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1.
糖尿病大鼠阴茎海绵体组织nNOS神经变化的实验研究   总被引:6,自引:3,他引:6  
目的 :研究糖尿病对大鼠阴茎海绵体组织nNOS神经纤维的影响。 方法 :34只SD雄性大鼠分为 6周组(17只 )和 8周组 (17只 ) ,其中每组各 11只腹腔注射链脲佐菌素制备糖尿病模型 ,其余各 6只注射柠檬酸缓冲液作为空白对照 ,分别在注射 6周和 8周后 ,观察大鼠阴茎勃起功能 ,并采用免疫组化SP法检测糖尿病大鼠阴茎组织nNOS神经纤维的数量。 结果 :2组糖尿病大鼠的阴茎勃起率分别为 37.5 %和 14 .3% ,差异有显著性 (P <0 .0 5 ) ,均明显低于对照组 (P <0 .0 1)。 2组糖尿病大鼠nNOS神经纤维的表达明显低于对照组 (P <0 .0 1)。 8周组中糖尿病大鼠阴茎的勃起功能和nNOS神经纤维的数量明显低于 6周组 ,分别为 (37.6 0± 6 .76 )条和 (2 8.0 0±5 .2 9)条 ,即随着病程的延长 ,勃起功能和nNOS神经纤维的表达下降 (P <0 .0 5 ) ,而对照组大鼠nNOS神经纤维的数量差异无显著性 [(83.0 0± 3.2 2 )vs(81.0 0± 3.6 1) ]。 结论 :糖尿病严重影响勃起功能和nNOS神经纤维的表达。糖尿病大鼠阴茎海绵体组织中nNOS神经纤维的数量明显减少 ,且与病程正相关 ,这可能是糖尿病性勃起功能障碍的发病机理之一。  相似文献   

2.
目的 :研究抗高血压药物对自发性高血压大鼠 (SHR)勃起功能和神经元型一氧化氮合酶 (nNOS)神经纤维的影响。 方法 :18只 6周龄雄性SHR随机均分为 3组 :缬沙坦 [30mg (kg·d) ]干预组、螺内酯 [2 0mg (kg·d) ]干预组和对照组。 12周后 ,观察大鼠阴茎勃起功能 ,并用免疫组化SP法检测阴茎组织中nNOS神经纤维的数目。 结果 :缬沙坦干预组勃起次数与另外两组相比差异有显著性 (P <0 .0 5 ) ,后两组之间差异无显著性 (P >0 .0 5 ) ,勃起率 3组之间差异不明显 (P >0 .0 5 ) ,阴茎组织中nNOS神经纤维数目 ,两干预组与对照组之间差异有显著性 (P <0 .0 1) ,而两干预组之间差异无显著性 (P >0 .0 5 )。 结论 :缬沙坦能改善SHR的勃起功能 ,而螺内酯无改善作用 ,这种差异与nNOS神经纤维数目无关 ,可能与血管紧张素Ⅱ(AngⅡ)受体阻滞剂引起血管重构等其他作用有关  相似文献   

3.
目的 研究髂内动脉结扎对大鼠阴茎海绵体组织神经型一氧化氮合酶(nNOS)神经纤维及内皮型一氧化氮合酶(eNOS)表达的影响。方法 45只Wistar雄性成年大鼠随机分为假手术组(21只)和手术组(24只)。其中手术组采用双侧髂内动脉结扎的方法制备动脉性勃起功能障碍(ED)大鼠模型,假手术组作为对照组只切开腹腔不结扎髂内动脉。于术后1周、3周、6周末分别取各组1/3大鼠,观察其勃起功能,并采用免疫组化SP法检测大鼠阴茎组织中nNOS神经纤维的数量及eNOS的表达。结果 手术组与假手术组相比,1周末、3周末和6周末在阴茎勃起次数和阴茎组织nNOS神经纤维数量及eNOS表达上均有显著差异(P<0.01)。手术组大鼠阴茎勃起次数3周末高于1周末,6周末高于3周末;eNOS的表达3周末明显低于1周末,而6周末高于3周末,差异均有显著性意义(P<0.001),并呈增加趋势。手术组大鼠阴茎组织nNOS神经纤维数量三者之间差异均有显著性(P<0.001),呈进行性下降。结论 髂内动脉结扎影响阴茎勃起功能和nNOS、eNOS的表达。阴茎组织中nNOS阳性神经纤维数量的减少,可能是髂内动脉结扎术后阴茎勃起功能障碍发生的原因之一。  相似文献   

4.
衰老对大鼠阴茎海绵体NOS I的表达和NOS活性的影响   总被引:2,自引:4,他引:2  
目的 :探讨衰老对大鼠阴茎海绵体一氧化氮合酶Ⅰ (NOSⅠ)mRNA、蛋白的表达和NOS活性的影响。 方法 :30只雄性SD大鼠按不同月龄分为成年组、老年组和衰老组 ,应用Western印迹、RT PCR方法分别检测不同年龄组阴茎海绵体NOSⅠ蛋白及mRNA的表达 ;用紫外分光光度计测定不同年龄组阴茎海绵体NOS的活性。 结果 :成年组NOSⅠ 蛋白的表达量最高 ,老年组和衰老组显著降低 ,分别为成年组的 75 .6 %和 6 1.2 % ;NOSⅠmRNA的表达与蛋白表达的变化一致 ;老年组NOS活性与成年组差异无显著性 (P >0 .0 5 ) ,衰老组NOS活性明显降低 ,是成年组的70 .4 % ,并且差异非常显著 (P <0 .0 1)。 结论 :衰老引起NOSⅠ 蛋白及mRNA的表达降低和NOS活性的显著降低 ,可能是老年性阴茎勃起功能障碍的主要机制之一。  相似文献   

5.
目的:探讨NOS/NO、HO/CO、RhoA/Rho激酶等信号通路在自发性高血压大鼠(SHR)阴茎海绵体中的表达及相互关系。方法:健康成年雄性SPF级SHR与对照组WKY大鼠各7只,16周龄,体重250~300g。麻醉后颈动脉和海绵体内插管连续监测平均动脉压(MAP)和海绵体内压(ICP)。利用电刺激海绵体神经,记录ICP/MAP比值变化。利用免疫组化和Western印迹方法分析ROCK2、HO-2、eNOS在阴茎海绵体中的表达变化。结果:SHR组在利用电刺激海绵体神经后ICP/MAP比值升高不明显(P>0.05),海绵体组织中ROCK2蛋白表达水平升高显著(P=0.017),HO-2表达水平则降低显著(P=0.006)。HO-2主要位于阴茎海绵体的平滑肌细胞及神经细胞内,eNOS则主要位于阴茎海绵体血管内皮细胞,两者在SHR组表达明显降低。结论:NOS/NO、HO/CO、RhoA/Rho激酶与SHRED有关,并且可能互相影响。  相似文献   

6.
目的:本研究通过检测糖尿病性勃起功能障碍(ED)大鼠阴茎组织中神经生长因子(NGF)表达,并使用hNGF进行治疗,以探讨糖尿病性ED发病机制及NGF治疗作用的机制。方法:成年雄性SD大鼠60只,随机取50只大鼠用于制作糖尿病模型,饲养8周后,取正常组和糖尿病组大鼠阴茎海绵体组织,采用RT-PCR和W estern印迹法检测NGF的mRNA及蛋白水平。从造模成功的糖尿病大鼠中筛选出有ED大鼠,把所有大鼠分为5组:正常组、糖尿病性ED组、糖尿病性ED单用NGF组(NGF组)、糖尿病性ED单用胰岛素组(R I组)、糖尿病性ED联合应用NGF和胰岛素组(NGF+R I组,胰岛素通过颈部皮下注射给药,NGF通过腹腔内注射给药),8周后测海绵体内压(ICP),并取所有大鼠阴茎海绵体组织用免疫组化法观察nNOS神经纤维的变化。结果:与正常组相比,糖尿病性ED组大鼠阴茎海绵体组织中NGF的mRNA表达增加,蛋白含量增加。与糖尿病性ED组相比,NGF组、R I组、NGF+R I组ICP水平显著升高(P<0.05);NGF组、R I组、NGF+R I组阴茎组织中nNOS神经纤维水平显著升高(P<0.05)。结论:糖尿病晚期勃起神经出现损伤并发生ED,推测可能与NGF分泌增加的幅度小于高血糖状态对勃起神经的损伤程度有关,也可能与NGF与其相应受体结合转运能力损害有关,给予外源性NGF可能有助于糖尿病性ED局部神经病变减轻和勃起功能改善。提示NGF的异常在糖尿病性ED的发病及治疗中可能具有重要作用。  相似文献   

7.
大鼠阴茎组织中NOS表达及增龄的影响   总被引:5,自引:1,他引:5  
为探讨大鼠阴茎组织中一氧化氮合酶分布及增龄对其的影响。本文采用NADPHd组化对不同月龄大鼠阴茎组织进行染色。结果显示NOS主要分布于大鼠阴茎组织平滑肌细胞,而内皮和社会纤维含量较少;随年龄增加,阴茎组织中NOS表达逐渐减弱,各月龄组间差别明显。  相似文献   

8.
目的:研究生长激素(GH)对老年大鼠勃起功能及阴茎组织中神经型一氧化氮合酶(nNOS)神经纤维的影 响。 方法:24只老年(18月龄)雄性SD大鼠随机均分为对照组和GH处理组。GH处理组大鼠每天后肢皮下注 射重组人GH(rhGH)200μg,对照组注射生理盐水0.2ml,共3周。于第4、8周末分别取各组1/2大鼠,颈部皮下 注射阿朴吗啡(APO)评价其勃起功能,免疫组化SP法检测大鼠阴茎组织中nNOS神经纤维的数量。 结果:4周 末,GH处理组大鼠的勃起功能和nNOS神经纤维数量与对照组相比,差异均无显著性(P>0.05)。8周末,GH处 理组大鼠仅勃起次数有上升,与对照组相比差异有显著性(P<0.05),勃起率无明显改变;而阴茎组织中nNOS神 经纤维数量,GH处理组大鼠有明显的上升,对照组大鼠无明显改变,两组相比,差异有极显著性(P<0.01)。 结 论:GH促进了老年大鼠阴茎组织中nNOS神经纤维的再生,并在一定程度上改善了老年大鼠的勃起功能。  相似文献   

9.
史俊萍 《中华男科学杂志》2006,12(12):1123-1124,1127
阴茎勃起功能障碍(ED)是糖尿病(DM)常见的并发症之一,国外报道DM性ED发病率为50%~75%,其发病机制尚不清楚。勃起是一种神经控制的血流动力学变化过程,盆神经节控制进入阴茎的血流。本研究通过建立DM大鼠模型,检测盆神经节神经元型一氧化氮合酶(nNOS)的表达和海绵体NOS的活性,以进一步探讨DM性ED的发病机制。  相似文献   

10.
目的:探讨慢性肾功能衰竭(CRF)性勃起功能障碍(ED)的发病机制。方法:应用SD雄性大鼠分两期行5/6肾脏切除术,建立CRF动物模型。将假手术组(NCRF组,n=30)、CRF模型大鼠(CRF组,n=45)分别随机均分为Ⅰ(2周)、Ⅱ(4周)、Ⅲ(6周)3组,并分别于2、4、6周注射阿朴吗啡(APO,80μg/kg)后观察大鼠阴茎勃起情况,筛选CRF性ED模型大鼠;测定阴茎海绵体组织一氧化氮合酶(NOS)的活性,及其组织的M asson染色图像分析。结果:CRF性ED大鼠阴茎海绵体组织NOS活性及平滑肌面积显著降低(P<0.01或P<0.05),胶原纤维略有增加,且上述变化与CRF病程密切相关。海绵窦血管腔无明显变化。结论:CRF严重影响阴茎勃起功能,阴茎海绵体组织NOS活性降低及阴茎海绵体平滑肌面积的减少可能是其重要的发病机制。  相似文献   

11.
Objective: To investigate the alterations in nNOS containing nerve fibers in corpus cavernosum of spontaneous hypertension rats (SHR). Methods: Twelve male SHR and 12 male WKY rats, both aged 6 weeks, were separately divided into 4- and 12-week observation groups at random. At the end of the observation period, the erectile function was assessed and the number of cavernosal nNOS containing nerve fibers determined. Results: Significant differences existed in the erection frequency and the number of nNOS containing nerve fibers between the SHR rats and the WKY controls (P< 0.01); there was also a significant difference in the numbers of nNOS containing nerve fibers between the SHR 4- and 12-week observation groups (P<0.05). Conclusion: The erectile function and the number of nNOS containing nerve fibers were significantly reduced in SHR rats. The decrease in nNOS containing nerve fibers may be one of the mechanisms underlying erectile dysfunction in hypertensive rats.  相似文献   

12.
目的:探讨高血压对大鼠阴茎海绵体组织胱硫醚-γ-裂解酶(CSE)和胱硫醚-β-合成酶(CBS)表达的影响及与大鼠勃起功能的关系。方法:健康雄性SPF级自发性高血压大鼠(SHR)与对照组WKY(Wistar-Kyoto)大鼠各10只,于12周龄时测定大鼠血清睾酮、阴茎海绵体内压/平均动脉压(ICP/MAP)、血浆和阴茎海绵体内源性H2S的含量,采用免疫组化和Western印迹分析CSE和CBS在阴茎海绵体内的表达。结果:SHR与WKY大鼠的血清睾酮值没有显著差别,SHR的ICP/MAP在0、3和5 V电刺激盆腔神经节(MPG)时均显著低于WKY组(n=10,P0.05)。SHR血浆H2S含量显著低于WKY大鼠[(10.49±1.35)μmol/Lvs(21.92±2.75)μmol/L,P0.05],SHR阴茎海绵体组织内源性H2S含量显著低于WKY大鼠[(52.60±3.44)nmol/mg prot vs(87.67±2.12)nmol/mg prot,P0.05],SHR阴茎海绵体组织内源性H2S生成率也较WKY大鼠显著降低[(1.14±0.07)nmol/(mg·min)vs(4.35±0.32)nmol/(mg·min),P0.05]。CSE及CBS主要表达在SHR和WKY大鼠阴茎海绵体平滑肌细胞和血管内皮细胞的胞质,SHR的CSE及CBS蛋白表达量均显著低于WKY大鼠(P0.05)。ICP/MAP与CSE和CBS表达呈高度正相关(r=0.955、0.977,P均0.05)。结论:高血压大鼠阴茎海绵体组织中CBS和CSE的表达下降,导致阴茎海绵体内H2S合成减少,可能是高血压引起勃起功能下降的机制之一。  相似文献   

13.
The aim of this study was to investigate the relationship between sulphur dioxide (SO2) signalling pathway and the changes in erectile function under low androgen levels. Thirty‐six healthy male Sprague Dawley (SD) rats aged eight weeks were randomly divided into androgen replacement group, castration group and sham group. Rats in the androgen replacement group were subcutaneously injected with testosterone propionate at 3 mg/kg every other day postcastration. The maximum intracavernous pressure/mean arterial pressure (ICPmax/MAP) and the relative content of SO2 in the penile corpus cavernosum were measured. The mRNA and protein expressions of aspartate aminotransferase (AAT1 and AAT2), cysteine oxidase (CDO), endothelial nitric oxide synthase (eNOS) and phosphorylation of endothelial nitric oxide synthase (P‐eNOS) were detected. ICPmax/MAP, P‐eNOS/eNOS and the level of SO2 decreased significantly in the castration group compared to the other groups (p < 0.05). The expressions of mRNA and protein decreased significantly in the castration group compared to the androgen replacement group and the sham group (p < 0.05), while there was no significant difference between the androgen replacement group and sham group. Low androgen levels can inhibit erectile function by downregulating the SO2 signalling pathway.  相似文献   

14.
目的:了解磷酸化Erk1/2(P-Erk1/2)和磷酸化Akt1(P-Akt1)在自发性高血压大鼠(SHR)和正常血压大鼠阴茎海绵体中的表达及与勃起功能的关系。方法:健康成年雄性SPF级SHR与对照组WKY大鼠各8只,14周龄,体重250~300g。麻醉后颈动脉和海绵体内插管连续监测平均动脉压(MAP)和海绵体内压(ICP),利用电刺激海绵体神经,记录ICP/MAP比值变化;免疫组织化学及RT-PCR技术检测P-Erk1/2和P-Akt1在大鼠阴茎海绵体的表达。结果:3V和5V电刺激海绵体神经后SHR组ICP/MAP比值(0.26±0.06、0.28±0.04)均较WKY组(0.46±0.12、0.76±0.13)显著降低(P均<0.05),P-Erk1、P-Erk2mRNA和P-Erk1/2蛋白的相对表达量在SHR组(0.81±0.05、0.91±0.06、54.22±10.05)较WKY组(0.42±0.04、0.68±0.14、7.05±1.45)显著升高(P均<0.05);P-Akt1mRNA和P-Akt1蛋白的相对表达量在SHR组(0.90±0.05、11.17±2.21)与WKY组(0.92±0.06、10.91±1.86)无显著差异(P均>0.05)。结论:高血压性勃起功能障碍的发生与阴茎海绵体P-Erk1/2的过度表达有关,而与P-Akt1的表达水平无明显相关。  相似文献   

15.

OBJECTIVE

To study the effect of the H2S‐donating derivative of sildenafil (ACS6) compared to sildenafil citrate and sodium hydrosulphide (NaHS) on relaxation, superoxide formation and NADPH oxidase and type 5 phosphodiesterase (PDE5) expression in isolated rabbit cavernosal tissue and smooth muscle cells (CSMCs), and in vivo on indices of oxidative stress induced with buthionine sulphoximine (BSO).

MATERIALS AND METHODS

Relaxation was studied in an organ bath in response to carbachol and after incubation with interleukin‐1β for 12 h. CSMCs were incubated with tumour‐necrosis factor‐α or the thromboxane A2 (TXA2) analogue, U46619, with or with no sildenafil citrate, ACS6 or NaHS for 16 h. Superoxide formation and the expression of p47phox (an active subunit of the NADPH oxidase complex) and PDE5 protein was then assessed using Western blotting. Rats were also treated with BSO (with or with no sildenafil citrate or ACS6) for 7 days; cavernosal cGMP, cAMP, glutathionine and plasma TXA2 and 8‐isoprostane F was measured by enzyme‐linked immunosorbent assay.

RESULTS

ACS6 and sildenafil citrate relaxed cavernosal smooth muscle equipotently; NaHS alone had little effect at up to 100 µm . The formation of superoxide and expression of p47phox and PDE5 was reduced by ACS6, sildenafil citrate and NaHS (order of potency: ACS6 > sildenafil citrate > NaHS). The effects of ACS6 were blocked by inhibitors of protein kinase A (PKA) and PKG. In rats treated with BSO, both ASC6 and sildenafil citrate reduced the increased plasma levels of TXA2 and 8‐isoprostane F but increased cGMP, cAMP and glutathionine levels in corpus cavernosum.

CONCLUSIONS

By virtue of a dual action on PKA and PKG activation, ACS6 not only promotes erection, acutely, but might also have a long‐term beneficial effect through inhibition of oxidative stress and downregulation of PDE5.  相似文献   

16.
OBJECTIVES: To clarify the pharmacological effects of adrenomedullin, a potent vasodilator and hypotensive peptide isolated from human phaeochromocytoma cells, on corpus cavernosal smooth muscle in vitro, as the intracavernosal injection of adrenomedullin induces penile erection in the anaesthetized cat. MATERIALS AND METHODS: The effects of adrenomedullin were investigated in isolated muscle strips from New Zealand rabbit corpus cavernosum smooth muscle pre-contracted with phenylephrine alone, in the presence of indomethacin (cyclooxygenase inhibitor), Nomega-nitro l-arginine methyl ester (L-NAME, a nitric oxide synthase inhibitor), and K+-channel blockers. RESULTS: Adrenomedullin caused relaxation of isolated pre-contracted rabbit corpus cavernosum strips in a concentration-dependent manner. The response of corpus cavernosum was unaffected L-NAME, indomethacin and K+-channel blockers. CONCLUSION: The relaxation exerted by adrenomedullin in rabbit corporal tissue may arise from the effect of the drug on its specific receptors and/or calcitonin gene-related peptide-1 receptors. The relaxant effect of adrenomedullin might lead to novel clinical applications for erectile dysfunction.  相似文献   

17.
S. He  T. Zhang  Y. Liu  L. Liu  H. Zhang  F. Chen  A. Wei 《Andrologia》2015,47(3):303-309
This study aimed to investigate whether gene transfer of myocardin to the penis of diabetic rats can modulate corpus cavernosum smooth muscle (CCSM) cells phenotype and restore erectile function. Five normal control rats, and 22 diabetic rats were randomly divided into four groups: rats transfected with adCMV‐myocardin (N = 6), treated with empty vector (N = 6), injected with medium (N = 5), and sham‐operated rats (N = 5). The erectile response was measured 7 days after transfection. The percent of smooth muscle and the expressions of SMα‐actin, smooth muscle myosin heavy chain (SMMHC), calponin were evaluated. The increases in intracorporal pressure(ICP)/mean arterial pressure and total ICP in response to nerve stimulation in the adCMV‐myocardin treated rats were significantly greater than those in the empty vector (P < 0.001 and < 0.001), medium only (< 0.001 and < 0.001), and sham‐operated rats (< 0.001 and < 0.001). The suppressed expressions of SMα‐actin, SMMHC and calponin were completely restored, and the amount of smooth muscle in diabetic rats were not restored after treatment. It is concluded that myocardin ameliorated erectile responses in diabetic rats mainly via promoting phenotypic modulation of CCSM cells from a proliferative to a contractile state.  相似文献   

18.
目的:检测去势大鼠阴茎海绵体中血红素加氧酶2(HO-2)/CO的表达,初步探讨勃起功能障碍(ED)的发病机制。方法:雄性SD大鼠72只均分为对照组、假手术组、去势组和去势锌原卟啉(Zn PP,HO阻断剂)组,检测基础条件和阿扑吗啡(APO)刺激后的海绵体内压(ICP)和勃起率;激光共聚焦显微镜检测大鼠勃起不同时期阴茎海绵体组织中HO-2蛋白的表达,分光光度计测定CO在大鼠勃起不同时期的含量。结果:基础条件和APO刺激后ICP和勃起率,去势组[(11.68±0.69)mm Hg,(54.81±3.86)mm Hg,33.3%]和去势Zn PP组[(11.20±0.71)mm Hg,(41.17±5.41)mm Hg,22.2%],与对照组[(22.83±2.66)mm Hg,(66.92±7.77)mm Hg,100%]和假手术组[(23.35±2.22)mm Hg,(70.43±7.22)mm Hg,100%]比较显著下降(P均0.01),且APO刺激后去势Zn PP组ICP较去势组明显降低(P0.01)。APO刺激后,勃起前和勃起中阴茎海绵体HO-2蛋白表达,去势组(445.4±23.7,847.4±35.0)和去势Zn PP组(390.1±29.7,526.0±52.5)较对照组(512.7±57.4,1 145.2±89.8)和假手术组(583.7±8.0,1 016.3±79.8)显著下降(P0.05或P0.01),且勃起中去势Zn PP组HO-2蛋白表达较去势组明显降低(P0.01);勃起后各组之间的HO-2蛋白表达变化差异无显著性。勃起前、中和后阴茎海绵体CO含量,去势组[(20.59±1.01)×10-7nmol/L,(32.53±1.26)×10-7nmol/L,(18.71±1.22)×10-7nmol/L]和去势Zn PP组[(12.52±1.05)×10-7nmol/L,(21.90±1.02)×10-7nmol/L,(16.56±0.55)×10-7nmol/L]较对照组[(26.76±1.41)×10-7nmol/L,(48.25±1.01)×10-7nmol/L,(27.10±1.58)×10-7nmol/L]和假手术组[(25.41±2.09)×10-7nmol/L,(47.90±1.22)×10-7nmol/L,(25.67±1.20)×10-7nmol/L]显著下降(P0.05或P0.01),且勃起中去势Zn PP组CO含量较去势组明显下降(P0.01)。结论:HO-2和CO表达下降与去势大鼠ED的发生有关。  相似文献   

19.
目的:研究淫羊藿苷是否通过调节核因子类红细胞2-相关因子2(NRF2)通路改善自发性高血压大鼠(SHR)的勃起功能.方法:随机将10周龄健康雄性WKY大鼠(WKR)与雄性SHR大鼠分为4组(每组6只,共24只):WKY对照组、WKR+淫羊藿苷组[10 mg/(kg·d)灌胃]、SHR对照组,SHR+淫羊藿苷组[10 m...  相似文献   

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