本文選題：遺尿癥 + 逼尿肌不穩(wěn)定��； 參考：《成都中醫(yī)藥大學(xué)》2014年博士論文

【摘要】：研究背景： 遺尿癥是兒童臨床常見疾病之一。遺尿患兒長期得不到診治,將會(huì)降低其生活質(zhì)量,影響兒童心理和人格的健康發(fā)展,其心理問題甚至?xí)z留終身。由此,探尋遺尿癥早期而有效的干預(yù),是一項(xiàng)具有深遠(yuǎn)社會(huì)意義的工作,也是一個(gè)重大而艱巨的課題。近年來,現(xiàn)代醫(yī)學(xué)對(duì)本病展開了多方位的研究,其具體發(fā)病機(jī)制雖不十分明確,但膀胱逼尿肌不穩(wěn)定無疑已成為目前國內(nèi)外研究本病的主要方向之一,逼尿肌不穩(wěn)定是臨床最常見的膀胱尿道功能障礙之一,而膀胱中ICCs樣細(xì)胞數(shù)量的增多可能是引起逼尿肌不穩(wěn)定產(chǎn)生的主要原因之一；一氧化氮(NO)作為抑制性非腎上腺能神經(jīng)非膽堿能神經(jīng)(NANC)神經(jīng)遞質(zhì),也參與了膀胱功能的調(diào)節(jié)。同時(shí),作為目前為止研究得最清楚的神經(jīng)營養(yǎng)因子,神經(jīng)生長因子(NGF)水平的變化可直接影響病理性膀胱神經(jīng)的分布。 中醫(yī)對(duì)本病的認(rèn)識(shí)有兩千多年的歷史,積累了豐富的臨床治療經(jīng)驗(yàn)。因此從中醫(yī)藥研究本病有可能成為在本病治療方法上的有益補(bǔ)充。我們?cè)谇捌诘呐R床觀察中發(fā)現(xiàn)越婢湯治療小兒遺尿癥療效肯定,故本研究以越婢湯為干預(yù)方劑,探討越婢湯對(duì)遺尿癥不穩(wěn)定膀胱模型的作用機(jī)制。 研究目的： 探討越婢湯對(duì)遺尿癥不穩(wěn)定膀胱模型的作用機(jī)制,從而對(duì)中醫(yī)“提壺揭蓋”“下病上取”,以及“肺為水之上源”等理論作出現(xiàn)代實(shí)驗(yàn)科學(xué)的嚴(yán)謹(jǐn)論證。 研究方法： 將108只wistar大鼠隨機(jī)分為膀胱出口梗阻手術(shù)組和假手術(shù)組,6周后行尿動(dòng)力檢查篩選出手術(shù)組膀胱逼尿肌不穩(wěn)定大鼠和假手術(shù)組膀胱逼尿肌穩(wěn)定大鼠進(jìn)行研究。將手術(shù)組膀胱逼尿肌不穩(wěn)定大鼠隨機(jī)分為越婢湯古方組、越婢湯高劑量組、越婢湯中劑量組、越婢湯低劑量組、縮泉丸對(duì)照組、模型對(duì)照組,加上假手術(shù)組共7組,每組10-13只大鼠。給藥14天后觀察越婢湯各劑量組對(duì)模型的影響。從膀胱濕重、膀胱膿腫和結(jié)石情況宏觀觀察藥物對(duì)模型的療效,用免疫組化和western blot方法測(cè)試膀胱ICCS細(xì)胞含量；用酶聯(lián)免疫法(ELISA).免疫組化測(cè)試血清和膀胱NOS蛋白含量；用ELISA、免疫組化測(cè)試血清、下丘腦和膀胱NGF蛋白含量；并做出數(shù)據(jù)處理分析,從多角度探討越婢湯對(duì)不穩(wěn)定膀胱的可能作用機(jī)制。 研究結(jié)果： 1.造模結(jié)果：手術(shù)6周后,經(jīng)尿動(dòng)力學(xué)檢測(cè)儀進(jìn)行充盈性膀胱測(cè)壓檢測(cè),假手術(shù)組大鼠膀胱逼尿肌不穩(wěn)定(DI)發(fā)生率為16.7%(2/12)；手術(shù)組96只,尿路感染、漏尿死亡15只,其中63只出現(xiàn)DI,發(fā)生率為77.8%(63/81)。 2.宏觀療效：模型對(duì)照組大鼠膀胱發(fā)生膀胱膿腫1只,膀胱結(jié)石2只；越婢湯低劑量組大鼠發(fā)生膀胱膿腫1只,膀胱結(jié)石1只；其余各組未發(fā)現(xiàn)明顯膀胱膿腫和膀胱結(jié)石。與假手術(shù)組相比,模型對(duì)照組大鼠膀胱濕重明顯增高,具有非常顯著的統(tǒng)計(jì)學(xué)意義(P0.01),與模型對(duì)照組相比,越婢湯組大鼠膀胱濕重明顯減輕,具有統(tǒng)計(jì)學(xué)意義(P0.05)。 3.藥物對(duì)膀胱ICCs細(xì)胞的影響：與假手術(shù)組比較,模型組膀胱逼尿肌ICCs細(xì)胞顯著增多(P0.05)；與模型組比較,越婢湯干預(yù)后膀胱逼尿肌ICCs細(xì)胞有顯著減少(P0.05)或表現(xiàn)出一定的量效關(guān)系。 4.藥物對(duì)NOS的影響： (1)膀胱組織免疫組化檢查： 與假手術(shù)組相比,模型對(duì)照組大鼠膀胱NOS含量明顯增多,具有非常顯著的統(tǒng)計(jì)學(xué)意義(P0.01)；與模型對(duì)照組相比,越婢湯干預(yù)后大鼠膀胱NOS含量明顯減少,具有顯著的統(tǒng)計(jì)學(xué)意義(P0.01),提示：越婢湯可以明顯下調(diào)大鼠膀胱NOS含量。 (2)血清ELISA檢測(cè)： 與假手術(shù)組相比,模型對(duì)照組大鼠血清NOS含量明顯增多,具有非常顯著的統(tǒng)計(jì)學(xué)意義(P0.01)；與模型對(duì)照組相比,越婢湯干預(yù)后大鼠血清NOS有下調(diào)趨勢(shì)。 5.藥物對(duì)神經(jīng)生長因子(NGF)的影響： (1)膀胱組織免疫組化檢查：與假手術(shù)組相比,模型對(duì)照組大鼠膀胱中NGF蛋白含量明顯降低,具有非常顯著的差異(P0.01)；與模型對(duì)照組相比,越婢湯干預(yù)后大鼠膀胱中NGF蛋白含量明顯升高,具有顯著的差異(P0.05),說明越婢湯具有上調(diào)DI大鼠膀胱組織NGF的作用。 (2)下丘腦免疫組化檢查：與假手術(shù)組相比,模型對(duì)照組大鼠下丘腦中NGF蛋白含量明顯降低,具有非常顯著的差異(P0.01)；與模型對(duì)照組相比,越婢湯干預(yù)后大鼠下丘腦中NGF蛋白含量明顯升高,具有非常顯著的差異(P0.05)；說明越婢湯具有上調(diào)DI大鼠下丘腦NGF的作用。 (3)血清ELISA檢測(cè)：與假手術(shù)組相比,模型對(duì)照組大鼠血清中NGF蛋白含量明顯降低,具有非常顯著差異(P0.01)；與模型對(duì)照組相比,越婢湯干預(yù)后大鼠血清中NGF蛋白含量明顯升高(P0.05),說明越婢湯具有上調(diào)DI大鼠血清NGF的作用。 研究結(jié)論： 1.越婢湯可以顯著改善逼尿肌不穩(wěn)定引起的膀胱功能障礙。 2.逼尿肌不穩(wěn)定膀胱中ICCs細(xì)胞數(shù)量升高；膀胱組織和血清NOS含量升高；血清、下丘腦和膀胱組織中NGF含量均降低。 3.越婢湯古方組和高劑量組可以明顯下調(diào)膀胱ICCs細(xì)胞數(shù)量,下調(diào)膀胱組織NOS含量,上調(diào)血清、下丘腦和膀胱組織中NGF含量,其對(duì)遺尿癥的治療機(jī)理可能與此有關(guān)。
[Abstract]:Research background:
Enuresis is one of the common clinical diseases in children. Children with enuresis can not be diagnosed and treated for a long time, which will reduce their quality of life, affect the healthy development of children's psychology and personality, and their psychological problems will remain for life. Therefore, to explore the early and effective intervention of enuresis is a work with far-reaching social significance and a great and hard work. In recent years, modern medicine has carried out a multidimensional study on this disease. Although its specific pathogenesis is not very clear, the detrusor instability of the bladder has undoubtedly become one of the main directions for studying this disease at home and abroad. Detrusor instability is one of the most common bladder urethral dysfunction, and ICCs like cells in the bladder. The increase in quantity may be one of the major causes of detrusor instability; nitric oxide (NO), as an inhibitory non adrenalenine non cholinergic neurotransmitter (NANC), is also involved in the regulation of bladder function. At the same time, as the most clearly known neurotrophic factor, the level of Neurogrowth factor (NGF) is at present. Changes can directly affect the distribution of pathological bladder nerves.
Chinese medicine has a history of more than two thousand years and has accumulated rich experience in clinical treatment. Therefore, the study of this disease from traditional Chinese medicine may be a useful supplement to the treatment of this disease. Effect of Yue Mau Decoction on unstable bladder model of enuresis.
The purpose of the study is:
The mechanism of Yue maidu Decoction on the unstable bladder model of enuresis is discussed, and the rigorous demonstration of modern experimental science is made on the theory of "lifting the lid of the pot" and "taking the disease on the bottom" and "the lung is the source of water" in traditional Chinese medicine.
Research methods:
108 Wistar rats were randomly divided into the operation group of bladder outlet obstruction and the sham operation group. After 6 weeks, the urinary bladder detrusor instability rats and the sham group were selected to study the bladder detrusor stable rats. The bladder detrusor instability rats were randomly divided into the Yue maidu Decoction group and the high dose of the Yue Maidan Decoction group. The dose group of Yue maidu decoction, the lower dose group of Yue maidu, the control group of the shinquan pill, the model control group, and the sham operation group, 7 groups, each group of 10-13 rats. After 14 days of administration, the effect of each dose group on the Yue Maidan Decoction on the model was observed. The effect of the drug on the model was observed from the wet weight of the bladder, bladder abscess and stone, by immunohistochemistry and Western blot prescription. The content of ICCS cells in bladder was tested by method of enzyme linked immunosorbent assay (ELISA). The content of serum and bladder NOS protein was measured by immunohistochemistry; the content of NGF protein in the hypothalamus and bladder was measured with ELISA, immunohistochemistry and the data processing analysis was made to discuss the possible mechanism of the action of Yue maidu soup to the unstable bladder.
The results of the study:
1. model results: after 6 weeks of operation, the bladder detrusor instability (DI) was 16.7% (2/12) in the sham operation group, 96 in the operation group, 15 in urinary tract infection and leakage of urine, of which 63 had DI, and the incidence was 77.8% (63/81).
2. macroscopical effect: the bladder abscess in the bladder of the model control group was 1, and the bladder stone was 2. The lower dose group of Yue maidu decoction had 1 bladder abscesses and 1 bladder stones. The other groups did not find obvious bladder abscess and bladder stone. Compared with the sham operation group, the wet weight of the bladder was significantly higher in the model control group, which was very significant. Statistical significance (P0.01), compared with the model control group, the weight of bladder wet weight of the rats in the Yue maiden group was significantly reduced, with statistical significance (P0.05).
The effect of 3. drugs on bladder ICCs cells: compared with the sham group, the ICCs cells of the bladder detrusor muscle in the model group increased significantly (P0.05). Compared with the model group, the ICCs cell of the bladder detrusor was significantly reduced (P0.05) or showed a certain dose effect relationship with the model group.
4. effects of drugs on NOS:
(1) immunohistochemical staining of bladder tissue:
Compared with the sham operation group, the NOS content of the bladder in the model control group increased significantly, and had significant statistical significance (P0.01). Compared with the model control group, the NOS content of the bladder in the rats after the Yue Maidan Decoction decreased significantly (P0.01). It was suggested that the Yue Maidan decoction could obviously reduce the content of NOS in the bladder of rats.
(2) serum ELISA detection:
Compared with the sham operation group, the serum NOS content of the rats in the model control group increased significantly and had significant statistical significance (P0.01). Compared with the model control group, the serum NOS of the rats of the Yue Maidan decoction was downregulated.
5. effects of drugs on nerve growth factor (NGF):
(1) immunohistochemical staining of bladder tissue: compared with the sham group, the NGF protein content in the bladder of the model control group was significantly lower than that in the model control group (P0.01). Compared with the model control group, the content of NGF protein in the bladder of the Yue maidu decoction was significantly higher than that in the model control group, with significant difference (P0.05), indicating that the Yue maidu soup was up to up DI. The effect of NGF on the bladder tissue of rats.
(2) immunohistochemical examination of hypothalamus: compared with the sham group, the NGF protein content in the hypothalamus of the model control group was significantly lower than that in the model control group (P0.01). Compared with the model control group, the NGF protein content in the hypothalamus of the Yue maidu decoction was significantly higher than that in the model control group, with a very significant difference (P0.05). It can increase the effect of NGF in the hypothalamus of DI rats.
(3) serum ELISA detection: compared with the sham group, the serum NGF protein content in the model control group was significantly lower than that in the model control group (P0.01). Compared with the model control group, the serum NGF protein content in the serum of the Yue Maidan decoction was significantly increased (P0.05), and that the Ming Yue maidservant soup was able to increase the role of NGF in the serum of DI rats.
The conclusions are as follows:
1. Yue maidu decoction can significantly improve bladder dysfunction caused by detrusor instability.
2. detrusor instability, ICCs cells in bladder increased, bladder tissue and serum NOS content increased, serum, hypothalamus and bladder tissue NGF content decreased.
The number of bladder ICCs cells and the content of NOS in bladder tissue were down regulated by the 3. Yue maidservant Decoction and the high dose group, and the content of NGF in the serum, hypothalamus and bladder tissue was up-regulated. The mechanism of the treatment of enuresis may be related to this.
【學(xué)位授予單位】：成都中醫(yī)藥大學(xué)
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2014
【分類號(hào)】：R272

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本文編號(hào)：1991759