發(fā)布時(shí)間：2018-02-09 03:28

  本文關(guān)鍵詞： 神經(jīng)源性尿路障礙 大電鈣激活鉀通道 影像尿動(dòng)力學(xué) 輸尿管功能　出處：《鄭州大學(xué)》2014年碩士論文　論文類型：學(xué)位論文

【摘要】：目的 神經(jīng)源性尿路功能障礙(Neurogenic urinary tract dysfunction NUTD)是指任何與排尿有關(guān)中樞和神經(jīng)受到損傷，出現(xiàn)的尿路功能障礙。有效持久保護(hù)上尿路和提高生活質(zhì)量是NUTD基本治療原則；傳統(tǒng)研究表明，上尿路惡化很可能發(fā)生在排尿時(shí)尿道壓力高或膀胱內(nèi)的壓力升高。NUTD的治療的主要目標(biāo)是實(shí)現(xiàn)低尿液儲(chǔ)存壓力，以保護(hù)上尿路功能。盡管口服抗膽堿能藥物、逼尿肌注射A型肉毒毒素，并且結(jié)合清潔間歇導(dǎo)尿(CIC)，或進(jìn)行外科干預(yù)（如自體膀胱擴(kuò)大術(shù)或腸道膀胱擴(kuò)大術(shù)），可以有效的減低膀胱內(nèi)壓，提高膀胱容量和順應(yīng)性，但部分患者仍出現(xiàn)反流性上尿路損害。提示除下尿路繼發(fā)性尿動(dòng)力學(xué)高危因素外，NUTD上尿路損害發(fā)生還可能與神經(jīng)系統(tǒng)失去對(duì)輸尿管的功能支配后輸尿管發(fā)生自身功能障礙有關(guān)。本研究通過(guò)對(duì)骶髓損傷神經(jīng)源性逼尿肌無(wú)收縮兔模型建立后兩個(gè)月的輸尿管功能及鈣離子相關(guān)通道檢測(cè)，初步探討NUTD早期輸尿管功能變化、病理學(xué)改變以及大電鈣激活鉀通道(large-conductance Ca2+-activated K+channels,BKca)的表達(dá)情況，以了解NUTD上尿路功能變化及其機(jī)制，為預(yù)防反流性上尿路損害發(fā)生和阻斷其進(jìn)展提供理論依據(jù)。 方法 1.動(dòng)物模型的建立：將30只日本大耳白兔隨機(jī)均分為NUTD組、實(shí)驗(yàn)對(duì)照組和空白對(duì)照組。NUTD組：以復(fù)方鹽酸賽拉嗪注射液臀部肌肉注射（0.6ml/kg）麻醉后，俯臥固定，于背部沿L5-L7棘突行縱形切口，逐層分離皮暴露L6棘突，，在L6棘突兩側(cè)鈍性分離腰大肌，單關(guān)節(jié)咬骨鉗咬除L6棘突，暴露髓腔，眼科剪銳性橫斷脊髓，眼科鑷進(jìn)入髓腔鉗夾搗毀橫斷面下骶髓，填充無(wú)菌明膠海綿，逐層關(guān)閉切口，2周后行脊柱MRI和影像尿動(dòng)力學(xué)檢查證實(shí)存在明確神經(jīng)損害，膀胱表現(xiàn)為逼尿肌無(wú)收縮但無(wú)膀胱輸尿管反流；實(shí)驗(yàn)對(duì)照組：僅咬除棘突，未破壞脊髓，2周后行脊柱MRI和尿動(dòng)力學(xué)檢查證實(shí)不存在明確神經(jīng)損害，無(wú)明顯膀胱尿道功能障礙；空白對(duì)照組：未進(jìn)行任何手術(shù)處理。 2.建模后2月行影像尿動(dòng)力學(xué)測(cè)定、輸尿管功能評(píng)估、形態(tài)學(xué)觀察及輸尿管標(biāo)本制作。 3.應(yīng)用免疫組織化學(xué)法、熒光定量PCR和Western blot檢測(cè)其輸尿管平滑肌細(xì)胞（USMC）BKca mRNA和蛋白表達(dá)情況。 結(jié)果 1.發(fā)現(xiàn)動(dòng)物模型建立后2月NUTD組表現(xiàn)為逼尿肌無(wú)收縮，無(wú)膀胱輸尿管反流發(fā)生； 2.在1ml/kg/min恒定速度靜脈滴注生理鹽水條件下，NUTD組30min內(nèi)產(chǎn)生的尿量為（18.5±3.7）ml、實(shí)驗(yàn)對(duì)照組為（19.5±2.4）ml、空白對(duì)照組為（17.8±3.2）ml，三組間的差異無(wú)統(tǒng)計(jì)學(xué)意義；但左側(cè)輸尿管蠕動(dòng)次數(shù)NUTD組（39.0±3.0）顯著低于實(shí)驗(yàn)對(duì)照組（44.0±5.0）和空白對(duì)照組（46.0±4.0），差異有統(tǒng)計(jì)學(xué)意義(P 0.05)； 3.光鏡下NUTD組輸尿管上皮細(xì)胞、固有層和肌層無(wú)明顯變化，外膜有不同程度的充血和炎細(xì)胞浸潤(rùn)； 4. NUTD組USMC中BKcaα mRNA（2.89±0.67）和BKcaβ mRNA（4.59±1.22）表達(dá)相對(duì)于空白對(duì)照組mRNA（BKcaα：1.02±0.21；BKcaβ：1.03±0.28）顯著上調(diào)，差異有統(tǒng)計(jì)學(xué)意義（P＜0.001）；NUTD組BKcaα（1.35±0.32）和BKcaβ（1.47±0.10）蛋白表達(dá)相對(duì)于空白對(duì)照組（BKcaα：0.89±010；BKcaβ：1.03±0.13）顯著也上調(diào)，差異有統(tǒng)計(jì)學(xué)意義（P＜0.001）。 結(jié)論 1.神經(jīng)源性尿路障礙(NUTD)存在原發(fā)性輸尿管功能障礙； 2.原發(fā)性輸尿管功能障礙在神經(jīng)原性尿路功能障礙未發(fā)生膀胱輸尿管反流和病理改變時(shí)已經(jīng)發(fā)生； 3.輸尿管平滑肌細(xì)胞中BKca表達(dá)水平升高，可能是其出現(xiàn)輸尿管原發(fā)性功能障礙的原因之一。
[Abstract]:Purpose Neurogenic urinary tract dysfunction ( Neurogenic urinary tract dysfunction ) refers to any urinary tract dysfunction related to urinary tract dysfunction and urinary tract dysfunction . The main objective of this study is to reduce bladder internal pressure and improve bladder capacity and compliance . method 1 . Establishment of animal model : 30 Japanese white rabbits were randomly divided into two groups : Group D group , experimental control group and blank control group . 2 . Urodynamic measurement , ureter function evaluation , morphological observation and ureter specimen preparation were performed in February after modeling . 3 . Using immunohistochemical method , fluorescence quantitative PCR and Western blot to detect the mRNA and protein expression of the ureteral smooth muscle cells ( USMC ) . Results 1 . Two months after the establishment of the animal model , the group D showed no contraction and no vesicoureteral reflux . 2 . Under the condition of 1 ml / kg / min constant velocity intravenous drip , the urine volume was ( 18.5 鹵 3.7 ) ml , the experimental control group was ( 19.5 鹵 2.4 ) ml , the blank control group was ( 17.8 鹵 3.2 ) ml , the difference between the three groups was not statistically significant , but the left ureter wriggling frequency was significantly lower than that in the experimental control group ( 44.0 鹵 5.0 ) and the blank control group ( 46.0 鹵 4.0 ) , the difference was statistically significant ( P 0.05 ) ; 3 . There was no obvious change of ureter epithelial cells , lamina propria and muscular layer in the group D group under light microscope , and the outer membrane had different degrees of congestion and inflammatory cell infiltration . 4 . The expression of BK ca 偽 mRNA ( 2.89 鹵 0.67 ) and BK ca 尾 mRNA ( 4.59 鹵 1.22 ) in group D group was significantly up - regulated with respect to blank control group mRNA ( BK ca . 偽 : 1.02 鹵 0.21 ; BK ca . 尾 : 1.03 鹵 0.28 ) . The difference was statistically significant ( P < 0.001 ) . NUTD緇

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