Prostates of rats with induced partial bladder outlet obstruction and the effect of Eviprostat on those changes

Prostatic inflammation plays a role in the progression of benign prostatic hyperplasia (BPH). Eviprostat is an antiinflammatory and antioxidant phytotherapeutic agent widely used to treat lower urinary tract symptoms in BPH. However, because Eviprostat is a mixture of compounds from multiple natural sources, its mechanism of action has been difficult to investigate. In this study, we used oligonucleotide microarrays to identify changes in gene expression that occur in the prostate of rats with surgically induced partial bladder outlet obstruction and the effect of Eviprostat on those changes. Male rats were divided into four groups of five or six animals each. The rats in groups 1 and 2 underwent a sham operation. Five days after the sham operation, group 1 was treated twice a day with vehicle (0.1% (w/v) Tween 80; sham/vehicle group) and group 2 was treated twice a day with 18 mg/kg Eviprostat (36 mg/kg daily; sham/Eviprostat group). The rats in groups 3 and 4 underwent surgical partial bladder outlet obstruction. Briefly, with the rat in the supine position, a midline suprapubic incision was made and the bilateral prostate was retracted to expose the neck of the bladder and the urethra, care being taken not to damage the bladder. The loose connective tissue at the base of the bladder was dissected away from the proximal urethra. A rubber ring was cut open and placed around the proximal urethra, and a 4-0 silk ligature was tied around the rubber ring. From the day after the operation, group 3 was treated twice a day for five days with vehicle (operated/vehicle group) and group 4 was treated twice a day for five days with 18 mg/kg Eviprostat (36 mg/kg daily; operated/Eviprostat group). On the sixth day, 2 h after the last administration, the rats were sacrificed and the prostate was rapidly removed.

前列腺炎症在良性前列腺增生（benign prostatic hyperplasia, BPH）的进展过程中具有一定作用。依普司他特（Eviprostat）是一种兼具抗炎与抗氧化活性的植物治疗剂，被广泛用于治疗良性前列腺增生引发的下尿路症状。然而，由于依普司他特（Eviprostat）是多种天然来源化合物的混合物，其作用机制一直难以探明。本研究采用寡核苷酸微阵列（oligonucleotide microarray）技术，鉴定手术诱导部分膀胱出口梗阻的大鼠前列腺组织的基因表达变化，并探究依普司他特（Eviprostat）对该类变化的调控效应。

实验选用雄性大鼠，将其分为四组，每组5~6只。第1组与第2组大鼠接受假手术处理。假术后第5天，第1组每日两次给予赋形剂（0.1% 质量体积比的吐温80（Tween 80）；假手术/赋形剂组），第2组每日两次给予18 mg/kg的依普司他特（Eviprostat）（每日总剂量36 mg/kg；假手术/依普司他特组）。

第3组与第4组大鼠接受手术诱导部分膀胱出口梗阻造模。具体操作如下：将大鼠置于仰卧位，于耻骨上正中做切口，牵拉双侧前列腺以暴露膀胱颈与尿道，操作过程中注意避免损伤膀胱；将膀胱基部的疏松结缔组织从近端尿道处分离；剪开橡胶环后套于近端尿道外，再以4-0丝线结扎橡胶环。自术后次日起，第3组每日两次给予赋形剂，连续给药5天（手术/赋形剂组）；第4组每日两次给予18 mg/kg的依普司他特（Eviprostat），连续给药5天（每日总剂量36 mg/kg；手术/依普司他特组）。

造模后第6天，末次给药2小时后处死大鼠，快速摘取前列腺组织。