張 倩(綜述)，陳繼紅(審校)

(武漢大學(xué)人民醫(yī)院消化內(nèi)科，武漢 430060)

近段結(jié)腸吸收內(nèi)容物的水分、電解質(zhì)和營養(yǎng)物質(zhì)[1]，遠(yuǎn)段結(jié)腸則負(fù)責(zé)糞便的存貯和排空。神經(jīng)系統(tǒng)、Cajal間質(zhì)細(xì)胞(interstitial cells of Cajal,ICC)和平滑肌細(xì)胞協(xié)同調(diào)控著結(jié)腸的運(yùn)動(dòng)模式。在體胃腸道的運(yùn)動(dòng)由中樞神經(jīng)、自主神經(jīng)和腸神經(jīng)共同支配[2]。去除外在神經(jīng)后，腸神經(jīng)系統(tǒng)(肌間神經(jīng)叢和黏膜下神經(jīng)叢)可獨(dú)立發(fā)揮作用。ICC與腸神經(jīng)系統(tǒng)密切相關(guān)，根據(jù)分布部位和功能分為漿膜層ICC[3]、肌間神經(jīng)叢相關(guān)ICC(ICC associated with the myenteric plexus，ICC-MP)[4]、肌束纖維隔內(nèi)ICC[3]、肌層內(nèi)ICC[5]和黏膜下神經(jīng)叢相關(guān)ICC(ICC associated with the submuscular plexus，ICC-SMP)[6]。離體動(dòng)物結(jié)腸研究中，常用動(dòng)物為大鼠、小鼠，可分為傳播性推進(jìn)性運(yùn)動(dòng)和傳播性非推進(jìn)性運(yùn)動(dòng)，前者節(jié)律性推進(jìn)性運(yùn)動(dòng)復(fù)合波(rhythmic propulsive motor complexes，RPMCs)多見，后者微小波多見。

1 推進(jìn)性運(yùn)動(dòng)

RPMCs[7]也被稱為結(jié)腸移行運(yùn)動(dòng)復(fù)合波[8]、巨大收縮[9]、袋狀收縮[9]或集團(tuán)蠕動(dòng)[9]。20世紀(jì)中期，人們在小鼠和貓的離體全結(jié)腸中首次發(fā)現(xiàn)RPMCs[10-11]，隨后其他研究小組也陸續(xù)觀察到[12]。1995年,Taylor稱之為結(jié)腸移行運(yùn)動(dòng)復(fù)合波[13]，命名類似小腸移行運(yùn)動(dòng)復(fù)合波。小腸移行運(yùn)動(dòng)復(fù)合波空腹時(shí)周期性出現(xiàn)，膽堿能腸神經(jīng)可增強(qiáng)移行運(yùn)動(dòng)復(fù)合波，而氮能腸神經(jīng)抑制其活動(dòng)[14-15]。當(dāng)時(shí)，研究者認(rèn)為RPMCs與小腸移行運(yùn)動(dòng)復(fù)合波一樣由腸神經(jīng)系統(tǒng)支配。但不同的是，RPMCs可自發(fā)產(chǎn)生，也可經(jīng)生理性刺激誘發(fā)[16]。隨后，一部分學(xué)者觀察到RPMCs可被河豚毒素阻斷，因此認(rèn)為RPMCs是一種節(jié)律性的、產(chǎn)生和傳播由腸神經(jīng)控制的神經(jīng)源性運(yùn)動(dòng)；而另一部分學(xué)者發(fā)現(xiàn)RPMCs對河豚毒素并不敏感，是一種肌源性運(yùn)動(dòng)。還有部分研究者發(fā)現(xiàn)在體RPMCs同時(shí)具有神經(jīng)源性和肌源性特征，但離體RPMCs僅有神經(jīng)源性特征[17]。對此，Huizinga等[7]認(rèn)為RPMCs起自ICC，腸神經(jīng)系統(tǒng)則為ICC提供主要刺激。神經(jīng)傳導(dǎo)阻滯劑(河豚毒素、利多卡因)抑制近段結(jié)腸RPMCs[18]，中段結(jié)腸RPMCs被阻斷但可被氯貝膽堿再次誘發(fā)，證實(shí)生理情況下神經(jīng)系統(tǒng)參與RPMCs的產(chǎn)生。但移除黏膜和黏膜下神經(jīng)叢，自發(fā)性和外源性刺激(神經(jīng)電刺激、結(jié)腸擴(kuò)張)誘發(fā)的RPMCs仍可見[12,19-20]，說明RPMCs的產(chǎn)生和傳播并非必需神經(jīng)遞質(zhì)介導(dǎo)。肌條研究得到類似結(jié)果[12,21]。

ICC-MP完整時(shí)才能觀察到RPMCs[17]。ICC-MP經(jīng)鈣離子觸發(fā)激活后，產(chǎn)生正向傳播的節(jié)律性一過性除極，其頻率和振幅取決于刺激源強(qiáng)度。鈣成像研究表明，在RPMCs間期，抑制性運(yùn)動(dòng)神經(jīng)元持續(xù)釋放神經(jīng)遞質(zhì)抑制ICC-MP，阻斷抑制性神經(jīng)后，ICC間出現(xiàn)持續(xù)性Ca2+電流。興奮性運(yùn)動(dòng)神經(jīng)元也可觸發(fā)ICC-MP的Ca2+電流[22]。ICC-MP和平滑肌細(xì)胞Ca2+電流增強(qiáng)，經(jīng)興奮性神經(jīng)激活環(huán)形肌和縱行肌，參與RPMCs的產(chǎn)生和傳播。研究發(fā)現(xiàn)阿托品抑制ICC-MP，神經(jīng)激肽1拮抗劑隨之阻斷，反之亦然。表明膽堿能神經(jīng)和速激肽神經(jīng)參與ICC-MP的激活[22]?？偠灾?，在各種內(nèi)、外刺激源作用下，興奮性運(yùn)動(dòng)神經(jīng)釋放乙酰膽堿和速激肽、抑制性運(yùn)動(dòng)神經(jīng)活動(dòng)減退，共同激活I(lǐng)CC網(wǎng)絡(luò)產(chǎn)生RPMCs。

2 傳播性非推進(jìn)性運(yùn)動(dòng)

目前研究最多的非推進(jìn)性運(yùn)動(dòng)是微小波。微小波是由ICC-SMP介導(dǎo)的高頻率、低振幅收縮，通常出現(xiàn)在結(jié)腸的頭段和中段[7-8,23]。微小波的速度、傳播方向和起始點(diǎn)千變?nèi)f化。電生理研究表明，微小波產(chǎn)生的基礎(chǔ)是ICC-SMP起源的慢波。由于慢波可以在任一時(shí)刻產(chǎn)生于ICC-SMP網(wǎng)絡(luò)上的任一點(diǎn)，且可以任一速度雙向傳播，引起平滑肌細(xì)胞節(jié)律性除極產(chǎn)生微小波[23-24]，因此微小波之間具有較大的差異性。但微小波起始時(shí)多為逆向傳播，方向常變，不能驅(qū)動(dòng)結(jié)腸推進(jìn)性運(yùn)動(dòng)[8]。其傳播距離短，僅推動(dòng)與黏膜表面接觸的內(nèi)容物，促進(jìn)水分吸收。全結(jié)腸研究和肌條研究均顯示微小波具有河豚毒素抵抗性，對其他神經(jīng)源性藥物(利多卡因)和肌源性藥物(氯貝膽堿)也無反應(yīng)[7,23]，提示微小波僅具有肌源性性質(zhì)。微小波與RPMCs常同時(shí)出現(xiàn)，但兩者的傳播方向不一定相同。ICC-SMP和ICC-MP是獨(dú)立的兩個(gè)網(wǎng)絡(luò)，彼此之間沒有聯(lián)系，慢波和與節(jié)律性一過性除極相互獨(dú)立，可同時(shí)反向傳播，因此微小波和RPMCs也可同時(shí)反向傳播[23]。

3 兔離體結(jié)腸運(yùn)動(dòng)模式研究

由于解剖差異較大，兔與大鼠、小鼠的結(jié)腸運(yùn)動(dòng)模式略有不同。兔結(jié)腸分四部分[25]，前三部分構(gòu)成近段結(jié)腸，第四部分為遠(yuǎn)段結(jié)腸：第一部分的三條結(jié)腸帶間形成結(jié)腸袋；第二部分僅有一條結(jié)腸帶和一側(cè)結(jié)腸袋；第三部分為腸鈕(fusus coli)，縱行肌環(huán)繞其外，與遠(yuǎn)段結(jié)腸連接于結(jié)腸曲。

Roger用高分辨率時(shí)空圖觀察到第一部分離體兔結(jié)腸存在四種運(yùn)動(dòng)模式[9]，①集團(tuán)蠕動(dòng)：快速傳播的外層環(huán)形肌收縮，伴有結(jié)腸帶縱行肌不規(guī)則收縮，收縮前有預(yù)舒張，對六甲胺敏感，正向集團(tuán)蠕動(dòng)傳播距離較逆向集團(tuán)運(yùn)動(dòng)長，回腸內(nèi)容物推入時(shí)差別更顯著；②袋裝傳播：緩慢正向環(huán)行收縮，對六甲胺敏感；③微小波：逆向環(huán)形收縮，傳播速度差異大，對六甲胺抵抗；④快相收縮：快速正向傳播的低幅度收縮，對六甲胺抵抗。快相收縮與結(jié)腸帶縱行肌收縮同時(shí)增加集團(tuán)蠕動(dòng)前的收縮幅度。

Dinning等[8]觀察到神經(jīng)源性的RPMCs、正向和逆向蠕動(dòng)以及肌源性的微小波。結(jié)腸腔內(nèi)環(huán)境的改變(內(nèi)容物體積增加、黏度增高等)誘發(fā)第一、第二部分交界處神經(jīng)源性運(yùn)動(dòng)——RPMCs[9]。六甲胺可阻斷RPMCs，說明煙堿能神經(jīng)通過興奮性腸神經(jīng)參與RPMCs的發(fā)生[26]。RPMCs恒速通過單結(jié)腸帶到達(dá)結(jié)腸曲[8,25]，可能參與糞便塑型[25]。逆向蠕動(dòng)多在正向蠕動(dòng)間期出現(xiàn)，傳播速度較小，20世紀(jì)初即有報(bào)道[27]。液體灌注遠(yuǎn)段結(jié)腸誘發(fā)逆向蠕動(dòng)，腸腔閉合，腔內(nèi)壓迅速升高。逆向蠕動(dòng)對河豚毒素敏感，但對六甲胺抵抗，說明非煙堿能腸神經(jīng)介導(dǎo)其發(fā)生、發(fā)展[28]。人為阻止內(nèi)容物排出，結(jié)腸出現(xiàn)不規(guī)律蠕動(dòng)，節(jié)律性蠕動(dòng)的產(chǎn)生易受干擾[8]。

兔微小波也起自慢波[29-30]，可雙向傳播，不被河豚毒素阻斷。微小波在結(jié)腸曲傳播較遠(yuǎn)段結(jié)腸快[8]，其速度反映了ICC網(wǎng)絡(luò)的密度，類似大鼠小腸[31]。Ehrlein把在體兔結(jié)腸的逆向微小波稱為滾動(dòng)性袋狀活動(dòng)[25]。河豚毒素作用下兔結(jié)腸明顯舒張，出現(xiàn)了低頻和高頻微小波，后者傳播速度遠(yuǎn)大于前者[8-9]。兩者分別來自肌間神經(jīng)叢和黏膜下層，高頻微小波也可能不經(jīng)慢波介導(dǎo)[32]。微小波起始點(diǎn)多變，說明起搏細(xì)胞的頻率并不恒定，但肛端頻率比近端高，因此微小波常逆向傳播。

4 結(jié) 語

目前，離體動(dòng)物結(jié)腸運(yùn)動(dòng)研究中觀察到的推進(jìn)性運(yùn)動(dòng)多為ICC-MP起源的節(jié)律性推進(jìn)性運(yùn)動(dòng)復(fù)合波，非推進(jìn)性運(yùn)動(dòng)則為ICC-SMP起源的微小波。神經(jīng)源性藥物對RPMCs和微小波的作用表明，離體結(jié)腸的運(yùn)動(dòng)功能與腸神經(jīng)關(guān)系并不明顯，鈣成像等研究進(jìn)一步證實(shí)了ICC網(wǎng)絡(luò)在結(jié)腸運(yùn)動(dòng)中起到的主導(dǎo)作用。盡管存在解剖、方法學(xué)和命名的差異，但人和動(dòng)物擁有相似的結(jié)腸運(yùn)動(dòng)模式，進(jìn)一步探索各種運(yùn)動(dòng)模式的特征和功能，將對疾病的防治獲得更深入的了解。

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