Hong Sung K, Yang Ji H, Kim Tae B, Kim Soo W, Paick Jae-Seung
Department of Urology, Seoul National University, Seoul, Korea.
BJU Int. 2006 Nov;98(5):1114-7. doi: 10.1111/j.1464-410X.2006.06486.x.
To investigate the effects of ovariectomy and oestrogen replacement on the function and expression of Rho-kinase in rat bladder smooth muscle, as the actual effects of oestrogen deprivation on bladder smooth muscle are unclear.
Female Sprague-Dawley rats were placed into one of three groups: sham-operated, bilateral ovariectomy-only, and bilateral ovariectomy plus oestrogen replacement groups. In the last group, oestrogen was replaced by weekly injection of beta-estradiol 17-cypionate (250 microg/kg subcutaneously for 6 weeks) beginning at 1 week after ovariectomy, whereas the other groups received vehicle-only injections for 6 weeks. After treatment, the bladder was removed for muscle strip studies to evaluate the effects of Y-27632, a specific inhibitor of Rho-kinase, on baseline tension and carbachol-induced tonic contractions. Also, the protein expression of RhoA and Rho-kinase isoenzymes was assessed by Western blot analysis.
Of the three groups, incubation with 10 microm Y-27632 resulted in the largest decrease in baseline tension of strips from the bilateral ovariectomy-only group, but this was not statistically significant (P > 0.05). For carbachol-induced tonic contractions, strips from the bilateral ovariectomy-only group were attenuated the most among the three groups after adding Y-27632 (P < 0.05). However, there were no significant differences in the levels of RhoA and the two Rho-kinase isoenzymes in bladder tissues from the three groups.
Our data show that oestrogen might inhibit the function of Rho-kinase in bladder smooth muscle, while having no significant effect on its expression. This finding might help to explain the greater incidence of urinary tract symptoms suggestive of overactive bladder after the menopause in women.
由于雌激素缺乏对膀胱平滑肌的实际影响尚不清楚，本研究旨在探讨卵巢切除及雌激素替代对大鼠膀胱平滑肌中Rho激酶功能及表达的影响。
将雌性Sprague-Dawley大鼠分为三组：假手术组、单纯双侧卵巢切除组和双侧卵巢切除加雌激素替代组。在最后一组中，从卵巢切除术后1周开始，每周皮下注射17-环戊丙酸雌二醇（250μg/kg，共6周）进行雌激素替代，而其他组仅注射溶剂，持续6周。治疗后，取出膀胱进行肌条研究，以评估Rho激酶特异性抑制剂Y-27632对基线张力和卡巴胆碱诱导的强直性收缩的影响。此外，通过蛋白质印迹分析评估RhoA和Rho激酶同工酶的蛋白表达。
在三组中，用10μmol Y-27632孵育后，单纯双侧卵巢切除组肌条的基线张力下降幅度最大，但差异无统计学意义（P>0.05）。对于卡巴胆碱诱导的强直性收缩，添加Y-27632后，单纯双侧卵巢切除组肌条的收缩减弱最为明显（P<0.05）。然而，三组膀胱组织中RhoA和两种Rho激酶同工酶的水平无显著差异。
我们的数据表明，雌激素可能抑制膀胱平滑肌中Rho激酶的功能，而对其表达无显著影响。这一发现可能有助于解释女性绝经后膀胱过度活动症相关尿路症状发生率较高的原因。
