本文選題：阻塞性黃疸　切入點(diǎn)：運(yùn)動(dòng)功能　出處：《第二軍醫(yī)大學(xué)》2014年碩士論文

【摘要】：阻塞性黃疸，就是由物理、化學(xué)、免疫、生物等多種因素引起的膽汁排泄障礙，臨床多見(jiàn)于由肝內(nèi)外膽管梗阻造成的膽汁淤積，并經(jīng)常繼發(fā)肝臟功能的損害。 除了肝膽疾患外，阻塞性黃疸患者還常常伴有瘙癢和疲勞癥狀，嚴(yán)重影響了患者的生活質(zhì)量。特別是患者常常抱怨的“疲勞”，由于不是特異癥狀，因而常常被醫(yī)生忽視。近年，膽汁淤積患者疲勞研究逐漸得到重視，許多調(diào)查問(wèn)卷被用于評(píng)估量化疲勞狀態(tài)。由于疲勞是主觀癥狀，言語(yǔ)表述的問(wèn)卷評(píng)分難以客觀量化，而操作類量表則可較客觀反映疲勞程度。因此，在臨床研究中，選擇性別、年齡、受教育年限匹配的阻塞性黃疸病人和慢性膽囊炎非黃疸病人各20例，對(duì)其進(jìn)行紙筆試驗(yàn)測(cè)試，包括數(shù)字連接試驗(yàn)A型，線追蹤試驗(yàn)、系列打點(diǎn)試驗(yàn)和數(shù)字符號(hào)試驗(yàn)，它們可以反映黃疸與非黃疸病人間精神運(yùn)動(dòng)功能尤其是精細(xì)運(yùn)動(dòng)功能狀態(tài)的改變，量化評(píng)價(jià)運(yùn)動(dòng)疲勞的程度。 許多研究提示，膽汁淤積病人的疲勞可能與神經(jīng)遞質(zhì)及其受體的改變有關(guān)。已觀察到膽汁淤積的病人和動(dòng)物內(nèi)生阿片能神經(jīng)傳遞增強(qiáng)，而且有證據(jù)表明5-羥色胺（5-HT）能神經(jīng)傳遞參與了膽汁淤積狀態(tài)下運(yùn)動(dòng)疲勞的產(chǎn)生，那么中樞其他神經(jīng)遞質(zhì)系統(tǒng)是否也參與調(diào)節(jié)呢？影響神經(jīng)遞質(zhì)的突觸傳遞也是目前認(rèn)為的全身麻醉藥的作用機(jī)制之一，臨床常用的吸入麻醉藥七氟烷是否對(duì)此類病人的運(yùn)動(dòng)功能有不利影響？ 為回答這些問(wèn)題，本研究建立了膽總管結(jié)扎離斷SD大鼠模型（BDL模型），模擬膽汁淤積狀態(tài)。術(shù)后3周分別進(jìn)行曠場(chǎng)和轉(zhuǎn)棒測(cè)試，測(cè)量模型大鼠水平運(yùn)動(dòng)距離（反映自發(fā)活動(dòng)狀態(tài)）和轉(zhuǎn)棒滑落潛伏期（反映協(xié)調(diào)運(yùn)動(dòng)能力）。針對(duì)BDL大鼠普遍的運(yùn)動(dòng)抑制狀態(tài)，研究假定GABA能遞質(zhì)系統(tǒng)參與作用，分別給予干預(yù)組和對(duì)照組GABA-苯二氮卓受體復(fù)合體拮抗劑氟馬西尼和生理鹽水單次腹腔注射，觀察對(duì)比干預(yù)后上述動(dòng)物行為學(xué)指標(biāo)予以驗(yàn)證。七氟烷吸入麻醉則觀察干預(yù)前2天，干預(yù)后1天、4天、7天大鼠轉(zhuǎn)棒滑落潛伏期的變化。 進(jìn)一步通過(guò)在體電生理記錄BDL大鼠運(yùn)動(dòng)相關(guān)的腹內(nèi)側(cè)前額葉（mPFC）錐體神經(jīng)元放電的變化，探討B(tài)DL大鼠運(yùn)功功能損害的神經(jīng)機(jī)制。BDL大鼠術(shù)后3周麻醉后開(kāi)顱，玻璃微電極記錄錐體神經(jīng)元放電。腹腔給予氟馬西尼和乳化七氟烷注射，觀察神經(jīng)元的放電頻率、放電間隔、眾數(shù)等變化。 主要研究結(jié)果如下： 1.臨床研究：在4項(xiàng)紙筆測(cè)試中，阻塞性黃疸組病人成績(jī)均顯著低于對(duì)照組（P＜0.05），提示存在精神運(yùn)動(dòng)障礙，有精細(xì)運(yùn)動(dòng)功能減退。 2.動(dòng)物行為學(xué)實(shí)驗(yàn)研究：①與假手術(shù)組對(duì)照，BDL模型組水平運(yùn)動(dòng)距離和滑落潛伏期均顯著減少（P＜0.01），提示自發(fā)活動(dòng)和協(xié)調(diào)運(yùn)動(dòng)功能減退，模擬了臨床阻塞性黃疸伴隨的運(yùn)動(dòng)疲勞。②與對(duì)照組比較，在腹腔注射1mg/kg氟馬西尼后10分鐘至20分鐘期間，曠場(chǎng)活動(dòng)距離增加（P＜0.05）；在腹腔注射1mg/kg氟馬西尼后30分鐘內(nèi)，平均滑落潛伏期明顯延長(zhǎng)（P＜0.01），表明氟馬西尼改善了減退的運(yùn)動(dòng)功能。③與對(duì)照組比較，，吸入七氟烷前2天，吸入后1天、4天、7天，BDL大鼠轉(zhuǎn)棒滑落潛伏期無(wú)明顯差異（P＞0.05）。 3.電生理實(shí)驗(yàn)研究：①與假手術(shù)組比較，BDL模型組腹內(nèi)側(cè)前額葉皮層錐體神經(jīng)元放電頻率顯著下降，平均放電間隔顯著增加，放電眾數(shù)無(wú)明顯變化。每針扎到活動(dòng)神經(jīng)元數(shù)顯著減少。②BDL模型組腹腔注射氟馬西尼1mg/kg后5min，內(nèi)側(cè)前額葉皮層放電頻率顯著增加，平均放電間隔顯著減少，放電眾數(shù)無(wú)明顯變化。提示氟馬西尼可改善BDL大鼠內(nèi)側(cè)前額葉皮層的錐體神經(jīng)元電活動(dòng)水平。③BDL模型組腹腔注射乳化七氟烷后，放電頻率顯著增加，平均放電間隔顯著減少。 綜上所述可以得出如下結(jié)論： 1.阻塞性黃疸病人存在運(yùn)動(dòng)功能減退的表現(xiàn)，紙筆試驗(yàn)是臨床簡(jiǎn)便客觀的評(píng)價(jià)工具。 2. BDL大鼠模型模擬了臨床膽汁淤積造成的運(yùn)動(dòng)功能減退。 3.給予氟馬西尼能夠緩解膽汁淤積大鼠運(yùn)動(dòng)功能障礙，提示中樞GABA能神經(jīng)傳遞可能是重要機(jī)制。 4.七氟烷麻醉不加劇阻塞性黃疸大鼠運(yùn)動(dòng)功能減退。 5. mPFC錐體神經(jīng)元活動(dòng)性降低很可能是膽汁淤積致運(yùn)動(dòng)功能減退的原因之一。
[Abstract]:Obstructive jaundice is a biliary excretion disorder caused by a number of factors , such as physical , chemical , immunological , biological , etc . , and is frequently seen in the cholestatic caused by the obstruction of intrahepatic and external bile duct , and often secondary to hepatic impairment .

In addition to liver and gallbladder diseases , patients with obstructive jaundice often have itching and fatigue symptoms , which seriously affect the quality of life of patients . In recent years , the fatigue of patients with obstructive jaundice has been seriously neglected . In recent years , 20 patients with obstructive jaundice and non - jaundice patients with chronic cholecystitis have been neglected .

Many studies suggest that the fatigue of patients with cholestatic may be associated with changes in neurotransmitters and their receptors . It has been observed that the neurotransmission of endogenous opioid receptors in bile - stasis patients is enhanced , and there is evidence that serotonin ( 5 - HT ) is involved in the regulation of motor fatigue in the state of cholestatic . The synaptic transmission that affects neurotransmitters is also one of the mechanisms currently considered systemic anesthetics , and does the clinical use of inhaled anesthetics have an adverse effect on the exercise function of such patients ?

In order to answer these questions , the model ( BDL model ) of bile duct ligation and SD rat model ( BDL model ) was established to simulate the status of bile stasis .

In this paper , the nerve mechanism of the damage of the BDL rats was investigated by the changes of the discharge of the pyramidal neurons of the ventral medial frontal lobe ( mPFC ) related to the movement of the BDL rats .

The main results are as follows :

1 . Clinical study : In four paper - pen tests , the scores of patients with obstructive jaundice group were significantly lower than those in the control group ( P < 0.05 ) .

2 . Experimental study on animal behavior : 鈶

本文編號(hào)：1723194