胆汁中胆固醇升高通过影响CCK-1R再分布抑制胆囊收缩

Increased bile cholesterol content inhibits gallbladder contraction by affecting the re-distribution of CCK-1R

目的分析胆汁总胆固醇含量与胆囊收缩功能的关系,并探讨其可能的机制。方法从2013年3月至2014年1月收集73例在北京协和医院基本外科行胆系手术的胆囊结石患者(结石组)和非胆囊结石患者(非结石组)胆汁,测定胆汁中总胆固醇(TC)和总胆汁酸(TBA)含量。对胆囊结石患者术前行胆囊功能试验。用免疫组化方法测定胆囊黏膜和肌层中I型胆囊收缩素受体(CCK-1R)和细胞膜结构蛋白小窝蛋白-3(Cav-3)的表达。用免疫荧光法定位二者在胆囊黏膜和肌层中的共表达。结果胆囊结石患者胆汁中TC及TBA含量显著高于非结石患者(P<0.05)。胆囊收缩功能较差的患者胆汁中TC含量明显高于收缩功能较好的患者(P<0.05)。结石组胆囊黏膜中Cav-3的表达量明显高于非结石组(P<0.05)。在结石组中CCK-1R和Cav-3在胆囊黏膜和肌层中均有明显共表达,而在非结石组则无明显的共表达现象。结论胆汁中TC含量升高可抑制胆囊收缩功能,其机制与胆囊黏膜和肌层中过多的Cav-3和CCK-1R结合进而影响CCK功能有关。

Objective To analyze the relationship between bile total cholesterol （TC） content and the contraction of the gallbladder,and to explore its possible mechanism.Methods A total of 73 patients with or without gallstones,who underwent biliary surgery in the Department of General Surgery in PUMCH from March 2013 to January 2014,were selected and divided into gallstone group and non-gallstone group.The bile of all these patients was collected during the operation,and the content of the bile TC and total bile acid （TBA） was detected.The gallbladder contraction test in patients with gallstones was performed before the surgery.The expression of cholecystokinin-1 receptor （CCK-1 R） and caveolin-3 （Cav-3） in gallbladder mucosa and the smooth muscle in two groups was detected using immunohistochemistry staining method.The co-localization of CCK-1R and Cav-3 in gallbladder mucosa and the smooth muscle in two groups was also observed using immunofluorescence method.Results The content of bile TC and TBA in patients with gallstones was significantly higher than that in patients without gallstones （P 〈 0.05）.The bile TC content in patients with a worse contraction of the gallbladder was significantly higher than that in patients with a better contraction of the gallbladder （P 〈 0.05）.The immunohistochemistry staining revealed that the expression of Cav-3 in the gallbladder mucosa in gallstone group was significantly higher than that in non-gallstone group （P 〈0.05）.The co-localization of CCK-1R and Cav-3 in gallstone groups was obvious in both gallbladder mucosa and the smooth muscle,while no obvious co-localization was observed in non-gallstone group.Conclusions The increased bile TC content can inhibit the contraction of the gallbladder,and the mechanism may be related to excess Cav-3 binding with CCK-1R,thus affecting the function of CCK.