低强度体外冲击波治疗勃起功能障碍的临床疗效及机制的初步研究

发布时间：2018-03-02 17:29

本文选题：低强度体外冲击波　切入点：阴茎勃起功能障碍　出处：《苏州大学》2016年博士论文　论文类型：学位论文

【摘要】：第一部分低强度体外冲击波治疗勃起功能障碍的临床疗效初步观察目的临床观察低强度体外冲击波(low intensity extracorporeal shock wave therapy,LI-ESWT)治疗勃起功能障碍的疗效和安全性。方法采用LI-ESWT治疗ED患者104例,包括心理性ED、器质性ED和混合性ED。患者平均年龄38.5岁,病程3个月,IIEF-5评分22分。随机分为试验组和对照组,各52例。试验组采用CS-2012A-9型体外冲击波骨科治疗机,低强度体外冲击波的探头在ED患者的阴茎的5个不同位置治疗,降低能量至工作电压5Kv,能量密度0.09MJ/mm2,频率120次/min,每个部位300冲击波治疗。每周治疗2次,连续治疗3周,停止治疗3周,然后每周治疗2次,连续治疗3周,共9周。对照组采用安慰治疗(使用相同的治疗仪,治疗步骤与治疗组相同,治疗探头不发出冲击波,但会发出相同的声音)。受试者经LI-ESWT治疗后评估SEP3、IIEF-ED评分以及EHS评分,同时记录不良反应事件发生。结果低强度体外冲击波治疗后,心理性ED SEP3从46.05%提高到84.29%,IIEF-ED评分从14.14分提高到20.90分;器质性ED SEP3从19.41%提高到53.45%,IIEF-ED评分从8.18分提高到14.86分;混合性ED SEP3从12.29%提高到51.33%,IIEF-ED评分从6.67分提高到14.67分,且差异均具有统计学意义(P0.05)。而对照组差异无统计学意义(P0.05)。接受LI-ESWT治疗后,试验组心理性ED、器质性ED、混合性ED阴茎勃起硬度评分均较治疗前有显著的提高,且差异均具有统计学意义(P0.05);对照组心理性ED、器质性ED、混合性ED EHS差异均无统计学意义。按照ED程度分别统计,接受LI-ESWT治疗后,试验组轻度ED SEP3从45.76%提高到82.33%,IIEF-ED评分从14.14分提高到20.62分;中度ED SEP3从34.25%提高到62.83%,IIEF-ED评分从10.08分提高到16.83分;重度ED SEP3从6.63%提高到48.68%,IIEF-ED评分从6.26分提高到13.84分,且差异均具有统计学意义(P0.05);对照组轻度ED、中度ED、重度ED SEP3、IIEF-ED评分差异均无统计学意义。接受LI-ESWT治疗后,试验组轻度ED、中度ED、重度ED阴茎勃起硬度评分均较治疗前有提高,且差异均具有统计学意义(P0.05);对照组轻度ED、中度ED、重度ED阴茎勃起硬度评分差异均无统计学意义。按照病程统计,接受LI-ESWT治疗后,试验组ED病史1年SEP3从45.43%提高到82.57%,IIEF-ED评分从13.95分提高到20.67分;ED病史1年SEP3从17.55%提高到54%,IIEF-ED评分从7.87分提高到14.97分;且差异均具有统计学意义(P0.05);对照组ED病史1年、ED病史1年差异均无统计学意义。接受LIESWT治疗后,试验组ED病史1年;ED病史1年阴茎勃起硬度评分均较治疗前有提高;且差异均具有统计学意义(P0.05);对照组ED病史1年、ED病史1年差异均无统计学意义。按照有无吸烟史统计,接受LI-ESWT治疗后,有吸烟史的试验组ED患者SEP3从25.27%提高到30.24%,IIEF-ED评分从9.60分提高到15.87分;无吸烟史的试验组ED患者SEP3从59.60%提高到67.95%,IIEF-ED评分从10.62分提高到17.84分;且差异均具有统计学意义(P0.05);有吸烟史的对照组ED患者、无吸烟史的对照组ED患者治疗前后差异均无统计学意义。接受LI-ESWT治疗后,有吸烟史的试验组ED患者、无吸烟史的试验组ED患者阴茎勃起硬度评分均较治疗前有提高;且差异均具有统计学意义(P0.05);有吸烟史的对照组ED患者、无吸烟史的对照组ED患者治疗前后差异均无统计学意义。按照慢性病史统计,接受LI-ESWT治疗后,有高血压病史的试验组ED患者SEP3从18.35%提高到53.17%,IIEF-ED评分从7.83分提高到14.74分,阴茎勃起硬度评分较治疗前有提高,且差异均具有统计学意义(P0.05);无高血压病史的试验组ED患者SEP3从37.10%提高到75.34%,IIEF-ED评分从12.31分提高到19.28分,阴茎勃起硬度评分较治疗前有提高,且差异均具有统计学意义(P0.05);有高血压病史的对照组ED患者、无高血压病史的对照组ED患者治疗前后差异均无统计学意义。接受LI-ESWT治疗后,有糖尿病病史的试验组ED患者SEP3从9.69%提高到49%,IIEF-ED评分从6.69分提高到14分,阴茎勃起硬度评分较治疗前有提高,且差异均具有统计学意义(P0.05);无糖尿病病史的试验组ED患者SEP3从37.31%提高到72.89%,IIEF-ED评分从11.94分提高到18.72分,阴茎勃起硬度评分较治疗前有提高,且差异均具有统计学意义(P0.05);有糖尿病的对照组ED患者、无糖尿病的对照组ED患者治疗前后差异均无统计学意义。LI-ESWT治疗后无疼痛及其它不良反应发生。结论此临床研究表明LI-ESWT尤其对高血压、糖尿病引起的ED有一定的治疗效果。低强度体外冲击波是治疗勃起功能障碍安全与有效的方法之一。第二部分低强度体外冲击波对糖尿病性ED大鼠阴茎海绵体组织血管内皮细胞的影响目的:研究低强度体外冲击波对糖尿病性勃起功能障碍(ED)大鼠阴茎组织血管内皮细胞的影响。方法:6只SPF级雄性SD(Sprague Dawley)大鼠用链脲左菌素和阿朴吗啡诱导建立I型糖尿病性ED大鼠模型。之后把造模成功的糖尿病性ED大鼠随机分成DMED组(未治疗组)、DMED+LIESW组(低强度体外冲击波治疗组),冲击波探头作用于阴茎体,选用300次的体外冲击波,工作电压5Kv,每组均接受LIESW 3次/周,连续治疗2周,每组3只,取3只非糖尿病正常大鼠为对照。治疗结束后先比较各组大鼠的勃起次数;然后将各组大鼠处死并取阴茎组织进行石蜡包埋,采用免疫细胞荧光检测阴茎海绵体内皮细胞标志物CD31的表达;采用免疫组织化学方法检测各组大鼠阴茎组织中e NOS的表达情况。结果:DMED组勃起次数0.00±0.00,显著低于正常对照组1.50士0.84(P0.01),DM+LISW组勃起次数1.17士0.65,明显高于DMED组0.00±0.00(PO.01),低于正常对照组1.50士0.84(P0.01);正常SD大鼠阴茎海绵体组织未见CD31的表达;DMED组大鼠阴茎海绵体组织未见CD31的表达;DMED组大鼠经低强度体外冲击波治疗后阴茎海绵体组织可见绿色荧光的内皮细胞标志物CD31阳性表达。e NOS在各组大鼠阴茎组织中均有表达,DMED组表达水平显著低于正常对照组(P0.01),DM+LISW组表达水平明显高于DMED组(PO.01),但低于正常对照组(P0.01)。结论:低强度体外冲击波可能通过促进内皮细胞再生和增加阴茎组织中的e NOS的表达来改善勃起功能。第三部分低强度体外冲击波对体外培养的人脂肪间充质干细胞增殖的影响及其治疗ED机制的初步探讨目的:观察低能量体外冲击波(LESW)对体外培养的人脂肪组织间充质干细胞(ADASs)增殖活性的影响,初步探讨体外冲击波治疗男性勃起功能障碍(ED)的可能机制。方法:经腹部皮下脂肪,获得人脂肪间充质干细胞。观察脂肪间充质干细胞在内皮细胞诱导体系中形态变化,通过免疫细胞化学方法及RT-PCR检测内皮细胞分化标志物。LESW冲击前后绘制细胞生长曲线,观察脂肪干细胞增殖活性的改变。结果:获得的人脂肪间充质干细胞,流式检测细胞高表达CD105、CD90;低表达CD34、CD45;脂肪间充质干细胞在内皮细胞诱导体系中形态发生一系列变化,脂肪间充质干细胞向内皮细胞诱导分化后表达CD31、CD34、Ⅷ因子、VE-cadherin和内皮型一氧化氮合成酶等内皮细胞特异性抗原;LESW能促进脂肪间充质干细胞的增殖,且能量密度为0.09MJ/mm2,300次冲击波的作用后细胞增殖更加明显。结论:实验分离获得的脂肪间充质干细胞,在体外实验观察其可以向内皮细胞分化。低强度体外冲击波可能通过诱导脂肪间充质干细胞的增殖,脂肪间充质干细胞可能向内皮细胞分化,进而治疗男性勃起功能障碍。
[Abstract]:The first part of the clinical curative effect of low intensity of extracorporeal shock wave therapy for erectile dysfunction Objective To observe the clinical preliminary observation of low intensity of extracorporeal shock wave (low intensity extracorporeal shock wave therapy, LI-ESWT) efficacy and safety in the treatment of erectile dysfunction. Methods 104 cases of LI-ESWT patients with ED, including psychological ED, organic ED and mixed ED. patients with an average age of 38.5 years, the duration of 3 months, IIEF-5 score of 22 were randomly divided into experimental group and control group, 52 cases in each. The experimental group was treated by CS-2012A-9 type extracorporeal shock wave department of orthopedics treatment machine, low intensity of extracorporeal shock wave probe in 5 different positions in the treatment of ED's penis, reduce the energy to work the energy density of 0.09MJ/mm2, voltage 5Kv, frequency 120 /min, each part of the 300 shock wave treatment 2 times a week for 3 consecutive weeks, stop for 3 weeks, and 2 treatments per week, for 3 weeks, A total of 9 weeks. The control group with placebo (using the treatment, the same treatment steps with the same treatment group, the therapeutic probe emits shock wave, but will sound the same voice). The subjects treated with LI-ESWT assessment SEP3, IIEF-ED score and EHS score, and record adverse events. Results low the strength of extracorporeal shock wave therapy after psychological ED SEP3 increased from 46.05% to 84.29%, IIEF-ED score improved from 14.14 to 20.90; the organic ED SEP3 increased from 19.41% to 53.45%, IIEF-ED score improved from 8.18 to 14.86; the mixed ED SEP3 increased from 12.29% to 51.33%, IIEF-ED score improved from 6.67 to 14.67 points, and the differences were statistically significant (P0.05). While the control group had no significant difference (P0.05). The experimental group received LI-ESWT treatment, psychological ED, organic ED, mixed ED erectile stiffness scores were significant To improve, and the differences were statistically significant (P0.05); the control group psychological ED, organic ED, mixed ED EHS. There were no significant differences in statistics in accordance with the degree of ED were treated with LI-ESWT, experimental group ED SEP3 slightly increased from 45.76% to 82.33%, IIEF-ED score improved from 14.14 to 20.62 moderate ED; SEP3 increased from 34.25% to 62.83%, IIEF-ED score improved from 10.08 to 16.83; severe ED SEP3 increased from 6.63% to 48.68%, the IIEF-ED score improved from 6.26 points to 13.84 points, and the differences were statistically significant (P0.05); control group, mild ED, moderate ED and severe ED SEP3 IIEF-ED score the difference was not statistically significant. After LI-ESWT therapy, the experimental group of mild ED, moderate ED and severe ED penile erection hardness scores were improved, and the differences were statistically significant (P0.05); control group, mild ED, moderate ED and severe ED penile erection hardness rating The difference was not statistically significant. According to disease statistics, treated with LI-ESWT, experimental group ED 1 year history of SEP3 increased from 45.43% to 82.57%, IIEF-ED score improved from 13.95 to 20.67; ED is a 1 year history of SEP3 increased from 17.55% to 54%, IIEF-ED score improved from 7.87 to 14.97; and the difference is statistical significance (P0.05); control group ED 1 years history and the history of ED for 1 years. There were no significant differences in LIESWT after treatment, the test group ED 1 year history of ED; a 1 year history of penile erection hardness scores were improved; and the differences were statistically significant (P0.05); control group ED 1 years history and the history of ED for 1 years. There were no significant differences in smoking history statistics, treated with LI-ESWT, ED of the experimental group of SEP3 patients with a history of smoking increased from 25.27% to 30.24%, IIEF-ED score improved from 9.60 to 15.87; no smoking history of the test group ED from 59 patients with SEP3 Up to 67.95%.60%, the IIEF-ED score improved from 10.62 to 17.84; and the difference was statistically significant (P0.05); the control group of ED patients with a history of smoking, history of smoking control group after treatment of ED patients. There were no significant differences in LI-ESWT treated group, with a history of smoking test in patients with ED. The test group ED patients with erectile hardness score no smoking history than before treatment was improved; and the differences were statistically significant (P0.05); the control group of ED patients with a history of smoking, history of smoking control group after ED treatment there were no significant differences. According to the statistics of chronic disease treated with LI-ESWT ED, experimental group SEP3 patients with a history of hypertension increased from 18.35% to 53.17%, the IIEF-ED score improved from 7.83 points to 14.74 points, the penis erects hardness score before treatment were improved, and the differences were statistically significant (P0.05); hypertension The test group ED patients with a history of SEP3 increased from 37.10% to 75.34%, the IIEF-ED score improved from 12.31 points to 19.28 points, the penis erects hardness score before treatment were improved, and the differences were statistically significant (P0.05); the control group of ED patients with hypertension and non hypertension control group before and after treatment with ED were no statistically significant. After LI-ESWT, the test group ED SEP3 patients with a history of diabetes increased from 9.69% to 49%, the IIEF-ED score improved from 6.69 points to 14 points, the penis erects hardness score before treatment were improved, and the differences were statistically significant (P0.05); group ED patients without a history of diabetes from SEP3 37.31% to 72.89%, the IIEF-ED score improved from 11.94 points to 18.72 points, the penis erects hardness score before treatment were improved, and the differences were statistically significant (P0.05); diabetic control group ED patients without diabetes. No pain and other adverse reactions in the control group before and after treatment with ED had no significant difference after.LI-ESWT treatment. Conclusion the clinical study showed that LI-ESWT especially for hypertension, diabetes caused by ED have a certain therapeutic effect. The low intensity of extracorporeal shock wave therapy for erectile dysfunction is one of the safe and effective methods. The second part of low intensity effect of extracorporeal shock wave on diabetic vascular endothelial cells ED rat penile tissue Objective: To study the low intensity of extracorporeal shock wave on diabetic erectile dysfunction (ED) effects of vascular endothelial cells in rat penile tissue. Methods: 6 SPF male SD (Sprague Dawley) in rats with streptozotocin and the establishment of ED of apomorphine induced type I diabetes rat model. After the successful model of diabetic ED rats were randomly divided into DMED group (treatment group), group DMED+LIESW (low intensity Extracorporeal shock wave therapy group), shock wave probe acting on the body of the penis, extracorporeal shock wave 300 times, working voltage of 5Kv, each group received LIESW 3 times / week, for 2 weeks, 3 rats in each group, 3 rats in nondiabetic rats as control. After the end of treatment were compared to rats erection times; and then the rats were sacrificed and the penile tissue were embedded in paraffin, using immunofluorescence cell corpus cavernosum endothelial cell marker CD31 expression; expression by immunohistochemistry method to detect rat penile tissue e NOS. Results: DMED group of 0 + 0 times of erection, was significantly lower than that of the normal control group is 1.50 + 0.84 (P0.01), DM+LISW group of 1.17 erectile times + 0.65, 0 + 0 was significantly higher than that of DMED group (PO.01), lower than the normal control group is 1.50 + 0.84 (P0.01); the expression of SD in normal rat penile tissue was CD31; DMED rats There was no CD31 expression in corpus cavernosum; DMED rats after low intensity extracorporeal shock CD31 positive expression of.E NOS in penile tissue of rats in each group were expressed in corpus cavernosum visible green fluorescence in the endothelial cell marker wave after the treatment, the expression level of DMED group was significantly lower than the normal control group (P0.01), the expression level of DM+LISW group obviously higher than that of DMED group (PO.01), but lower than the normal control group (P0.01). Conclusion: low intensity extracorporeal shock wave may improve the erectile function by promoting the expression of endothelial cell regeneration and increase in penile tissue e NOS. A preliminary discussion of the third part of low intensity effect of extracorporeal shock wave on cultured human adipose derived mesenchymal stem cell proliferation and its mechanism of treatment of ED Objective: To observe the effect of low energy extracorporeal shock wave (LESW) on cultured human adipose tissue derived mesenchymal stem cells (ADASs) proliferation, preliminary study Extracorporeal shock wave therapy for erectile dysfunction (ED) and the possible mechanism. Methods: the abdominal subcutaneous fat, get human adipose derived mesenchymal stem cells. Observation of adipose derived mesenchymal stem cells induced morphological changes in the system in endothelial cells by immunocytochemical method and RT-PCR detection of endothelial cell differentiation markers before and after.LESW impact rendering the cell growth curve, cell proliferation was observed. Results: the fat stem of human adipose derived mesenchymal stem cells was detected by flow cytometry, the high expression of CD105, CD90; low expression of CD34 and CD45; adipose derived mesenchymal stem cells induced by the system in a series of morphological changes in endothelial cells, adipose derived mesenchymal stem the expression of CD31 cells differentiated into endothelial cells after CD34, factor VIII, VE-cadherin and endothelial nitric oxide synthase of endothelial cell specific antigen; LESW can promote adipose mesenchymal stem cell proliferation, and can Volume density is 0.09MJ/mm2300 times the effect of shock wave after the cell proliferation is more obvious. Conclusion: isolated adipose derived mesenchymal stem cells in experimental observation, which can differentiate into endothelial cells in vitro. The low intensity of extracorporeal shock wave could induce adipose derived mesenchymal stem cells proliferation, adipose mesenchymal stem cells to differentiate into endothelial cells, and the treatment of male erectile dysfunction.

【学位授予单位】：苏州大学
【学位级别】：博士
【学位授予年份】：2016
【分类号】：R698.1

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