胆囊切除术后腹泻相关原因的研究进展

1、胆囊切除术后腹泻相关原因的研究进展冯其贞1 李建军*（济宁医学院临床学院，山东 济宁 ，272067）摘要 胆囊结石在我国发病率较高，是临床常见疾病。目前胆囊结石的主要治疗手段仍然是胆囊切除术。随着胆囊切除手术例数的增加，胆囊切除术后不良反应（又称胆囊切除术后综合征）也引起了广泛的关注。胆囊切除术后综合征以腹泻最为常见，它不但直接影响患者的生活质量，还导致结肠癌发病率的升高。所以正确认识胆囊切除术后腹泻的原因十分必要。本文从不同角度对胆囊切除术后腹泻的原因进行归纳、分析，以期为预防及治疗胆囊切除术后腹泻提供指导。关键词 胆囊切除术；胆囊切除术后综合征；腹泻中途分类号 R657.4+2The P

2、rogresses of the Related Factors of the Postcholecystectomy DiarrheaFeng Qizhen1; Li Jianjun*(Jining Medical College, Jining Shandong, 272067)Abstract Cholecystolithiasisis a common disease with a high morbidity in China whose main treatment is still cholecystectomy at present. With the accumulation

3、 of cholecystectomy surgery cases, adverse reactions after cholecystectomy which has also been called the postcholecystectomy syndrome have got a lot of attention. Diarrhea the most common syptom of postcholecystectomy syndrome not only directly affects the quality of patientslife, but also leads to

4、 increased incidence of colon cancer. Thus it is quite necessary to fully understand the causes of postcholecystectomy diarrhea. We summarized and analyzed the possible causes of psotcholecystectomy diarrhea from different aspects hoping to provide some guidances to the prevention and treatment of p

5、sotcholecystectomy diarrhea.Key Words Cholecystectomy; Postcholecystectomy Syndrome; Diarrhea胆囊结石在临床病例中较为常见，发病率高，目前胆囊切除术仍是治疗胆囊结石的首选治疗手段，其术后的不良反应也随着病例数的增加越来越受关注。据基金项目：山东省青少年教育科学研究课题（14BSH216）；山东省青少年教育科学研究课题评审办公室作者单位：济宁医学院临床学院，山东 济宁 272067通讯作者：李建军，Email：lixv16有关文献报道，胆囊切除术后综合征的发生率约为12%-47%1,2。临床表现以疼痛和非

6、疼痛症状为主，分别约占25%和43%。在非疼痛症状中，以腹泻症状最为常见3。胆囊切除术后腹泻发生率各家报道不一，Sand报告为15%，且胆囊切除术后腹泻发生率高、持续时间长、难以治疗4。另有资料证明，胆囊切除术后腹泻是近端结肠癌的危险因素之一5。所以，明确胆囊切除术后导致腹泻的相关原因具有重要的意义。胆囊切除术后出现腹泻的原因争议很大，可能与胆囊功能、胆汁成分、患者个体状态、神经内分泌等因素有关。1、胆囊功能的影响胆囊切除术后初期，胆管还没有来得及代偿，肝脏产生的胆汁直接排至肠道，而进食后只有少量胆汁酸盐排入肠道，脂类的乳化、吸收不全在肠腔堆积致渗透性脂泻。胆囊切除约3个月后，胆管代偿，替代了

7、部分胆囊功能，胆汁的排出具有节律性，类脂的消化与吸收较前充分腹泻减轻。孙诚谊等6认为，胆囊功能的丧失直接导致了慢性腹泻，近端结肠癌、胰腺癌、肝细胞癌、食管腺癌发病率升高。邹大中等研究胆囊排空率与患者术后腹泻发生的相关性，认为以胆囊排空率45%为界限，术前测得胆囊排空率大于或等于45%的患者术后腹泻发生率相对较高，与此相反，术前胆囊排空率小于45%的患者术后腹泻的发生率相对较低，并存在明显差异性7。术前胆囊排空率越高，所反映出的胆囊功能越好，切除胆囊后，其功能的突然缺失，使机体不能完全代偿，故术后腹泻率就相对较高。胆囊浓缩功能的丧失也是腹泻发生的原因之一，肝脏每天分泌800-1200ml胆汁，失

8、去胆囊浓缩功能后，过多的水分进入肠道，引起腹泻。2、胆汁成分的影响Barkun等报道8，由于胆汁酸盐吸收不良所导致的腹泻，占所有腹泻的30%-70%。胆汁酸盐吸收障碍，导致腹泻这一现象，在1967年被首次报道9。Nolan等通过临床对照试验发现，胆囊切除术后患者以及胆汁酸吸收障碍患者纤维母细胞生长因子19（FGF19）较正常人群明显减少。FGF19在胆汁酸盐的合成过程中起到负反馈调节的作用，持续低水平的FGF19致使肝脏不断合成胆汁酸，超出了回肠回吸收胆汁酸的最大限度，产生胆汁酸型腹泻10。另有观点认为，胆囊切除术后的患者，一方面，胆汁的排放节律失调，使胆盐过多进入结肠，胆汁本身即有促使结肠蠕

9、动加快的作用，从而使过多的水分快速通过结肠而出现水样便；再者，肠腔内的厌氧菌作用于排入结肠的胆盐，使之羟基化成双羟胆酸，后者不仅促进肠蠕动，还能抑制结肠对水分的吸收，加剧腹泻11。有学者还认为，通过粪便丢失大量胆盐时也可引起腹泻12。这一观点也被术后腹泻患者粪便中胆汁酸盐成分明显高于对照组这一事实所证明 13。3、患者的个体状态Fisher等14认为胆囊切除术后腹泻与患者年龄及体重指数有明确的相关性。高龄患者胆囊切除术后腹泻的发生率远远低于中青年，分析其可能原因： 一是年轻人相对老年人进食油腻性食物的量及频率较高。二是老年人由于机体各器官功能均有不同程度的衰退，胆囊功能在其衰退过程中，部分被胆

10、管代偿，而中青年患者这种代偿功能较差，机体对胆囊功能的依赖性大，胆囊切除后伴随胆囊功能的丧失，进食含油性食物时，机体很难在短时间内释放足量胆盐，食物中的脂肪消化及吸收障碍，引起脂肪性腹泻。体重指数高的患者比体重指数低的患者发生腹泻的概率较高。 Yueh等15认为术前腹泻、胃肠功能紊乱、性格缺陷、药物的影响、不洁饮食、高脂膳食等都可能是胆囊切除术后出现腹泻的原因。术前无腹泻的患者当中，小于45岁者，胆囊切除后出现腹泻的明显增多，且男性胆囊切除后较女性胆囊切除后出现腹泻的可能性大。建议年龄小于等于45周岁的男性，在行胆囊切除术后1周内进食低脂饮食，以避免腹泻的发生。另有研究发现，切除胆囊会使患者肠

11、道内的菌群失调，一方面表现为有益菌的减少，如双歧杆菌、乳酸杆菌等；另一方面表现为有害机体的细菌增多，如大肠埃希菌、肠球菌等。从肠道菌群平衡的角度解释了胆囊切除术后发生腹泻的可能机制。4、神经内分泌因素目前已发现的脑肠肽约有40多种，多种与胆囊切除术后的腹泻相关，主要有VIP、CCK、5-HT等。41、VIP（Vasoactive Intestinal Peptide, VIP）血管活性肠肽又名舒血管肠肽，在胃肠道中含量最高，能促进胆汁、小肠电解质和水的分泌，诱发肠道动力增强16。有报道胆囊切除术后VIP水平升高可导致腹泻 。42、5-HT（5-hydroxytryptamine, 5-HT）即

12、5-羟色胺又名血清素，是一种吲哚胺类脑肠肽，广泛分布于消化道中。人体内的5-HT约95%分布于消化道。已有报道证明肠内5-HT是一种多功能信号分子 17。并参与调控胃肠运动、分泌反射并可调解内脏疼痛18。5-HT信号系统的异常会导致胃肠功能性疾病的发生。胆囊切除术后5-HT水平紊乱，消化道蠕动加快、肠道水及电解质分泌增加导致腹泻。43、CCK（cholecystokinin, CCK）即胆囊收缩素，由小肠粘膜型细胞分泌，经十二指肠释放。生理条件下，CCK的主要功能是收缩胆囊，引起胆囊平滑肌收缩和Oddi括约肌舒张，促进胆汁排放19。胆囊切除后，CCK失去了作用的靶器官，便在血液及胃肠道中囤积，

13、使激素水平发生紊乱，从而导致胃肠道功能障碍，进而导致了腹泻的发生。有研究发现静脉注射 CCK 后结肠运动呈推进性增强并诱发腹痛、腹泻20。也有报道CCK 并非局限于乙状结肠粘膜局部发挥作用，还可作为激素通过血液循环发挥效应, 导致腹痛、腹泻等症状。国内外多项研究发现21，肠易激综合征腹泻型患者CCK的血清浓度及胃肠道内浓度与正常人相比确有异常，有报道CCK呈低水平，也有报道CCK升高。CCK水平异常是胆囊切除术后腹泻的原因之一。5、小结 有研究机构发现，胆囊切除术对50%的患者术前的疾病无治疗效果22，患者行胆囊切除术后，原有的症状持续存在，并且术后出现新的症状23,24，如腹泻等，认为有必要

14、对胆囊切除术的指征重新思考。无症状的胆囊结石，对其胆囊功能进行评估，如果胆囊排空率45%，胆囊无恶性疾病时，原则上采用非手术治疗或观察；有症状的胆囊结石，临床医生及患者共同评估手术的治疗效果，严格掌握手术适应证。胆囊切除术后注意调整饮食结构，保持良好的饮食习惯；调理好个人情绪，预防菌群失调以减少腹泻，必要时用消胆胺、考来替泊等药物治疗25。参考文献1 HYPERLINK /pubmed/?term=Krums%20LM%5BAuthor%5D&cauthor=true&cauthor_uid=23653936 Krums LM, HYPERLINK /pubmed/?term=Parfenov

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