萍,佘志红,等.无症状胆囊结石病患者胆囊排空功能的研究[J].海南医学,2006,17(3)：16-17.
68. Catnatch SM,Fairclongh PD,Frembath RC,et al.Effect of oral erythromycin on gallbladder motility in normal subjects and subjects with gallstones [J]. Gastroenterol,1992,102:2071 2076.
69.张继红,杨可桢,韩本立.自制动力散预防胆囊结石形成的实验研究[J].普外基础与临床杂志,1997,4：68-70.
70.章琳,董蕾.高胆固醇饮食对胆囊结石形成和胆囊运动的影响[J].西安交通大学学报(医学版),2005,26(3)：260-262.
71. Dionigi L, Giovanni MMD, Vito M et al.Duodenogastric reflux of bite acids, gasttrin and parietal cells, and gastric acid secretion before and 6 months after cholecystectomy[J]. Am J Surg,1990,159(6):575-578
72.方驰华.腹腔镜胆囊切除术中胆管损伤预防及处理[J].中国实用外科杂志,2007,27(9)：741-743
73. Lum YW, House MG, Hayanga AJ,et al.Postcholecystectomy syndrome in the laparoscopic era [J]. J Laparoendosc Adv Surg Tech A,2006,16(5):482-485.
74.刘建辉,邵青龙,魏银江,等.腹腔镜联合胆道镜保胆取石术的临床研究[J],中国普通外科杂志,2009,18(8)：877-879
75. 许建平,刘衍民,简锋,等.腹腔镜与开腹保胆取石术治疗胆囊结石的对比研究[J].中国微创外科杂志,2009,9(2)：148-150
76. 姚军,杨海明,杨夕柏,等.腹腔镜联合硬性胆道镜保胆取石术的临床观察(附268例报告).中国内镜杂志,2009,15(10)：1107-1108
77. Ding X, Lu CY, Mei Y,et al. Correlation between gene expression of CCK-A receptor and emptying dysfunction of the gallbladder in patients with gallstones and diabetes mellitus[J]. Hepatobiliary Pancreat Dis Int.2005,4(2):295-298.
78、马文丽.医学分子生物学.北京：高等教育出版社,2008：163
79、李金明主编.实时荧光PCR技术.北京：人民军医出版社,2009：14
80.陈凤花,王琳,胡丽华.实时荧光定量RT—PCR内参基因的选择[J].临床检验杂志,2005,23(5)393-395
81. Bustin S A. Quantification of mRNA using real-time reverse transcription PCR (RT-PCR):trends and problems[J].J Mol Endocrinol,2002,29(1):23-39.
82. Goidin D, Mamessier A, Staquet M J, et al. Ribosomal 18S RNA prevails over glyceraldehyde-3-phosphate dehydrogenase and β-actin genes as internal standard for qu an titative comparison of mRNA levels in invasive an d noninvasive human melan onla cell subpopulations[J].Anal Biochem,2001,295(1):17-21.
83. Lupberger J, Kreur K A, Baskayn G, et Quantitative analysis of beta-actin, B2-microglobulin and porphobilinogen deaminase mRNA and their comparison as control transcripts for RT-PCR[J].Mol Cel Probes,2002,16(1):25-30.
84.贺师鹏,胡雅儿,夏宗勤.受体研究技术.北京：北京大学医学出版社,2004：108
85.朱铭岩,王志伟,陈锦鹏,等.胆囊结石患者CCK受体mRNA测定的临床意义[J].肝胆胰外科杂志,2004,16(4)：255-257.62
86.贺师鹏,胡雅儿,夏宗勤.受体研究技术.北京：北京大学医学出版社,2004：260-2
87. Hauters P, de Neve de Roden A, Pour-baix A, et al. Cholelithiasis:a serious complication after total gastrectomy[J]. Br J Surg,1988,75:899-900.
88. El-Salhy M. Neuropeptide levels in murine liver and biliary pathways[J]. Ups J Med Sci,2000,105:207-213.
89. Muramatsu S, Sonobe K, Tohara K, et al. Effect of truncal vagotomy on gallbladder bile kinetics in conscious dogs[J]. Neuro-gastroenterol Motil, 1999,11:357-364.
90. Otsuki M.Pathophysiological role of cholecystokinin in humans[J]. J Gastroenterol Hepatol.2000,15 Suppl:D71-83.
91. Xiao ZL, Chen Q, Biancani P, et al.Mechanisms of gallbladder hypomotility in pregnant guinea pigs[J]. Gastroenterology,1999,116:411-419.
92. Wang HH, Portincasa P, Liu M,et al.Effect of gallbladder hypomotility on cholesterol crystallization and growth in CCK-deficient mice[J]. Biochim Biophys Acta.2010;1801(2):138-146.
93. Miller LJ,Holicky EL,Vlrich CD,et al. Abnornal processing of the human cholecystokinin receptor gene in association with gallstones and obesity [J]. Gastroentorology,1995,109(4):1375-1380
94. 陈瑞新,朱铭岩,王志伟,等.胆囊结石患者胆囊壁CCK-AR mRNA表达及血浆CCK-8水平与胆囊排空功能的关系[J].山东医药,2006,46(36)：1-2
95. Behar J,Lee KY,Thompson W,et al. Gallbladder contraction in patients with pigment,and cholesterol stones[J]. Gastroenterology,1989,97(6):1479-1484.
96. Xiao ZL, Chen Q, Amaral J, Biancani P, Jensen RT, Behar J.CCK receptor dysfunction in muscle membranes from human gallbladders with cholesterol stones[J]. Am J Physiol.1999,276(6 Pt 1):G1401-1407.
97. Upp JR,Neadon WH,Sigh P,et al. Correlation of cholecystokinin re-ceptors with gallbladder contractility in patients with gallstones[J].Ann Surg,1987, 205(6):641-648.
98. Funaki NO,Tanaka J,Ohshio G,et al. Cytokeratin 20 mRNA in pe-ripheral venous blood of colorectal carcinoma patients[J]. Br J Cancer,1998,77(8):1327-1332.
99.朱坚,韩天权,陈胜,等.胆石病患者胆囊收缩素受体与胆囊动力关系的研究-胆囊收缩“正常”与收缩减弱患者的病理改变[J].外科理论与实践,1999,4(1)：36-38.
100.安新,王利民,李琳,等.应用全自动生化分析仪测定人胆汁脂质成分[J].检验医学.2007,22(4)：422-424
101. Ostrow JD, Branham V. Photodecomposition of bilirubin and biliverdin in vitro [J]. Gustrornterology,1970,58(1):15-25.
102. Berk PD, Berlin NI. Chemistry and physiology of bile pigments [M]. Philadelphia:F. A. Davis Company,1977:81-92.
103. Sharma BC, Agarwal DK, Dhiman RK,et al. Bile lithogenicity and gallbladder emptying in patients with microlithiasis:effect of bile acid therapy[J]. Gastroenterology.1998 Jul;115(1):124-8.
104. 黄明文,王刚,傅华群,等.胆汁胆固醇对胆囊平滑肌线粒体及TGF-β1表达的影响[J].中国临床医学,2006,13(5)：750-752
105. Poston GJ,Singh P,Praviam E,et al.Early stages of gallstone formation in guinea pig are associated with decreased biliary sentivity to cholecystokinin [J].Dig Dis Sci,1992,37:1236-1244
106. Chen WL,Wu HW,Jiang MJ. Transforming Growth Factor-betal gene and protein expression associated with atherogenesis of cholesterol-fed rabbits[J].Histol Histopathol,2000,15(2):421-428
107. Miyasaka K, Kanai S, Ohta M, etal.Age-associated gallstone formation in male and female CCK-1(A) receptor-deficient mice. J Gastroenterol[J].2007,42(6): 493-6.
108. Kano M, Shoda J, Satoh S,et al. Increased expression of gallbladder cholecystokinin:a receptor in prairie dogs fed a high-cholesterol diet and its dissociation with decreased contractility in response to cholecystokinin[J]. J Lab Clin Med,2002,139(5):285-294.
109. Xiao Z, Schmitz F, Pricolo VE, Biancani P, Behar J.Role of caveolae in the pathogenesis of cholesterol-induced gallbladder muscle hypomotility[J]. Am J Physiol Gastrointest Liver Physiol.2007,292(6):G1641-1649.
110. Pozo M J, Camello P J, Mawe G M. Chemical mediators of gallbladder dysmotility[J]. Cur Med Chem,2004,11(13):1801-1812.
111. Glasbrenner B, Dominguez-Munoz JE, Nelson DK,et al. Postprandial release of cholecystokinin and pancreatic polypeptide in health and in gallstone disease: relationships with gallbladder contraction [J]. Am J Gastroenterol,1994,89(3): 404-410.
112. Kern F. Effects of dietary cholesterol on cholesterol and bile acid homeostasis in patients with cholesterol gallstones [J]. J Clin Invest,1994,93(3):1186-1194.
113. Chen Q, Amaral J, Biancani P, et al. Excessive membrane cholesterol alters human gallbladder muscle contractility and membrane fluidity [J]. Gastroenterology,1999,116:678-685.
114. Joseph L,Goldsteins, Micheal SB.Progress in under standing the LDL receptor and HMG-CoA Reductase two membrane proteins that regulate the plasma cholesterol [J].J Lipid Res,1984;25:1450-1461
115.李年丰,张阳德,何剪太,等.胆固醇合成限速酶抑制剂普伐他汀对胆囊胆固醇结石患者血液及胆汁中脂类成分的影响[J].中国现代医学杂志,1999,9(5)：14-15
1 Holzbach RT.Nucleation and growth of cholesterol crystals [J].Gastroenterol Clin North Am,1991,20(1):67-84
2 张继红,杨可桢,韩本立.胆囊结石形成的动力学机制[J].中华普通外科杂志,2001,16(7)：424-426.
3 Ikeda Y, Shinchi K, Kono S, et al. Risk of gallstones following gastrectomy in Japanese men [J]. Surg Today,1995,25:515-518.
4 Hauters P, de Neve de Roden A, Pour-baix A, et al. Cholelithiasis:a serious complication after total gastrectomy [J]. Br J Surg,1988,75:899-900.
5 El-Salhy M. Neuropeptide levels in murine liver and biliary pathways [J]. Ups J Med Sci,2000,105:207-213.
6 Muramatsu S, Sonobe K, Tohara K, et al. Effect of truncal vagotomy on gallbladder bile kinetics in conscious dogs [J]. Neuro-gastroenterol Motil, 1999,11:357-364.
7 Luiking YC, Akkermans LM, Peeters TL, et al. Effects of motilin on human interdigestive gastrointestinal and gallbladder motility, and involvement of 5HT3 receptors [J]. Neurogastroenterol Motil,2002,14:151-159.
8 Degen LP, Peng F, Collet A, et al.Blockade of GRP receptors inhibits gastric emptying and gallbladder contraction but accelerates small intestinal transit [J]. Gastroenterology,2001,120:361-368.
9 Veysey MJ, Malcolm P, Mallet Al, et al.Effects of cisapride on gall bladder emptying, intestinal transit, and serum deoxycholate:a prospective, randomised, double blind, placebo controlled trial [J]. Gut,2001,49:828-834.
10 Xiao ZL, Chen Q, Biancani P, et al.Mechanisms of gallbladder hypomotility in pregnant guinea pigs [J]. Gastroenterology,1999,116:411-419.
11 宁殿宾,曹文庆,赵玉哲,等,胆囊结石与胆囊收缩素及其受体的关系研究[J].现代中西医结合杂志,2007,16(9)：1157-1158
12 Glasbrenner B, Dominguez-Munoz JE,et al. Postprandial release of cholecystokinin and pancreatic polypeptide in health and in gallstone disease: relationships with gallbladder contraction [J]. Am J Gasstroenterol.1994, 89(3)：404.
13 刘嘉林,李宁.CCK及CCK受体与胆囊结石的关系[J].国外医学外科学分册,1997,24(4)：211
14 陈瑞新,王志伟,黄健,等.CCK-8在胆石症患者血浆中的水平变化及其临床意义[J].放射免疫学杂志,2004,17(5)：336-337
15 赵虎,张仲才.胆石症患者血清降钙素、基因相关肽、肽YY、胆囊收缩素和前列腺素变化[J].第四军医大学学报,2001,22(15)：1415-1416
16 陈瑞新,朱铭岩,王志伟,等.胆囊结石患者胆囊壁CCK-ARmRNA表达及血浆CCK-8水平与胆囊排空功能的关系[J].山东医药,2006,46(36)：1-2
17 张磊,胡江,梁鲁,等.胆囊功能分级的研究进展.包头医学院学报.2007,23(4)：440-442
18 翟秀兰,郝美金,刘欣,等.胆囊结石与胆囊动力学相关的研究[J].河北医科大学学报.2007,28(1)：45-46
19 胡望明,尹朝礼,王天才,等.肝硬化患者胆囊运动功能的超声研究[J].中国超声医学杂志,1997,13：42-44.
20 Buchpiguel CA, Sapienza MT, Vezzozzo DP, et al. Gallbladder emptying in normal volunteers. Comparative study between cholescintigraphy and ultrasonography [J].Clin Nucl Med,1996,21:208-212.
21 Down RH, Arnold J, Goldin A, et al.Comparison of accuracy of 99mTc-pyridoxylidene glutamate scanning with oral cholecystography and ultrasonography in diagnosis of acute cholecystitis [J]. Lancet,1979,314:1094-1097.
22 Vyas PK, Vesy TL, Konez O, et al. Estimation of gallbladder ejection fraction utilizing cholecystokinin-stimulated magnetic resonance cholangiography and comparison with hepatobiliary scintigraphy [J]. J Magn Reson Imaging,2002, 15:75-81.
23 帅建,张圣道,韩天权,等.胆囊结石病胆囊排空与缩胆囊素受体基因表达关系的研究.中华外科杂志,1999,37(5)：292-294
24帅建,戴丽萍,佘志红,等.无症状胆囊结石病患者胆囊排空功能的研究[J].海南医学,2006,17(3)：16-17
25 Pauletzk J, Paumgartner G. Defects in gallbladder motor function-role in gallstone formation and recurrence[J].Aliment Pharmacol Ther,2000,14(suppl 2):32-34.
26 Pozo M J, Camello P J, Mawe G M. Chemical mediators of gallbladder dysmotility[J]. Cur Med Chem,2004,11(13):1801-1812.
27 章琳,董蕾.高胆固醇饮食对胆囊结石形成和胆囊运动的影响[J].西安交通大学学报(医学版),2005,26(3)：260-262
28 Zhu J,Han TQ,Chen S,et al. Gallbladder motor function,plasma cholecystokinin and cholecystokinin receptor of gallbladder in cholesterol stone patients[J]. World J Gastroenterol,2005,11(11):1685-1689.
29 Ding X,Lu CY,Mei Y,et al. Correlation between gene expression of CCK-A receptor and emptying dysfunction of the gallbladder in patients with gallstones and diabetes mellitus[J]. Hepatobiliary Pancreat Dis Int,2005,4(2):295-298.
30 Behar J,Lee KY,Thompson W,et al. Gallbladder contraction in patients with pigment,and cholesterol stones[J]. Gastroenterology,1989,97(6):1479-1484.
31 Miyasaka K, TaKata Y, Funakoshi A. Association of cholecystokinin A recptor gene polymorphism with cholelithiasis and the molecular mechanisms of this polymorphism [J]. J Gastroenterol,2002,37 (Supple14):102-107.
32 Sato N, Miyasaka K, Suzuki S,et al. Lack of cholecystokinin-A receptor enhanced gallstone formation:a study in CCK-A receptor gene knockout mice[J]. Dig Dis Sci,2003,48(10):1944-1947.
33 朱铭岩,王志伟,陈锦鹏,等.胆囊结石患者CCK受体mRNA测定的临床意义[J].肝胆胰外科杂志,2004,16(4)：255-257
34 朱坚,韩天权,陈胜,等.胆石病患者胆囊收缩素受体与胆囊动力关系的研究-胆囊收缩“正常”与收缩减弱患者的病理改变[J].外科理论与实践,1999,4(1)：36-38.
35 Funaki NO,Tanaka J,Ohshio G,et al. Cytokeratin 20 mRNA in peripheral venous blood of colorectal carcinoma patients[J]. Br J Cancer,1998,77(8):1327-1332.
36 Miller LJ,Holicky EL,Vlrich CD,et al. Abnornal processing of the human cholecystokinin receptor gene in association with gallstones and obesity [J]. Gastroentorology,1995,109(4):1375-1380.
37 Narkone G,Ferber IA,Miller LJ. The integrity of the choleystokinin receptor gene in gallbladder disease and obesity[J]. Hepatology,1995,22(6):1751-1753.
38 Kano M, Shoda J, Satoh S,et al. Increased expression of gallbladder cholecystokinin:a receptor in prairie dogs fed a high-cholesterol diet and its dissociation with decreased contractility in response to cholecystokinin[J]. J Lab Clin Med,2002,139(5):285-294.
39 Pozo M J, Camello P J, Mawe G M. Chemical mediators of gallbladder dysmotility[J]. Cur Med Chem,2004,11(13):1801-1812.
40 Glasbrenner B, Dominguez-Munoz JE, Nelson DK,et al. Postprandial release of cholecystokinin and pancreatic polypeptide in health and in gallstone disease: relationships with gallbladder contraction [J]. Am J Gastroenterol,1994,89(3): 404-410.
41 Xiao ZL, Chen Q, Amaral J,et al.CCK receptor dysfunction in muscle membranes from human gallbladders with cholesterol stones [J]. Am J Physiol, 1999,276:1401-1407.
42 Kern F. Effects of dietary cholesterol on cholesterol and bile acid homeostasis in patients with cholesterol gallstones [J]. J Clin Invest,1994,93(3):1186-1194.
43傅华群,吴伟顶,邹书兵,等.胆汁胆固醇对胆囊收缩素受体表达的影响[J].中华外科杂志,2002,40(10)：786-788.
44 Chen Q, Amaral J, Biancani P, et al. Excessive membrane cholesterol alters human gallbladder muscle contractility and membrane fluidity [J]. Gastroenterology,1999,116:678-685.