热休克蛋白及促炎症细胞因子在前列腺增生合并前列腺炎发生中相关机制的研究

发布时间：2018-05-29 15:08

本文选题：前列腺增生 + 前列腺炎　；参考：《河北医科大学》2014年博士论文

【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（P0.05）。 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（P0.05），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（P0.05）。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。（P0.05）。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。
[Abstract]:Analysis of factors associated with histological inflammation in the first part of benign prostatic hyperplasia

Objective : To analyze the factors associated with histological prostatitis and benign prostatic hyperplasia in patients with benign prostatic hyperplasia ( BPH ) and to provide a feasible basis for clinical treatment .

Methods : Sixty - six patients who were hospitalized for the treatment of urinary retention or LUTS were randomly divided into four groups : prostate hyperplasia combined with prostatitis group ( 45 cases ) and simple benign prostatic hyperplasia group ( 15 cases ) , the age of the patient , the history of urinary retention , complications , international prostate symptom score ( IPSS ) , quality of life ( QOL ) , prostate volume , residual urine volume , maximum urine flow rate Qmax , PSA , serum C - reactive protein ( CRP ) , total white blood cell count , white blood cell count , etc . were carefully detected and recorded in detail .

Results :

The number of patients with simple BPH ( 2 / 15 , 13 % ) was lower than that in patients with benign prostatic hyperplasia ( 18 / 45 , 40 % ) ( P 0.05 ) .
The number of patients with diabetes mellitus ( 3 / 15 , 20 % ) was lower than that in the group of BPH ( 18 / 45 , 40 % ) ( P 0.05 ) . The combination of hypertension in BPH group ( 7 / 15 , 47 % ) , BPH combined with inflammation group ( 20 / 45 , 44 % ) , combined with coronary heart disease in BPH group ( 4 / 15 , 27 % ) , BPH combined inflammation group ( 8 / 45 , 38 % ) , and BPH combined inflammation group ( 17 / 45 , 38 % ) , there was no statistical difference between the two groups ( P0.05 ) .

The average age ( 69.5 卤 5.4 ) of the simple BPH group was higher than that in the inflammatory group ( 63.4 卤 3.8 ) ( P 0.05 ) .
The IPSS and QOL scores ( 28.6 卤 5.2 , 5.2 卤 0.8 ) in the inflammatory group were higher than those in the simple BPH group ( 23.7 卤 4.5 , 4.2 卤 1.3 ) ( P 0.05 ) , the residual urine RUV ( 249.6 卤 14.9 ml ) , the maximum urinary flow rate Qmax ( 5.2 卤 2.4 ) , the prostate volume ( 66.8 卤 21.3 ml ) and the BPH group ( 157.5 卤 21.1 ml , 7.8 卤 2.1 ml / s , 54.4 卤 18.7 ml ) were significantly higher than those in the BPH group ( 157.5 卤 21.1 ml , 7.8 卤 2.1 ml / s , 54.4 卤 18.7 ml ) .

The serum levels of PSA and CRP ( 5.3 卤 2.1 ng / L , 4.4 卤 2.7 mg / L ) in BPH combined with inflammatory group were higher than those in BPH group ( 3.1 卤 1.2 ng / L , 0.2 卤 1.30 mg / L ) . There was no statistical difference between the two groups ( 5.1 卤 2.1 脳 109 / L , 2.8 卤 1.3 / HP ) and BPH ( 4.6 卤 1.9 脳 109 / L , 2.6 卤 1.5 / HP ) ( P0.05 ) .

Conclusion :

1 . The incidence of urinary retention , prostate volume , IPSS , QOL and blood PSA were significantly higher in patients with benign prostatic hyperplasia combined with prostate histological inflammation than that in simple hyperplasia group , which suggested that prostatitis might promote the development of prostate hyperplasia .

Serum C - reactive protein ( CRP ) is used as a selectable serum marker , and CRP can be used to indirectly understand whether benign prostatic hyperplasia is combined with prostatitis .

The incidence of diabetes in the inflammatory group increased , suggesting that metabolic diseases may be associated with prostatic hyperplasia and prostatitis .

Expression of second partial pro - inflammatory cytokines in benign prostatic hyperplasia with histological inflammation

Objective : To investigate the expression and clinical significance of tumor necrosis factor 伪 ( TNF - 伪 ) , interleukin 6 ( IL - 6 ) and CD3 in patients with prostate tissue and serum .

Methods : 60 patients with BPH treated with uroschesis or LUTS were divided into simple benign prostatic hyperplasia group ( 15 cases ) and benign prostatic hyperplasia ( 45 cases ) according to the pathological diagnosis , and the contents of TNF - 伪 , IL - 6 and CD3 in the tissues were measured by western - blotting . The levels of TNF - 伪 , IL - 6 and CD3 in serum were measured by Western - blotting .

Results : The levels of TNF - 伪 , IL - 6 , CD3 in the patients with BPH were significantly higher than those in BPH group ( 0 . 0323 卤 0 . 6 , 0 . 204 卤 0 . 016 , 0 . 0223 卤 0 . 003 ) . The results showed that the levels of TNF - 伪 , IL - 6 , CD3 in the patients with BPH were significantly higher than those in BPH group ( 0 . 19 卤 0 . 06 , 0 . 04 卤 0 . 02 , 0 . 27 卤 0 . 06 ) .

Conclusion :

The levels of TNF - 伪 , IL - 6 and CD3 in local prostatic tissues increased , TNF - 伪 and IL - 6 in the serum increased , and TNF - 伪 and IL - 6 increased in the local prostate tissues , suggesting that the expression of TNF - 伪 , IL - 6 and TNF - 伪 and IL - 6 in the prostatic tissues and serum increased significantly , which led to the increase of prostate volume and the progression of clinical symptoms .

Expression of the third partial heat shock protein 27 in benign prostatic hyperplasia with histological inflammation

Objective : To investigate the expression and clinical significance of heat shock protein 27 in prostate tissue and serum of patients with benign prostatic hyperplasia complicated with inflammation .

Methods : 60 patients with BPH were divided into simple benign prostatic hyperplasia group ( 15 cases ) and benign prostatic hyperplasia combined with simple prostatitis group ( 45 cases ) .

Results :

The expression of HSP27MOD ( 0.074 卤 0.13 ) in benign prostatic hyperplasia combined with histological inflammation group was higher than that in simple hyperplasia group ( 0.0524 卤 0.062 ) , and the MOD value ( 0.0524 卤 0.012 ) was higher in the urinary retention group than in LUTS group ( 0.0236 卤 0.04 ) , which was higher in the high IPSS group than in the low LUTS group ( 0.0321 卤 0.12 ) . The expression of HSF27 was related to the expression of TNF - 伪 and IL - 6 .

The results showed that HSP27 was higher in the inflammatory group ( 0.41 卤 0.13 ) than in the simple hyperplasia group ( 0.27 卤 0.06 ) . The value of HSP27 in the urine retention group was ( 0.44 卤 0.12 ) higher than that in LUTS group ( 0.23 卤 0.04 ) , HSP27 was higher in the high IPSS group ( 0.45 卤 0.14 ) than in the low LUTS group ( 0.21 卤 0.12 ) .

The level of HSP27 in serum was higher than that in LUTS group ( 97.10 卤 48.19 ng / ml ) , and in the group of urinary retention ( 144.65 卤 45.28ng / ml ) was higher than that in LUTS group ( 102.28 卤 50.37 ng / ml ) , and in the high IPSS group ( 146.23 卤 38.57ng / ml ) was higher than that in the low LUTS group ( 106.23 卤 38.57ng / ml ) .

Conclusion :

The levels of HSP27 in prostate tissue and serum were higher than those in simple hyperplasia group , urinary retention group and high IPSS group than in LUTS group and low IPSS group .

There was a significant correlation between the increase of HSP27 and the increase of TNF - 伪 and IL - 6 in patients with benign prostatic hyperplasia complicated by histological inflammation , and the increase of HSP27 and TNF - 伪 and IL - 6 in the pathogenesis of benign prostatic hyperplasia combined with chronic inflammation indicated that there might be mutual induction between HSP27 and pro - inflammatory cytokines .
【学位授予单位】：河北医科大学
【学位级别】：博士
【学位授予年份】：2014
【分类号】：R697.3

【引证文献】