本文選題：勃起功能障礙 + 海綿體神經(jīng)損傷��； 參考：《南方醫(yī)科大學(xué)》2017年碩士論文

【摘要】：背景和目的前列腺癌根治術(shù)(radicalprostatectomy,RP)是局限性前列腺癌的一線治療方法,但術(shù)后引起ED(RP-ED)的發(fā)病率高達(dá)30%-87%。同時(shí),RP-ED的病理機(jī)制尚不清楚,且對(duì)5型磷酸二酯酶抑制劑(phosphodiesterase 5 inhibitor,PDE5i)治療效果欠佳。伴隨結(jié)構(gòu)功能的不同,平滑肌細(xì)胞由收縮型轉(zhuǎn)化為增殖型的過(guò)程稱為表型轉(zhuǎn)化。我們前期研究證實(shí)糖尿病大鼠陰莖海綿體平滑肌細(xì)胞存在表型轉(zhuǎn)化,并且與糖尿病性大鼠的ED密切相關(guān)。Myocardin是平滑肌細(xì)胞表型調(diào)控過(guò)程中重要的調(diào)控因子,本課題組已證實(shí),Myocardin基因治療可改善糖尿病性大鼠陰莖勃起功能。本研究旨在建立雙側(cè)海綿體神經(jīng)損傷(bilateral cavernous nerve injury,BCNI)大鼠,明確BCNI大鼠陰莖海綿體平滑肌細(xì)胞是否發(fā)生表型轉(zhuǎn)化,初步探討B(tài)CNI大鼠ED的病理機(jī)制,并試圖通過(guò)Myocardin基因改善BCNI大鼠的勃起功能。方法1.雙側(cè)海綿體神經(jīng)損傷大鼠陰莖海綿體平滑肌細(xì)胞表型特征建立雙側(cè)海綿體神經(jīng)損傷大鼠及假手術(shù)組共36只,分別于3、5、7天對(duì)BCNI和NC組行勃起功能檢測(cè),計(jì)算出最大陰莖海綿體刺激壓/平均動(dòng)脈壓比率(intraeavemous pressure/mean arterial pressure,CP/MAP),并取陰莖中段組織行 western blot 檢測(cè) a-sma、calponin、Myocardin、OPN 蛋白的表達(dá)。另外行HE染色和Masson染色觀察大鼠陰莖組織組織形態(tài)學(xué)變化。2.Myocardin基因過(guò)表達(dá)對(duì)雙側(cè)海綿體損傷大鼠勃起功能及陰莖海綿體平滑肌細(xì)胞表型轉(zhuǎn)化的影響30只SD大鼠分為 3 組,即 BCNI+Ad-Myocardin 組、BCNI+Ad-vector 組及NC+PBS組,構(gòu)建Myocardin基因腺病毒,將純化的Myocardin腺病毒導(dǎo)入BCNI大鼠陰莖海綿體內(nèi),注射21天后檢測(cè)各組大鼠陰莖海綿體內(nèi)壓及頸動(dòng)脈壓,并取陰莖中段組織行 western blot 檢測(cè) a-sma、calponin、Myocardin、OPN 蛋白的表達(dá)。另外行HE染色、Masson染色和免疫組化和檢測(cè)大鼠陰莖組織形態(tài)學(xué)變化以及平滑肌含量結(jié)果第一章:造模3天、5天、7天后采用測(cè)定陰莖海綿體內(nèi)壓及頸動(dòng)脈壓的方法評(píng)價(jià)大鼠勃起功能,在ICP及MAP測(cè)定中結(jié)果顯示,BCNI大鼠ICP及AICP/MAP較NC組大鼠明顯下降,達(dá)到統(tǒng)計(jì)學(xué)差異(P0.05);western blot檢測(cè)發(fā)現(xiàn)第5天的BCNI大鼠陰莖海綿體組織中a-sma、Myocardin、calponin表達(dá)較NC大鼠顯著下調(diào),OPN的表達(dá)較NC組顯著上調(diào);在HE染色及Masson染色中BCNI大鼠及NC大鼠的平滑肌數(shù)量及形態(tài)無(wú)顯著差異。第二章:各組大鼠注射21天后,檢測(cè)陰莖海綿體內(nèi)壓及頸動(dòng)脈壓,結(jié)果顯示:BCNI+Ad-Myocd大鼠ICP檢測(cè)較BCNI+Ad-vector組的顯著增高(P0.05),差異有統(tǒng)計(jì)學(xué)意義,但AICP/MAP仍低于NC組(P0.05)。HE染色可見,BCNI大鼠較NC大鼠陰莖組織平滑肌肌層變薄、細(xì)胞排列紊亂、內(nèi)皮不連續(xù),且BCNI+Ad-vector組更為嚴(yán)重;Masson染色可見平滑肌/纖維比率在BCNI大鼠中降低,且BCNI+Ad-vector組更為顯著(P0.05)。免疫組化可見與BCNI+Ad-vector組對(duì)比,Myocardin及α-sma在NC組及BCNI+Ad-Myocd大鼠中表達(dá)顯著增加(P0.05)。western blot檢測(cè),Myocardin治療后的BCNI大鼠陰莖海綿體平滑肌組織a-sma、calponin、Myocardin蛋白表達(dá)較BCNI+Ad-vector組明顯上調(diào),OPN明顯下調(diào)。結(jié)論1.BCNI大鼠發(fā)生勃起功能障礙,但早期BCNI大鼠陰莖海綿體平滑肌并無(wú)發(fā)生組織學(xué)變化。2.BCNI大鼠陰莖海綿體平滑肌細(xì)胞在造模后第5天發(fā)生表型轉(zhuǎn)化。3.Myocardin基因治療可以恢復(fù)BCNI大鼠部分勃起功能。4.Myocardin基因治療可以維持BCNI大鼠陰莖海綿體平滑肌細(xì)胞的收縮表型。綜合上述,我們得出:Myocardin基因通過(guò)維持陰莖海綿體平滑肌細(xì)胞的收縮表型,從而改善雙側(cè)海綿體神經(jīng)損傷大鼠勃起功能。
[Abstract]:Background and objective radicalprostatectomy (RP) is a first-line treatment for localized prostate cancer, but the incidence of ED (RP-ED) is as high as 30%-87%. after operation. The pathological mechanism of RP-ED is not clear, and the treatment effect on type 5 phosphodiesterase inhibitor (phosphodiesterase 5 inhibitor, PDE5i) is not good. Different functions, the process of smooth muscle cells transformed from contractile type to proliferative type is called phenotypic transformation. Our previous study confirmed the phenotypic transformation of the cavernous smooth muscle cells in the penis of diabetic rats, and the close correlation with ED in diabetic rats was an important regulatory factor in the phenotype regulation of smooth muscle cells. The test group has confirmed that Myocardin gene therapy can improve the penile erectile function of diabetic rats. The aim of this study is to establish the bilateral cavernous nerve injury (BCNI) rat, to determine whether the phallic smooth muscle cells of the cavernous corpus cavernosum of the BCNI rats have phenotypic transformation, and to explore the pathological mechanism of ED in BCNI rats, and to try to find out the pathological mechanism of the ED in BCNI rats. Method 1. the erectile function of BCNI rats was improved by Myocardin gene. Methods the phenotypic characteristics of the cavernous smooth muscle cells in the cavernous corpus cavernosum of rats were established to establish bilateral cavernous nerve injury rats and 36 sham groups. The erectile function of the BCNI and NC groups was detected on 3,5,7 days, and the maximum penile corpus cavernosum stimulation pressure / average was calculated. Intraeavemous pressure/mean arterial pressure (CP/MAP) and the expression of a-SMA, calponin, Myocardin, OPN protein in the middle segment of the penis, calponin, Myocardin, OPN protein. The effect of the erectile function and the phenotypic transformation of the penile cavernous smooth muscle cells (cavernous smooth muscle cells) in 30 SD rats were divided into 3 groups, namely, group BCNI+Ad-Myocardin, group BCNI+Ad-vector and group NC+PBS, to construct Myocardin gene adenovirus, and the purified Myocardin adenovirus was introduced into the cavernous cavernous cavernous body of BCNI rats, and the internal pressure of the cavernous corpus cavernosum in each group was detected after 21 days of injection. Western blot was used to detect the expression of a-SMA, calponin, Myocardin, OPN protein in the middle section of the penis. In addition, HE staining, Masson staining and immunohistochemistry and detection of the morphological changes of the penis and the results of smooth muscle content in the first chapter: 3 days, 5 days, and 7 days, the internal pressure and neck movement of the penis corpus cavernosum were measured. The method of pulse pressure was used to evaluate the erectile function of rats. The results of ICP and MAP showed that ICP and AICP/MAP in BCNI rats were significantly lower than those in the NC group (P0.05), and Western blot detected the a-SMA in the tissue of the cavernosum of the penis of the fifth days of the BCNI rats. There was no significant difference in the number and shape of smooth muscle of BCNI rats and NC rats in HE staining and Masson staining. Second: after 21 days of injection, the internal pressure of cavernosum and carotid pressure in the penis were detected. The results showed that the ICP detection in BCNI+Ad-Myocd rats was significantly higher than that in the BCNI+Ad-vector group (P0.05), but the difference was statistically significant, but AICP was statistically significant. /MAP was still lower than group NC (P0.05).HE staining. Compared with NC rats, the smooth muscle layer of the penis tissue was thinner, the cell arrangement was disorderly, the endothelial discontinuity was discontinuous, and the BCNI+Ad-vector group was more serious; Masson staining showed that the ratio of smooth muscle / fiber was decreased in BCNI rats, and BCNI+ Ad-vector group was more significant (P0.05). Immunohistochemical staining can be seen and observed. In group tor, the expression of Myocardin and alpha -sma in NC and BCNI+Ad-Myocd rats increased significantly (P0.05).Western blot detection. The smooth muscle tissue of the cavernous corpus cavernosum was a-SMA, calponin, and obviously down regulated in the BCNI rats after Myocardin treatment. Conclusion erectile dysfunction occurred in the rats. But there is no histological change in the smooth muscle of the cavernous corpus cavernosum in the early BCNI rats. The phallic smooth muscle cells of the cavernous corpus cavernosum in the.2.BCNI rat fifth days after the model transformation, the.3.Myocardin gene therapy can restore the BCNI rat's partial erectile function.4.Myocardin gene therapy can maintain the contraction of the smooth muscle cells of the corpus cavernosum of the BCNI rat In general, we conclude that the Myocardin gene can improve the erectile function of the bilateral cavernous nerve injury by maintaining the contractile phenotype of the cavernous smooth muscle cells of the penis.
【學(xué)位授予單位】：南方醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：R698.1

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本文編號(hào)：1903342