Kido Hiroko, Yasukawa Hiroshi, Hirota Tsuyoshi, Shindo Akihiro, Naruse Tomohiro
Research Laboratories, Kyoto R&D Center, Maruho Co. Ltd., 93 Awata-cho, Chudoji, Shimogyo-ku, 600-8815, Kyoto, Japan.
Int J Colorectal Dis. 2007 Mar;22(3):271-6. doi: 10.1007/s00384-006-0123-8. Epub 2006 Apr 21.
The present study aimed to clarify the mechanisms of a topical ointment containing an Escherichia coli culture suspension and hydrocortisone (Posterisan forte, BCS+HC) in lowering internal anal pressure in conscious rats.
Internal anal pressure was measured using a water-filled balloon system for consecutive 10-min periods. The changes in pressure were evaluated by the number of peaks above 20 mmH2O between 1 and 8 min of recording.
Topical intra-anal application of BCS+HC ointment (160 mg/kg) significantly decreased the internal anal pressure at 3 h after the application. Thereafter, this effect reached a maximum decrease at 4 h and lasted until 6 h. BCS+HC ointment (40, 80, and 160 mg/kg) lowered the internal anal pressure at 4-5 h in a dose-dependent manner. The maximum decrease ratios of the ointment and corresponding hydrocortisone-free ointment (Posterisan, BCS) were 32.6+/-12.7 and 25.7+/-9.0%, respectively, revealing significant pressure-lowering effects compared with a placebo (P<0.05). In contrast, the same ointment containing hydrocortisone alone and other ointments containing steroids or local anesthetics had no effects.
Treatment with 1 mg/kg NG-nitro-L-arginine methyl ester HCl (L-NAME), a non-selective nitric oxide synthase inhibitor, significantly suppressed the effect of BCS+HC ointment (160 mg/kg) in lowering the internal anal pressure. Furthermore, BCS+HC ointment (160 mg/kg) significantly lowered capsaicin-induced high internal anal pressure compared to a placebo.
These findings suggest that BCS+HC and BCS ointments containing an E. coli culture suspension significantly lowered the internal anal pressure due to endogenous nitric oxide production in conscious rats.
本研究旨在阐明一种含有大肠杆菌培养悬液和氢化可的松的外用软膏(强力保赤安,BCS+HC)降低清醒大鼠肛管内压的机制。
使用充水气球系统连续10分钟测量肛管内压。通过记录1至8分钟内高于20 mmHg₂O的峰值数量来评估压力变化。
经肛门局部应用BCS+HC软膏(160 mg/kg)在用药后3小时显著降低肛管内压。此后,这种效应在4小时达到最大降幅,并持续至6小时。BCS+HC软膏(40、80和160 mg/kg)在4至5小时以剂量依赖方式降低肛管内压。该软膏和相应不含氢化可的松的软膏(保赤安,BCS)的最大降幅分别为32.6±12.7%和25.7±9.0%,与安慰剂相比显示出显著的降压效果(P<0.05)。相比之下,单独含有氢化可的松的相同软膏以及其他含有类固醇或局部麻醉剂的软膏则无此作用。
用1 mg/kg NG-硝基-L-精氨酸甲酯盐酸盐(L-NAME),一种非选择性一氧化氮合酶抑制剂进行治疗,显著抑制了BCS+HC软膏(160 mg/kg)降低肛管内压的作用。此外,与安慰剂相比,BCS+HC软膏(160 mg/kg)显著降低了辣椒素诱导的高肛管内压。
这些发现表明,含有大肠杆菌培养悬液的BCS+HC和BCS软膏可通过内源性一氧化氮生成显著降低清醒大鼠的肛管内压。