本文選題：尿流動(dòng)力學(xué) + 阿米洛利　； 參考：《昆明醫(yī)科大學(xué)》2014年碩士論文

【摘要】：目的： 探討大鼠膀胱組織中三型酸敏感離子通道(acid-sensing ion channels,ASIC3)表達(dá)的變化及與膀胱逼尿肌活動(dòng)的關(guān)系,明確三型酸敏感離子通道蛋白與尿路刺激癥的關(guān)系。為臨床尿路刺激征以及OAB的治療提供新的研究思路。 方法： 選取成年雌性大鼠,通過環(huán)磷酰胺(CYP)腹腔注射、大腸桿菌膀胱灌注方法構(gòu)建大鼠OAB模型及細(xì)菌性膀膀胱炎模型。根據(jù)造模方法的不同,分為1、CYP大組,2、細(xì)菌大組。每組再分為正常組、OAB組(CYP大組)或膀胱炎組(細(xì)菌大組)、干預(yù)組。即：A1：正常組、B1:OAB組、C1:OAB干預(yù)組(OAB+阿米洛利)；A2:正常組、B2:膀胱炎組、C2：膀胱炎干預(yù)組(膀胱炎+阿米洛利)。對(duì)六組大鼠膀胱灌注生理鹽水或阿米洛利生理鹽水溶液,進(jìn)行尿流動(dòng)力學(xué)檢測。同時(shí)取六組大鼠的膀胱組織,進(jìn)行病理學(xué)檢查。并通過免疫組織化學(xué)染色、RT-PCR和western-blot方法測量其ASIC3含量的差異。 結(jié)果： 尿流動(dòng)力學(xué)提示：正常組大鼠儲(chǔ)尿期及排尿期未見明顯不穩(wěn)定收縮；OAB組、膀胱炎組及兩干預(yù)組在儲(chǔ)尿期可見不穩(wěn)定收縮,與正常組相比：排尿間隔明顯縮短(P0.01),排尿次數(shù)明顯增加(P0.01)；OAB干預(yù)組與OAB組相比,不穩(wěn)定收縮次數(shù)較少,排尿次數(shù)減少、排尿間隔延長(P0.05)；膀胱炎干預(yù)組與膀胱炎組相比,不穩(wěn)定收縮次數(shù)較少,排尿次數(shù)減少、排尿間隔延長(P0.05) 病理學(xué)檢測提示OAB組、膀胱炎組、OAB干預(yù)組及膀胱炎干預(yù)組中大鼠膀胱粘膜破壞；免疫組化提示：大鼠膀胱組織含有ASIC3;且ASIC3主要存在于膀胱粘膜上,ASIC抑制劑可以抑制膀胱粘膜上ASIC3的表達(dá)；肌層中含有少量的ASIC3。ASIC3抑制劑對(duì)肌層ASIC3無明顯作用。 RT-PCR及western-blot提示：OAB組及膀胱炎組中膀胱上ASIC3表達(dá)明顯升高(P0.01),加入ASIC3抑制劑后,OAB干預(yù)組、膀胱炎干預(yù)組ASIC3表達(dá)有所降低(高于正常組,P0.05；低于OAB組或膀胱炎組,P0.05)。 結(jié)論： 1、大鼠膀胱組織內(nèi)有ASIC3的基因及蛋白表達(dá),且ASIC3的基因及蛋白表達(dá)主要存在于膀胱粘膜上； 2、OAB大鼠模型和膀胱炎大鼠膀胱組織上ASIC3的基因及蛋白表達(dá)較正常大鼠增高,其表達(dá)量受ASIC抑制劑的影響較為明顯。 3、膀胱內(nèi)ASIC3表達(dá)升高膀胱逼尿肌反射亢進(jìn)密切相關(guān)。 4、阿米洛利可能成為潛在的治療膀胱逼尿肌反射亢進(jìn)的藥物
[Abstract]:Objective: to investigate the expression of acid-sensing ion channel ASIC3 in rat bladder and its relationship with detrusor activity, and to clarify the relationship between acid sensitive ion channel protein and urinary tract irritation. Methods: OAB model and bacterial bladder cystitis model of adult female rats were established by intraperitoneal injection of cyclophosphamide (Cyp) and intravesical instillation of Escherichia coli. According to the different methods of modeling, it was divided into 1 CYP group (2) and bacteria group (2). Each group was divided into normal group (OAB group) or cystitis group (large bacterial group, intervention group). That is: normal group: B 1: OAB group C 1: OAB intervention group A 2: normal group B 2: cystitis group C 2: cystitis intervention group C 2: cystitis amilolol group. Six groups of rats were given intravesical instillation of normal saline or amiloride saline solution, and the urodynamics was measured. At the same time, the bladder tissues of six groups of rats were taken for pathological examination. The content of ASIC3 was measured by immunohistochemical staining RT-PCR and western-blot. Results: the urodynamics indicated that there was no obvious unstable contraction in normal rats during the period of urine storage and urination. In the cystitis group and the two intervention groups, the unstable contraction was observed in the period of urinary storage. Compared with the normal group, the interval of urination was significantly shorter than that in the control group, and the frequency of urination increased significantly in the OAB group compared with the OAB group, the frequency of unstable contraction was less, and the frequency of urination was less in the OAB group than in the OAB group. Compared with cystitis group, the number of unstable contraction was less and the number of micturition decreased in cystitis intervention group. The bladder mucosa was destroyed in the OAB group and the cystitis intervention group, and the expression of ASIC3 was inhibited by ASIC3 in the bladder tissue of the rats, and ASIC3 was mainly present in the bladder mucosa of the rats, and the expression of ASIC3 in the bladder mucosa was inhibited by ASIC3 inhibitor. ASIC3. ASIC3 inhibitor in myometrium had no obvious effect on ASIC3. RT-PCR and western-blot indicated that ASIC3 expression in bladder increased significantly in the two groups, and the expression of ASIC3 in the bladder was significantly increased after adding ASIC3 inhibitor, and the expression of ASIC3 was significantly increased in the control group after addition of ASIC3 inhibitor, and the expression of ASIC3 was significantly increased in the control group after addition of ASIC3 inhibitor. The expression of ASIC3 in cystitis intervention group was lower than that in normal group (P 0.05), and lower than that in OAB group or cystitis group (P 0.05). Conclusion: 1, ASIC3 gene and protein expression were found in bladder tissue of rats. The expression of ASIC3 gene and protein was mainly found in bladder mucosa, and the expression of ASIC3 gene and protein in bladder tissue of rats with OAB and cystitis was higher than that of normal rats. The expression of ASIC3 was significantly affected by ASIC inhibitor. 3The increase of ASIC3 expression in bladder was closely related to hyperreactivity of bladder detrusor reflex. 4. Amilolol may be a potential drug for the treatment of bladder detrusor hyperreflexia.
【學(xué)位授予單位】：昆明醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2014
【分類號(hào)】：R694.5

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