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The Influence of Depression on Benign Prostatic Hyperplasia in Rats
文章更新时间:2006-11-26  

Introduction
Benign prostatic hyperplasia(BPH) could be frequently seen in gerontic male, and BPH severally influenced people’s quality of life[1],[2]. At present, it is unclear of the BPH’s etiological factor, and the latest researches were focused in Hormone themry, Stem cell themry, and response between Base-epithelia themry. Now, there were many experiment researches on the influences of rat’s BPH brought by muti-factors, however, there was no cover of the influence of rat’s BPH brought by depression. Then this research would study the role of depression in rat’s BPH.
1. Materials and Methods
1.1 Animal 40 male sprague-dawleg (SD) rats, whose weight were 220~230g, were bought from national institute for the control of phamaceutical and biological products. Rats were specefic pathogen free animal (SPF), without special pathogen。The number of certificate is SCXK(beijing)2002-0003。All the rats were growed in SPF environment, whose temperature was 21-22℃,and moisture was 40-50%. The rats were 12 hours in light and 12 hours in dark, everyday. The rats were grown in cages, and they could freely eat high nutrien feed and drink sterile water. And experiments were made in animal lab of Xuanwu Hospital, Capital University of Medical.

1.2 Physic Testosterone propionic (TP) is bought from the Shanghai No. 9 pharmaceutical factory, whose batch number was 970302115. Proliferating cell nuclear antigen (PCNA) and Immune-histochemistry streptavidin/peroxidase kit were bought from Beijin zhongshan biotechnology company limited.

1.3 Experiment Method
1.3.1 Make models All the rats were randomly divided into 4 different groups: normal control group (n=11), depression group (n=10), Testosterone propionic (TP) group (n=11), and depression+TP group (n=8). In TP group and depression+TP group, every rat was given TP 1mg/d subcutaneous injection (TP is solved into soy, 2mg/mL), so the injection quantity was 0.5mL. And the injection continued 3 weeks. Normal control group and depression group were injected the equivalence solvent. On the other hand, every rat in depression group and depression+TP group was induced a red loop, which was fixed around the neck of rat[3]. Loops were made of red lucite, which had 2cm inside diameter and 10cm outside diameter,and whose thickness is 0.5cm. The loops were fixed by screws, which could be used to just their diameters, so they could be appropriately fixed around rats’ necks. Then, the loops were reserved for 3 weeks.
1.3.2 Estimate Marker After models were made 3 weeks, we killed all rats and weigh the mass of their bodies and prostates. Then, we computed the prostate index (prostate weight/body weight×1000).
1.3.3 Histology Observation All the samples were fixed by 10% formalin, embedded by paraffin, filleted in 5μm, stained by Haematine-Eosin (HE) and immunohistochemistry method, and marked PCNA. Immunohistochemistry was used streptavidin/peroxidase method, DAB to show color, and haematine to re-dye nuclei. Every sample was made 5 sections, in every staining. We continuously observed 10 sights, computed the number of positive PCNA cells in 100 prostatic epithelial cell of every sight, and used their average value as PCNA multiplication index[3].

1.4 Statistics Treatment We used ±s to show every group’s value. And, we used t test and mono-factor analysis of variance (least-significant Duncan, LSD) to check infra-groups’ differences. Libin and Chen wenqiang, traditional Chinese medicine department of XuanWu hospital, analyzed all the data.

2 Result
2.1 The Influences of Depression and TP to Rats’ Prostatic Hyperplasia The prostate weight and prostate index of depression group were significantly higher than normal control group (t=-2.155,p=0.044; t=-6.609,p=0.000), and the prostate weight and prostate index of testosterone propionaste group were significantly higher than normal control group (t=-5.508,p=0.000; t=-6.227,p=0.000), which showed that depression and testosterone propionaste could significantly induce rats’ prostatic hyperplasia. The prostate weight and prostate index of testosterone propionaste group were significantly higher than depression group(t=-5.071, P=0.000; t=-3.444, p=0.004), which showed that testosterone propionaste could more significantly induce rats’ prostatic hyperplasia than depression. (table 1).

Table 1 The Influence of Depression and TP to Rats’ Prostatic Hyperplasia ( ±s)
GROUP N MASS OF PROSTAT PROSTATE INDEX
Normal Control 11 466.89±68.94 1.02± 0.16c )
Depression 10 529.71± 73.08a ) 1.39±0.20
Testosterone Propionaste 11 778.64±142.49b)d) 1.87±0.39b)d)
Depression+TP 8 776.21±122.91b)d) 2.03±0.32b)d)
Through t test, we found the significant difference between different groups. F=9.38,p=0.000,Compared with the normal control group: a) p<0.05; compared with depression group: b) p<0.05

3 Discussion
  In more than 100 years, there were two main factors that could be generally acknowledged, and they were: old-age and functional testis. Based on this doctrine, people provided many new themry. Prostatic interstitial and epidermic cell’s component could be changed with age, and the interaction between these two things was the mainly internal factor that induces to the prostate’s growth. In Claus’ research, he thought that urethra milieu area was BPH’s mainly origin area, and this area’s PCNA index was significantly higher than other areas, which shown that cellproliferation in this area was active[4]. And it means that the increase of cellproliferation is important in BPH’s occurrence and development. There are many factors, as race, environment, food, smoke, sex life, socioeconomic status, education, hypertension, and diabetes that could influence the BPH’s occurrence. Many literatures report that the descending of sperm’s number and quality, the descending of sexual function, and ascending of BPH is connected with the change of modern living environment, living pattern, living tempo, and eating habit, and some other changes, as acute social competition, increasing social pressure, and depressive state[5]. Some scholar thought that depression could influence internal milieu[6]. Because neurotransmitter and neurotrophic factor are prostate’s excitor substance, neurotransmitter could result in a series of signal convection in prostate smooth muscle cells, which would make smooth muscle shrink, and then influence miction response, or G protein signal convection that would result in prostatic hyperplasia[6]. There was research could prove that BPH patients often accompanied anxiety-depression of aniso-degree, especially those patients who accompanied with acute urinary retention. So, it is necessary to deal with patients’ psychologic obstacle, while treating their BPH[7],[8].

  Tradition Chinese medicine paid more attention to the influence of “seven emotion”. And, the locus of prostate is the local of TCM liver meridian of foot-jueyin. So, based on TCM theory and this basic pathogenesis, we decided to treat from patients’ liver, and then suggest dispersing stragnated liver, and dissipating phlegm and blood stasis to treat BPH. We researched a model, which was similar to the clinical illness and combined Chinese medicine syndrome and modern medicine disease, and discovered new examine marker to reveal the relationship of BPH and liver depression that could provide evidences to the research of parenchyma of stagnation of liver syndrome.

  The results of our experiment showed that there was no significant difference in the prostate weight, prostate index, tectology of prostate HE dying, and PCNA’s influence of prostate, between depression+ testosterone propionaste group and testosterone propionaste group, which means that there was not synergistic action between depression and testosterone propionaste (p>0.05). Testosterone propionaste had more fierce action than depression in inducing prostatic hyperplasia (p<0.01). But the depression group’s prostate weight, prostate index and PCNA proliferation index were significantly higher than the control group’s (p<0.05). Tectology of Haematine-Eosin dying showed that depression could transparently accelerate rats’ prostatic hyperplasia, however, the mechanism needs more research.

Referenced Literature
1、Zakaria L, Anastasiadis AG, Shabsigh R. Common conditions of the aging male: erectile dysfunction, benign prostatic hyperplasia, cardiovascular disease and depression. Int Urol Nephrol. 2001;33(2):283-92

2、Yubin, Zhanggen. 老年良性前列腺增生635例分类处理与提高患者生存质量的相关性分析. 中国临床康复,2002;6(4):609-610

3、Chenxiaoye. Utility TCM Syndrome Animal Model [M]. Beijing: Beijing Medical University &Peking Union Medical College Publishing house, 1993:260-263

4、Claus S,Berges R,Senge T et al.Cell kinetic in epithelium and stroma of benign prostatic hyperplasia.[J] Urol,1997,158:217-221

5、Quek KF, Low WY, Razack AH, Loh CS. The psychological effects of treatments for lower urinary tract symptoms. BJU Int. 2000;86(6):630-3

6、袁勇贵. 焦虑和抑郁障碍共病的研究现状. 中国临床康复,2002;6(17):2518-2519

7、刘贺亮,王禾,陈宝琦. 慢性前列腺炎患者生存质量及心理状态分析. 中国临床康复,2002;6(9):1314-1315

8、Clifford GM, Farmer RD. Drug or symptom-induced depression in men treated with alpha 1-blockers for benign prostatic hyperplasia? A nested case-control study. Pharmacoepidemiol Drug Saf. 2002 Jan-Feb;11(1):55-61


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