Ku Ja Hyeon, Kim Yoonjung, Moon Kyung Chul, Kim Yon Su, Kim Myung-Suk, Kim Hyeon Hoe, Paick Jae-Seung
Department of Urology, Seoul Veterans Hospital, Seoul, Korea.
J Urol. 2006 Sep;176(3):1230-5. doi: 10.1016/j.juro.2006.04.036.
We determined whether hepatocyte growth factor gene transfer after partial bladder outlet obstruction would prove effective for decreasing transforming growth factor-beta expression and consequently decreasing collagen deposition in partially obstructed rat bladders.
Ten-week-old male Sprague-Dawley rats were divided into 3 groups of 10 each, including group 1--sham operation, group 2--bladder outlet obstruction for 4 weeks and group 3--hepatocyte growth factor gene transfer after bladder outlet obstruction. Two weeks after the onset of bladder outlet obstruction in group 3 hepatocyte growth factor-liposome complex (50 microg human hepatocyte growth factor cDNA) was injected into the smooth muscle of the rats.
We noted no difference between groups 2 and 3 with regard to the ratio of bladder weight to body weight. The ratio in groups 2 and 3 was significantly higher than in group 1 (p = 0.043). The mean percent of collagen area +/- SE was 36.32% +/- 1.83%, 27.90% +/- 2.66% and 8.97% +/- 3.35% in groups 1 to 3, respectively (p <0.05). Relative hepatocyte growth factor and c-met mRNA and protein expression were higher in group 3 than in groups 1 and 2. However, the expression of transforming growth factor-beta1 mRNA and protein was higher in group 2 than in groups 1 and 3.
These findings may imply a possible novel therapeutic strategy against bladder dysfunction arising in patients with bladder outlet obstruction.
我们确定部分膀胱出口梗阻后肝细胞生长因子基因转移是否能有效降低转化生长因子-β的表达,从而减少部分梗阻大鼠膀胱中的胶原沉积。
将10周龄雄性Sprague-Dawley大鼠分为3组,每组10只,包括第1组——假手术组,第2组——膀胱出口梗阻4周组,第3组——膀胱出口梗阻后肝细胞生长因子基因转移组。在第3组膀胱出口梗阻开始2周后,将肝细胞生长因子-脂质体复合物(50微克人肝细胞生长因子cDNA)注入大鼠平滑肌。
我们发现第2组和第3组在膀胱重量与体重的比值方面没有差异。第2组和第3组的该比值显著高于第1组(p = 0.043)。第1至3组的胶原面积平均百分比±标准误分别为36.32%±1.83%、27.90%±2.66%和8.97%±3.35%(p <0.05)。第3组中相对肝细胞生长因子和c-met mRNA及蛋白表达高于第1组和第2组。然而,第2组中转化生长因子-β1 mRNA和蛋白的表达高于第1组和第3组。
这些发现可能暗示了一种针对膀胱出口梗阻患者出现的膀胱功能障碍的新型治疗策略。