【作者】 蒋玉清；

【导师】 蔡文清；

【作者基本信息】 河北医科大学 ， 外科学， 2014， 博士

【摘要】 第一部分良性前列腺增生症伴组织学炎症相关因素分析目的:分析比较前列腺增生患者合并组织学前列腺炎与单纯前列腺增生患者的相关因素，为临床治疗提供可行的依据。方法:将因尿潴留或LUTS而行TURP的60位住院患者，根据组织病理学诊断，分为前列腺增生合并前列腺炎组45例和单纯前列腺增生组15例，术前对患者年龄、尿潴留史、合并症、国际前列腺症状评分(IPSS)、生活质量评分（QOL）、前列腺体积、残余尿量、最大尿流率Qmax、PSA、血清C反应蛋白(CRP)、血液中白细胞总数、尿液中白细胞计数等分别认真检测并详细记录。结果:1两组患者合并症比较：单纯BPH组有尿潴留病史患者例数（2/15，13%）低于前列腺增生合并炎症组（18/45，40%）（P <0.05）；并且单纯BPH组中合并糖尿病患者例数（3/15，20%）低于炎症组（18/45，40%）（P <0.05），合并高血压在BPH组（7/15，47%），BPH合并炎症组（20/45，44%），合并冠心病在BPH组（4/15，27%），BPH合并炎症组（8/45，18%），合并高脂血症在BPH组（6/15，40%），BPH合并炎症组（17/45，38%），两组之间无统计学差异（P>0.05）。2两组患者一般资料比较：两组患者平均年龄之间有统计学差异，其中单纯BPH组年龄（69.5±5.4）高于炎症组（63.4±3.8）（P <0.05）；炎症组IPSS和QOL评分（28.6±5.2，5.2±0.8）高于单纯BPH组（23.7±4.5，4.2±1.3）（P <0.05），BPH合并炎症组病例残余尿RUV（249.6±14.9ml）、最大尿流率Qmax（5.2±2.4）、前列腺体积（66.8±21.3ml）与BPH组相比(157.5±21.1ml，7.8±2.1ml/s，54.4±18.7ml)均有统计学差异（P<0.05），其中炎症组病例残余尿及前列腺体积均大于单纯增生组，而最大尿流率低于单纯增生组。3两组患者血PSA.CRP及血尿白细胞计数比较：BPH合并炎症组PSA和CRP（5.3±2.1ng/L，4.4±2.7mg/L）高于BPH组（3.1±1.2ng/L，0.2±1.30mg/L），BPH合并炎症组血尿常规白细胞计数(5.1±2.1×109/L，2.8±1.3/HP)与BPH组（4.6±1.9×109/L，2.6±1.5/HP）比较无统计学差异（P>0.05）。结论:1合并前列腺组织学炎症的前列腺增生患者，其尿潴留发生率，前列腺体积，IPSS,QOL评分，血PSA等均明显高于单纯增生组，提示前列腺炎可能促进前列腺增生的发展进程。2血C反应蛋白（CRP）作为可选择性的血清标志物，术前检测CRP可间接了解前列腺增生症是否合并前列腺炎。3炎症组中糖尿病发生率升高，提示代谢性疾病可能与前列腺增生合并前列腺炎有某些相关性。第二部分促炎症细胞因子在前列腺增生症伴组织学炎症中表达的研究目的:探讨患者前列腺组织及血清中肿瘤坏死因子α(TNF-α)、白细胞介素6(IL-6)以及CD3的表达及临床意义。方法:60名因尿潴留或LUTS行TURP手术的BPH患者，根据病理诊断分为单纯前列腺增生组（15例）及前列腺中增生合并单纯前列腺炎组（45例），分组与第一部分相同。收集患者一般资料，TURP术中取前列腺组织,立即放入液氮灌中，转-80C°低温冰箱中保存，两组病例标本分别采用蛋白印迹方法（western-blotting）测定组织中TNF-α、IL-6以及CD3的含量。术前空腹抽取静脉血3ml，ELISA测定血清中TNF-α、IL-6的含量，并应用免疫组织化学方法定位检测TNF-α、IL-6以及CD3在前列腺组织中的表达定位情况。结果:免疫组织化学染色结果显示BPH合并炎症组TNF-α、IL-6、CD3表达MOD值（0.0524±0.04，0.0334±0.024，0.0365±0.009）高于BPH组（0.0323±0.6，0.204±0.016，0.0223±0.003），western-blot方法检测结果显示BPH合并炎症组TNF-α、IL-6、CD3表达相对量(0.24±0.04，0.07±0.04，0.33±0.09)高于BPH组(0.19±0.06，0.04±0.02，0.27±0.06)，ELISA结果亦显示BPH合并炎症组血清中TNF-α、IL-6浓度(34.92±5.1ng/ml，22.07±14.32ng/ml)高于BPH组(24.05±11.5ng/ml，11.05±3.45ng/ml)。尿潴留组各促炎症细胞因子含量明显高于LUTS组，高IPSS评分组各促炎症细胞因子含量高于低IPSS评分组。前列腺增生症合并不同程度炎症之间各促炎症细胞因子亦存在统计学差异，以重度炎症升高最为显著。结论:前列腺增生合并前列腺炎时，局部前列腺组织中TNF-α、IL-6、CD3含量均升高，血清中TNF-α及IL-6亦升高，尿潴留及高IPSS评分时前列腺局部组织及血清中TNF-α及IL-6均升高，提示炎症刺激下促炎因子表达明显增多，使前列腺上皮及间质细胞增殖，导致前列腺体积增大，促进临床症状进展。TNF-α、IL-6、CD3可作为评价下尿路症状病情程度的分子生物学指标。第三部分热休克蛋白27在前列腺增生伴组织学炎症中的表达研究目的:讨前列腺增生症合并炎症患者前列腺组织及血清中热休克蛋白27表达及临床意义。方法:60名TURP手术的BPH患者，分为单纯前列腺增生组（15例）及前列腺中增生合并单纯前列腺炎组（45例），分组同第一部分，收集患者一般资料，TURP术中取前列腺组织，立即放入液氮灌中，后转入-80C°低温冰箱中保存，采用western-blotting测定组织中HSP27的含量，ELISA测定血清中HSP27的含量，并应用免疫组织化学方法定位检测HSP27在前列腺组织中的表达定位情况。比较HSP27的表达在前列腺增生合并炎症组与单纯前列腺增生组，尿潴留组和LUTS组，高IPSS和低IPSS组的差异，不同程度炎症组之间差异，并与TNF-α、IL-6、CD3表达进行相关性分析。结果:1免疫组织化学染色方法显示，前列腺增生合并组织学炎症组中HSP27MOD值（0.0574±0.13）高于单纯增生组（0.0427±0.062），在尿潴留组中MOD值（0.0596±0.012）高于LUTS组（0.0236±0.04），在高IPSS组中（0.0545±0.014）高于低LUTS组（0.0321±0.12）。统计学有显著性差异。（P <0.01）。前列腺增生合并不同程度炎症之间亦存在统计学差异，以重度炎症升高最为显著。HSF27表达升高与TNF-α、IL-6表达有关。2western-blotting方法结果显示，HSP27在炎症组中测定值（0.41±0.13）高于单纯增生组（0.27±0.06），在尿潴留组中测定值为（0.44±0.12）高于LUTS组（0.23±0.04），HSP27在高IPSS组（0.45±0.14）高于低LUTS组（0.21±0.12）。3ELISA测定血清中HSP27浓度，在炎症组（156.86±64.4ng/ml）高于单纯增生组（97.10±48.19ng/ml），在尿潴留组（144.65±45.28ng/ml）高于LUTS组（102.28±50.37ng/ml），在高IPSS组（146.23±38.57ng/ml）高于低LUTS组（103.48±53.82ng/ml）。差异有统计学意义。（P<0.05）。结论:1前列腺增生合并前列腺炎组前列腺组织及血清中HSP27含量高于单纯增生组,尿潴留组及高IPSS组亦高于LUTS组及低IPSS组，说明小分子HSP27可能作为分子伴侣在炎症反应刺激下促使前列腺增生症病程进展，并出现相应的临床症状。2前列腺增生合并组织学炎症时HSP27的升高与促炎症因子TNF-α及IL-6的升高有明显相关性，并且尿潴留时，HSP27升高与TNF-α、IL-6升高亦有明显相关性，说明在前列腺增生合并慢性炎症的发病机制中，HSP27与促炎症细胞因子可能存在相互诱导的关系，其分子学信号传导途径有待进一步研究。更多还原

【Abstract】 PART Relative factor analysis of benign prostatic hyperplasiaassociated with histological prostatitisObjective： To provide feasible basis for clinical treatment throughanalysing and comparing relative factors of patients with benign prostatichyperplasia, and patients with benign prostatic hyperplasia and histologicalprostatitis.Methods： According to histopathological diagnosis, hospitalizedpatients(60cases) were divided into two groups,prostatic hyperplasia withprostatitis group (45cases) and BPH group(15cases). These60cases werereceived TURP surgical treatment due to urinary retention or LUTS.All dataincluding the patients’ age, history of urinary retention, complications, theinternational prostate symptom score (IPSS), quality of life score (QOL), andprostate volume, residual urine volume, maximum urine flow rate (Qmax),PSA, serum c-reactive protein (CRP), the total number of white blood cells inthe blood, white blood cell count in urine and other clinical parameters werecollected and compared.Results：1Comparing two groups of patients with complications: the cases(2/15,13%) with a history of urinary retention in simple BPH group werelower than the cases (18/45,40%) in BPH with inflammation group (P <0.05);the cases of diabetes mellitus in group of simple BPH patients weresignificantly lower than inflammation group (P <0.05), and othercomplications such as hypertension, coronary heart disease andhyperlipidemia between the two groups had no significant difference (P>0.05). 2General data comparison in two groups of patients: there weresignificant differences between two groups of patients in average age, Theaverage age among BPH patient was higher than that in BPH withinflammation group (P<0.05); IPSS and QOL score in inflammation groupwas higher than the score in BPH group (P<0.05), RUV, maximum urinaryflow rate (Qmax) and residual urine prostatic volume had significantdifference (P<0.05) between the two groups, the average residual urine andprostate volume in inflammation group were greater than BPH group, and themaximum urine flow rate was lower than that in BPH group.3Comparison of the PSA,CRP level and leucocyte counts in blood andurine in two groups: the leucocyte counts in the routine examination of bloodand urine between the two groups was no significant difference (P>0.05);The level of PSA and CRP in BPH with prostatic inflammation groupwere higher than that in simple BPH group (P<0.05).Conclusions：1The incidence of urinary retention, prostate volume, IPSS, QOL score,the level of blood PSA in BPH with histological prostatitis group weresignificantly higher than that of simple BPH. Prostatitis may promote theclinical progress of BPH, and increase the chance of surgical treatment inpatients with BPH.2Elevation of plasma C-reactive protein level in BPHwith prostatitisindicates prostatitis may be a systemic inflammatory response, CRP can beused as a clinical preoperative serum marker of selectivity of the existence ofprostatitis.3The increased incidence of diabetes mellitus in BPH with prosttitisindicated that metabolic disease may have a promoting effect on BPH withprostatitis.Part Ⅱ Association and expression study of proinflammatorycytokins in BPH with prostatitisObjective: To study the expression and clinical significance ofproinflammatory cytokins:tumor necrosis factor alpha (TNF-α), interleukin6 (IL-6) and CD3in prostate tissue and serum in60cases which received TURPsurgical treatment due to urinary retention or LUTS.Methods:60patients who received TURP surgery for urinary retentionor LUTS BPH patients, divided into BPH group (15cases) and BPH withprostatitis group (45cases), The patients’s general information were collected.Prostate tissue was obtained from the transition zone of the urethra duringTURP process,then immediately stored in the-80°c condition. Tumor necrosisfactor alpha (TNF-α), interleukin6(IL-6), and the content of CD3detectedthrough western blot method in prostate tissue and enzyme-linkedimmunosorbent assay (ELISA) in serum.and tumor necrosis factor alpha(TNF-α), the levels of interleukin6(IL-6). And expression of TNF-α, IL-6andCD3were detected through immunohistochemical method to insure site ofthese in prostate tissue.The BPH and BPH with prostatitis groups,urinaryretention and LUTS groups, high IPSS and low IPSS groups were compared inthe expression of TNF-α,IL-6,CD3in prostatic tissue and plasma.Results: Expression of TNF-α,IL-6,CD3in BPH with histologicalinflammation group is significantly higher than that in BPH. Proinflammatorycytokins levels in urinary retention group was significantly higher than thatof LUTS group, Expression of TNF-α,IL-6,CD3in high IPSS group (IPSS>25)was higher than low IPSS group(IPSS19-25). Expression of TNF-α,IL-6,CD3among Mild, moderate, severe inflammation in BPH also had significantlystatistical differences.Expression of TNF-α,IL-6,CD3in severe inflammationin BPH was highest.Conclusion: TNF-α,IL–6,CD3levels increased in BPH with prostatitis inlocal prostate tissue, the serum TNF–α and IL-6also increased. TNF-α,IL–6levels also increased in the urinary retention and high IPSS score groups inlocal prostate tissue and serum. Proinflammatory factor,TNF-α and IL-6,CD3were significantly increased in inflammatory stimuli reaction, they mayparticipate in the pathogenesis of chronic inflammation in prostate hyperplasiaand was induced by proinflammatory factor they could be used as evaluationof molecular biology in low urinary tract symptoms. Part Ⅲ Association and expression study of heat shock protein27inBPH with prostatitisObjective: To study the expression and clinical significance of heatshock protein27in prostate tissue and serum of patients in BPH and BPHwith prostatitis groupsMethods:60patients who received TURP surgery for urinary retentionor LUTS BPH patients, divided into BPH group (15cases) and BPH withprostatitis group (45cases).Prostate tissue was obtained from the transitionzone of the urethra during TURP process,then immediately stored in the-80°ccondition.HSP27was detected through western blot andimmunohistochemical staining methods in prostate tissue and enzyme-linkedimmunosorbent assay (ELISA) in serum.The BPH and BPH with prostatitisgroups,urinary retention and LUTS groups, high IPSS and low IPSS groupswere compared in the expression of HSP27in prostatic tissue and plasma.Thecorrelation analysis of the expression of HSP27with TNF-alpha, IL-6,CD3was underwent in BPH and BPH with prostatitis groups.Results: Expression of HSP27in BPH with histological inflammationgroup was significantly higher than that in BPH. HSP27levels in urinaryretention group was significantly higher than that of LUTS group, Expressionof HSP27in high IPSS group (IPSS>25) was higher than low IPSSgroup(IPSS19-25).Expression of HSP27among Mild, moderate, severeinflammation in BPH also had significantly statistical differences.Expressionof HSP27in severe inflammation in BPH was highest in three different degreeinflammation.Conclusions:1HSP27expression in BPH with prostatitis group was higher than that ofBPH group, and it in urinary retention and high IPSS group was higher thanthat in LUTS group and the low IPSS group, small molecule HSP27may be asa molecular chaperone to participate in the pathogenesis of inflammationstimulation to the prostate in BPH clinical symptoms progress.2The rise of TNF-α,IL-6,CD3in BPH with prostatitis had obviously correlation with HSP27.The molecular signaling pathway was needed furtherresearched about the relationship between HSP27and proinflammatoryfactors.更多还原