Department of Lower Urinary Tract Medicine, Shinshu University School of Medicine, Matsumoto, Japan.
Neurourol Urodyn. 2013 Jun;32(5):486-92. doi: 10.1002/nau.22335. Epub 2012 Dec 31.
We determined if THC-002, a galenical produced from Ba-Wei-Die-Huang-Wan, could increase skin temperature and inhibit detrusor overactivity induced by sudden whole body cooling. Further, we determined if THC-002 could decrease expression of transient receptor potential melastatin 8 (TRPM8) channels associated with the cold responses.
Hind leg skin temperature of female 10-week-old Sprague-Dawley rats was measured by thermal imaging. Experimental rats (n = 12) were given oral 100 mg/kg THC-002 daily for one week, and controls (n = 12) were similarly treated with THC-002-free solution. Afterwards, thermal imaging and cystometric investigations of the freely moving conscious rats were performed at room temperature (RT, 27 ± 2°C) for 20 min. The rats were then transferred to a low temperature (LT, 4 ± 2°C) environment during which thermal imaging and cystometric measurements were taken at 5, 10, 20, 30, and 40 min. Afterward, the skin tissues were harvested to estimate expression levels of TRPM8 channels by immunohistochemistry and real-time reverse-transcription polymerase chain reaction.
The RT skin temperature of THC-002-treated rats was significantly higher than controls. During the first 20 min under LT, the control rats exhibited cold stress-induced detrusor overactivity such as decreased voiding interval and bladder capacity. THC-002 partially inhibited the detrusor overactivity patterns. During the second 20 min, skin temperature was relatively stable, and the detrusor overactivity of both groups slowly disappeared. THC-002 significantly reduced expression of TRPM8 channel protein and mRNA.
THC-002 inhibited cold stress-induced detrusor overactivity resulting from decreasing skin temperature. Therefore, THC-002 might provide resistance to cold stress-exacerbated lower urinary tract symptoms.
我们旨在研究由八位地黄丸制成的药物 THC-002 是否可以提高皮肤温度并抑制因全身突然降温引起的逼尿肌过度活动。此外，我们还研究了 THC-002 是否可以降低与冷反应相关的瞬时受体电位 melastatin 8（TRPM8）通道的表达。
通过热成像技术测量 10 周龄雌性 Sprague-Dawley 大鼠后腿皮肤温度。实验大鼠（n=12）每日口服给予 100mg/kg THC-002，持续一周，对照组（n=12）同样给予不含 THC-002 的溶液。然后，在室温（27±2°C）下对自由活动的清醒大鼠进行热成像和膀胱测压检查 20 分钟。然后，将大鼠转移到低温（4±2°C）环境中，在 5、10、20、30 和 40 分钟时进行热成像和膀胱测压测量。之后，采集皮肤组织，通过免疫组织化学和实时逆转录聚合酶链反应估计 TRPM8 通道的表达水平。
经 THC-002 治疗的大鼠的 RT 皮肤温度明显高于对照组。在 LT 下的前 20 分钟内，对照组大鼠表现出逼尿肌过度活动，如排尿间隔和膀胱容量减少等冷应激反应。THC-002 部分抑制了逼尿肌过度活动模式。在第二 20 分钟，皮肤温度相对稳定，两组的逼尿肌过度活动均缓慢消失。THC-002 显著降低了 TRPM8 通道蛋白和 mRNA 的表达。
THC-002 通过降低皮肤温度抑制冷应激引起的逼尿肌过度活动。因此，THC-002 可能为缓解冷应激加重的下尿路症状提供了一种治疗选择。
