1、膽囊切除術(shù)后腹瀉相關(guān)原因的研究進展馮其貞1 李建軍*（濟寧醫(yī)學院臨床學院，山東 濟寧 ，272067）摘要 膽囊結(jié)石在我國發(fā)病率較高，是臨床常見疾病。目前膽囊結(jié)石的主要治療手段仍然是膽囊切除術(shù)。隨著膽囊切除手術(shù)例數(shù)的增加，膽囊切除術(shù)后不良反應（又稱膽囊切除術(shù)后綜合征）也引起了廣泛的關(guān)注。膽囊切除術(shù)后綜合征以腹瀉最為常見，它不但直接影響患者的生活質(zhì)量，還導致結(jié)腸癌發(fā)病率的升高。所以正確認識膽囊切除術(shù)后腹瀉的原因十分必要。本文從不同角度對膽囊切除術(shù)后腹瀉的原因進行歸納、分析，以期為預防及治療膽囊切除術(shù)后腹瀉提供指導。關(guān)鍵詞 膽囊切除術(shù)；膽囊切除術(shù)后綜合征；腹瀉中途分類號 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膽囊結(jié)石在臨床病例中較為常見，發(fā)病率高，目前膽囊切除術(shù)仍是治療膽囊結(jié)石的首選治療手段，其術(shù)后的不良反應也隨著病例數(shù)的增加越來越受關(guān)注。據(jù)基金項目：山東省青少年教育科學研究課題（14BSH216）；山東省青少年教育科學研究課題評審辦公室作者單位：濟寧醫(yī)學院臨床學院，山東 濟寧 272067通訊作者：李建軍，Email：lixv16有關(guān)文獻報道，膽囊切除術(shù)后綜合征的發(fā)生率約為12%-47%1,2。臨床表現(xiàn)以疼痛和非

6、疼痛癥狀為主，分別約占25%和43%。在非疼痛癥狀中，以腹瀉癥狀最為常見3。膽囊切除術(shù)后腹瀉發(fā)生率各家報道不一，Sand報告為15%，且膽囊切除術(shù)后腹瀉發(fā)生率高、持續(xù)時間長、難以治療4。另有資料證明，膽囊切除術(shù)后腹瀉是近端結(jié)腸癌的危險因素之一5。所以，明確膽囊切除術(shù)后導致腹瀉的相關(guān)原因具有重要的意義。膽囊切除術(shù)后出現(xiàn)腹瀉的原因爭議很大，可能與膽囊功能、膽汁成分、患者個體狀態(tài)、神經(jīng)內(nèi)分泌等因素有關(guān)。1、膽囊功能的影響膽囊切除術(shù)后初期，膽管還沒有來得及代償，肝臟產(chǎn)生的膽汁直接排至腸道，而進食后只有少量膽汁酸鹽排入腸道，脂類的乳化、吸收不全在腸腔堆積致滲透性脂瀉。膽囊切除約3個月后，膽管代償，替代了

7、部分膽囊功能，膽汁的排出具有節(jié)律性，類脂的消化與吸收較前充分腹瀉減輕。孫誠誼等6認為，膽囊功能的喪失直接導致了慢性腹瀉，近端結(jié)腸癌、胰腺癌、肝細胞癌、食管腺癌發(fā)病率升高。鄒大中等研究膽囊排空率與患者術(shù)后腹瀉發(fā)生的相關(guān)性，認為以膽囊排空率45%為界限，術(shù)前測得膽囊排空率大于或等于45%的患者術(shù)后腹瀉發(fā)生率相對較高，與此相反，術(shù)前膽囊排空率小于45%的患者術(shù)后腹瀉的發(fā)生率相對較低，并存在明顯差異性7。術(shù)前膽囊排空率越高，所反映出的膽囊功能越好，切除膽囊后，其功能的突然缺失，使機體不能完全代償，故術(shù)后腹瀉率就相對較高。膽囊濃縮功能的喪失也是腹瀉發(fā)生的原因之一，肝臟每天分泌800-1200ml膽汁，失

8、去膽囊濃縮功能后，過多的水分進入腸道，引起腹瀉。2、膽汁成分的影響B(tài)arkun等報道8，由于膽汁酸鹽吸收不良所導致的腹瀉，占所有腹瀉的30%-70%。膽汁酸鹽吸收障礙，導致腹瀉這一現(xiàn)象，在1967年被首次報道9。Nolan等通過臨床對照試驗發(fā)現(xiàn)，膽囊切除術(shù)后患者以及膽汁酸吸收障礙患者纖維母細胞生長因子19（FGF19）較正常人群明顯減少。FGF19在膽汁酸鹽的合成過程中起到負反饋調(diào)節(jié)的作用，持續(xù)低水平的FGF19致使肝臟不斷合成膽汁酸，超出了回腸回吸收膽汁酸的最大限度，產(chǎn)生膽汁酸型腹瀉10。另有觀點認為，膽囊切除術(shù)后的患者，一方面，膽汁的排放節(jié)律失調(diào)，使膽鹽過多進入結(jié)腸，膽汁本身即有促使結(jié)腸蠕

9、動加快的作用，從而使過多的水分快速通過結(jié)腸而出現(xiàn)水樣便；再者，腸腔內(nèi)的厭氧菌作用于排入結(jié)腸的膽鹽，使之羥基化成雙羥膽酸，后者不僅促進腸蠕動，還能抑制結(jié)腸對水分的吸收，加劇腹瀉11。有學者還認為，通過糞便丟失大量膽鹽時也可引起腹瀉12。這一觀點也被術(shù)后腹瀉患者糞便中膽汁酸鹽成分明顯高于對照組這一事實所證明 13。3、患者的個體狀態(tài)Fisher等14認為膽囊切除術(shù)后腹瀉與患者年齡及體重指數(shù)有明確的相關(guān)性。高齡患者膽囊切除術(shù)后腹瀉的發(fā)生率遠遠低于中青年，分析其可能原因： 一是年輕人相對老年人進食油膩性食物的量及頻率較高。二是老年人由于機體各器官功能均有不同程度的衰退，膽囊功能在其衰退過程中，部分被膽

10、管代償，而中青年患者這種代償功能較差，機體對膽囊功能的依賴性大，膽囊切除后伴隨膽囊功能的喪失，進食含油性食物時，機體很難在短時間內(nèi)釋放足量膽鹽，食物中的脂肪消化及吸收障礙，引起脂肪性腹瀉。體重指數(shù)高的患者比體重指數(shù)低的患者發(fā)生腹瀉的概率較高。 Yueh等15認為術(shù)前腹瀉、胃腸功能紊亂、性格缺陷、藥物的影響、不潔飲食、高脂膳食等都可能是膽囊切除術(shù)后出現(xiàn)腹瀉的原因。術(shù)前無腹瀉的患者當中，小于45歲者，膽囊切除后出現(xiàn)腹瀉的明顯增多，且男性膽囊切除后較女性膽囊切除后出現(xiàn)腹瀉的可能性大。建議年齡小于等于45周歲的男性，在行膽囊切除術(shù)后1周內(nèi)進食低脂飲食，以避免腹瀉的發(fā)生。另有研究發(fā)現(xiàn)，切除膽囊會使患者腸

11、道內(nèi)的菌群失調(diào)，一方面表現(xiàn)為有益菌的減少，如雙歧桿菌、乳酸桿菌等；另一方面表現(xiàn)為有害機體的細菌增多，如大腸埃希菌、腸球菌等。從腸道菌群平衡的角度解釋了膽囊切除術(shù)后發(fā)生腹瀉的可能機制。4、神經(jīng)內(nèi)分泌因素目前已發(fā)現(xiàn)的腦腸肽約有40多種，多種與膽囊切除術(shù)后的腹瀉相關(guān)，主要有VIP、CCK、5-HT等。41、VIP（Vasoactive Intestinal Peptide, VIP）血管活性腸肽又名舒血管腸肽，在胃腸道中含量最高，能促進膽汁、小腸電解質(zhì)和水的分泌，誘發(fā)腸道動力增強16。有報道膽囊切除術(shù)后VIP水平升高可導致腹瀉 。42、5-HT（5-hydroxytryptamine, 5-HT）即

12、5-羥色胺又名血清素，是一種吲哚胺類腦腸肽，廣泛分布于消化道中。人體內(nèi)的5-HT約95%分布于消化道。已有報道證明腸內(nèi)5-HT是一種多功能信號分子 17。并參與調(diào)控胃腸運動、分泌反射并可調(diào)解內(nèi)臟疼痛18。5-HT信號系統(tǒng)的異常會導致胃腸功能性疾病的發(fā)生。膽囊切除術(shù)后5-HT水平紊亂，消化道蠕動加快、腸道水及電解質(zhì)分泌增加導致腹瀉。43、CCK（cholecystokinin, CCK）即膽囊收縮素，由小腸粘膜型細胞分泌，經(jīng)十二指腸釋放。生理條件下，CCK的主要功能是收縮膽囊，引起膽囊平滑肌收縮和Oddi括約肌舒張，促進膽汁排放19。膽囊切除后，CCK失去了作用的靶器官，便在血液及胃腸道中囤積，

13、使激素水平發(fā)生紊亂，從而導致胃腸道功能障礙，進而導致了腹瀉的發(fā)生。有研究發(fā)現(xiàn)靜脈注射 CCK 后結(jié)腸運動呈推進性增強并誘發(fā)腹痛、腹瀉20。也有報道CCK 并非局限于乙狀結(jié)腸粘膜局部發(fā)揮作用，還可作為激素通過血液循環(huán)發(fā)揮效應, 導致腹痛、腹瀉等癥狀。國內(nèi)外多項研究發(fā)現(xiàn)21，腸易激綜合征腹瀉型患者CCK的血清濃度及胃腸道內(nèi)濃度與正常人相比確有異常，有報道CCK呈低水平，也有報道CCK升高。CCK水平異常是膽囊切除術(shù)后腹瀉的原因之一。5、小結(jié) 有研究機構(gòu)發(fā)現(xiàn)，膽囊切除術(shù)對50%的患者術(shù)前的疾病無治療效果22，患者行膽囊切除術(shù)后，原有的癥狀持續(xù)存在，并且術(shù)后出現(xiàn)新的癥狀23,24，如腹瀉等，認為有必要

14、對膽囊切除術(shù)的指征重新思考。無癥狀的膽囊結(jié)石，對其膽囊功能進行評估，如果膽囊排空率45%，膽囊無惡性疾病時，原則上采用非手術(shù)治療或觀察；有癥狀的膽囊結(jié)石，臨床醫(yī)生及患者共同評估手術(shù)的治療效果，嚴格掌握手術(shù)適應證。膽囊切除術(shù)后注意調(diào)整飲食結(jié)構(gòu)，保持良好的飲食習慣；調(diào)理好個人情緒，預防菌群失調(diào)以減少腹瀉，必要時用消膽胺、考來替泊等藥物治療25。參考文獻1 HYPERLINK /pubmed/?term=Krums%20LM%5BAuthor%5D&cauthor=true&cauthor_uid=23653936 Krums LM, HYPERLINK /pubmed/?term=Parfenov

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