引言
雖然良性攝護腺增生在中老年男性族 群十分常見，但其成因依舊未明。許多研究已顯示攝護腺疾病與血管疾病的危險因子出現與否有關，這些危險因子包括高血壓及糖尿病，並同時也暗示著循環異常。代謝性症候群是一群心血管疾病的危險因子之集合，而且在流行病學上，攝護腺增生被認為是代謝症候群的共病性之一。此外，慢性局部缺血會造成兔子及老鼠攝護腺平滑肌收縮增加及明顯的結構改變。因此，本實驗最主要的目的是要評估在人類及老鼠上，代謝症候群與良性攝護腺增生及攝護腺血流的關係，以及確認慢性缺血在此關係下所扮演的角色。引此，我們設計了前瞻性的臨床試驗及動物實驗來驗證我們的假設。

目標
1. 在患有攝護腺增生的病患，建立攝護腺血流、心血管疾病的危險因子數量及攝護腺大小之關係。
2. 建立代謝症候群的動物模型。
3. 了解代謝症候群老鼠之前列腺結構及生理變化，尤其血流及收縮力。

方法
1. 未曾服用甲型腎上腺激性拮抗劑或5α還原抑制劑或已停藥六個月的良性攝護腺增生的病人被篩選進入本實驗，經直腸超音波被用來測定攝護腺血流，同時記錄代謝症候群危險因子的數量及臨床表徵，最後將這些資料進行相關性的計算。
2. Wistar老鼠經由餵食高果糖飼料來誘發代謝症候群。正常老鼠與果糖飼養的代謝症候群老鼠被用來進行攝護腺組織學研究、量測攝護腺大小以及記錄攝護腺對甲型腎上腺激性刺激劑的反應，並使用雷射都普勒超音波來偵測老鼠攝護腺的血流及微循環。

結果
1. 130個有症狀的攝護腺肥大病患被選入，血管疾病的危險因子數量與尿道周圍動脈的阻力指數成中度相關 (Spearman’s correlation, r=0.228, p = 0.011)。此外，若將攝護腺攝體積分成小於20，20~40與大於40立方公分三組，則發現攝護腺體積越大者，其尿道周圍動脈的阻力指數越高 (0.57±0.014 vs 0.62±0.012 vs 0.66±0.031, one-way ANOVA, p=0.003)；同樣地，攝護腺移形區體積大於6立方公分的病患比移形區體積小於6立方公分的病患有較高的尿道周圍動脈的阻力指數 (0.65±0.015 vs 0.58±0.011, t test, p=0.002)。
2. 果糖飼養的代謝症候群老鼠與正常老鼠比較下，其有較大的攝護腺、攝護腺組織增生、對正腎上腺素的反應張力增加、較慢的攝護腺血流速以及較少的攝護腺血流量。

結論
從以上的發現，我們認為代謝症候群的危險因子會引起攝護腺灌流不足，以及引起人類與老鼠的攝護腺產生組織學上及生理上的變化，後者與攝護腺增生的表現類似。這些結果提供我們未來研究慢性缺血對攝護腺之影響的重要指引。

關鍵字: 代謝症候群、良性攝護腺增生、血流

Introduction
Although benign prostatic hyperplasia (BPH) is common in the elderly male population, the cause of BPH remains unclear. Several studies suggested an association between prostatic disease and the presence of risk factors of vascular disorders, such as hypertension or diabetes mellitus, implying circulatory disturbance. Metabolic syndrome is a constellation of multiple cardiovascular disease risk factors and BPH is supposed to be one of the sequelae in metabolic syndrome according to epidemiologic studies. Besides, chronic ischemia increases prostatic smooth muscle contraction and leads to marked prostatic structural changes in rats and rabbits. The aim of our study was to assess the effects of metabolic syndrome risk factors on BPH and prostatic blood flow. We thus conducted a clinical prospective study and animal study to test our hypothesis.
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Objective
1. To establish the relationships between the prostatic blood flow, the number of cardiovascular disorders and prostate size in human with clinical BPH.
2. To establish an animal model of metabolic syndrome.
3. To identify the structural and physiological changes in the prostate of rats with metabolic syndrome, especially prostatic blood flow and contractility

Material and method
1. Patients, who had not taken alpha-blockers or 5-alpha reductase inhibitors before examination for at least 6 month, with symptomatic BPH in NCKU urological OPD were enrolled in this study. Prostatic blood flow resistive index (RI) was detected by Doppler transurethral ultrasonography, and the numbers of metabolic syndrome risk factors, as well as clinical parameters, were collected and the correlations were analyzed.
2. Metabolic syndrome was induced in fructose-fed Wistar rats. Metabolic syndrome rats and control ones were used for histological studies and measurements of prostate size, as well contractile responses to alpha-adrenergic receptor agonist stimulation. Laser Doppler flowmetry was applied to detect blood flow and microcirculation of prostate in rats.

Results
1. One hundred and thirty patients with symptomatic BPH were enrolled and moderate correlation was found between the numbers of metabolic syndrome risk factors and the RI of periurethral arteries by Pearson’s correlation (Spearman’s correlation, r=0.228, p = 0.011). Besides, higher RI of periurethral arteries was found in patients with larger prostate (RI in patients with prostate volume <20 cm3 vs 20~40 cm3 vs >40 cm3 = 0.57±0.014 : 0.62±0.012 : 0.66±0.031, one-way ANOVA, p=0.003). Similarly, patients with transitional zone volume more than 6 cm3 had higher RI of periurethral arteries than those with transitional zone volume less than 6 cm3 (0.65±0.015 vs 0.58±0.011, t test, p=0.002)
2. Fructose-fed rats were a reliable animal model for induction of metabolic syndrome. The metabolic syndrome rats showed larger prostate with hyperplasia, more tension increases in response to phenylephrine stimulation, less flow volume and lower velocity of prostatic microcirculation. The findings suggested that metabolic syndrome induced prostatic hypoperfusion and prostatic structural / physiological changes mimicking human BPH.

Conclusions
Our findings suggest that the metabolic syndrome risk factors may induce prostatic hypoperfusion and histological / physiological changes in the prostates of human and rats, mimicking clinical BPH. The obtained information is useful for researches on the effect of chronic ischemia upon the prostate.

Key words
Metabolic syndrome, benign prostatic hyperplasia, blood flow

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