Elkelini Mohamed S, Aitken Karen, Bagli Darius J, Hassouna Magdy M
Surgery/Urology and Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada.
BJU Int. 2009 Feb;103(4):537-40. doi: 10.1111/j.1464-410X.2008.08131.x. Epub 2008 Oct 16.
To examine the voiding behaviour changes in rats with bladder outlet obstruction (BOO) while inhibiting matrix metalloproteinase (MMP) activity with doxycycline, as increased MMP activity may be involved in obstruction-induced bladder hypertrophy.
Female Sprague-Dawley were divided into eight groups (three rats in each group): normal control (NC) +/- doxycycline, 3 weeks partial BOO (3WPBOO) +/- doxycycline, 6 weeks PBOO +/- doxycycline, and 3 weeks PBOO followed by 3 weeks de-obstruction (3WOD) +/- doxycycline. All rats received the same food and water and were on the same 12 h dark/light cycle housed in metabolic cages. Treatment groups were given doxycycline 15 mg/kg/day subcutaneously twice daily. The voiding variables measured were average voided volume (AV V) and voiding frequency (VF) in 24 h. After completion of the voiding behaviour studies, the rats were killed and their bladders were excised and weighed.
The AV Vs were significantly increased (P < 0.05) in all study groups compared with the NC group except for the 3WPBOO-doxycycline and 3WOD-doxycycline groups. The VF was significantly increased (P < 0.05) only in the 3WOD-doxycycline group. The bladder weights were significantly increased after PBOO in all the study groups (P < 0.05), except for the 3WOD group.
These data show that MMP inhibition may affect voiding behaviour during the response to BOO or its relief. This is the first clinical demonstration that interfering with a principal target of bladder muscle wall remodelling may have a direct effect on bladder function.
研究膀胱出口梗阻（BOO）大鼠在使用强力霉素抑制基质金属蛋白酶（MMP）活性时的排尿行为变化，因为MMP活性增加可能与梗阻诱导的膀胱肥大有关。
将雌性Sprague-Dawley大鼠分为八组（每组三只）：正常对照（NC）±强力霉素组、3周部分BOO（3WPBOO）±强力霉素组、6周PBOO±强力霉素组、3周PBOO后3周解除梗阻（3WOD）±强力霉素组。所有大鼠给予相同的食物和水，饲养在代谢笼中，处于相同的12小时明暗周期。治疗组皮下注射强力霉素15mg/kg/天，每日两次。测量的排尿变量为24小时内的平均排尿量（AVV）和排尿频率（VF）。排尿行为研究完成后，处死大鼠，切除膀胱并称重。
与NC组相比，除3WPBOO-强力霉素组和3WOD-强力霉素组外，所有研究组的AVV均显著增加（P<0.05）。仅3WOD-强力霉素组的VF显著增加（P<0.05）。除3WOD组外，所有研究组在PBOO后膀胱重量均显著增加（P<0.05）。
这些数据表明，MMP抑制可能会影响对BOO或其缓解反应期间的排尿行为。这是首次临床证明干扰膀胱肌壁重塑的主要靶点可能对膀胱功能有直接影响。
