Department of Gastroenterology, 175 Hospital of PLA, Affiliated Southeast Hospital of Xiamen University, Zhangzhou 363000, Fujian Province, China.
World J Gastroenterol. 2013 Jul 28;19(28):4582-9. doi: 10.3748/wjg.v19.i28.4582.
To assess the protective effect of berberine administration and the role of nitric oxide (NO) in visceral hypersensitivity.
Fifty male Sprague-Dawley rats were randomly assigned to five groups. An inflammatory bowel disease model was induced in rats by intracolonic instillation of 1 mL 4% acetic acid at 8 cm proximal to the anus for 30 s and restraint stress. After subsidence of inflammation on day 7 of the experiment, the rats were subjected to rectal distension, performed by a balloon (6-Fr, 2 mm external diameter, disposable silicon balloon-urethral catheter for pediatric use) which was rapidly inflated with increasing volumes of prewarmed (37 °C) water (0.1, 0.2, 0.3, 0.4, 0.6, 0.8 and 1 mL) for 30 s at four-minute intervals, and then the abdominal withdrawal reflex (AWR) and the level of fecal output were measured, respectively. AWR scores either 0, 1, 2, 3 or 4 were obtained by blinded observers. Rats had been pretreated with berberine or aminoguanidine (NO synthetase inhibitor) or berberine + aminoguanidine before measurement.
The rats in the placebo group showed a hypersensitive response to rectal distension (2.69 ± 0.08 vs 1.52 ± 0.08, P = 0.000) and defecated more frequently than those in the control group (5.0 ± 0.16 vs 0.44 ± 0.16, P = 0.000). Comparing the berberine with placebo group, the AWR scores were reduced for all distension volumes and were significant at 0.2-1 mL (1.90 ± 0.08 vs 2.69 ± 0.08, P = 0.000), while the numbers of hard pellets, soft pellets, formless stools, and total fecal output in the placebo group were significantly larger than in the berberine group (5.0 ± 0.16 vs 2.56 ± 0.16, P = 0.000). Administration of aminoguanidine or berberine + aminoguanidine before VH score measurement reversed the antinociceptive effect of berberine (2.52 ± 0.08 vs 1.90 ± 0.08, P = 0.000; 2.50 ± 0.08 vs 1.90 ± 0.08, P = 0.000). The numbers of hard pellets, soft pellets, formless stool, and total of fecal output in aminoguanidine group were significantly larger than the corresponding values in control group, berberine group, and berberine + aminoguanidine group (4.81 ± 0.16 vs 0.44 ± 0.16, P = 0.000; 4.81 ± 0.16 vs 2.56 ± 0.16, P = 0.000; 4.81 ± 0.16 vs 3.75 ± 0.16, P = 0.000). The berberine and berberine + aminoguanidine groups showed reduced defecation, but aminoguanidine alone did not reduce defecation (2.56 ± 0.16 vs 4.81 ± 0.16, P = 0.000; 3.75 ± 0.16 vs 4.81 ± 0.16, P = 0.000).
Berberine had an antinociceptive effect on visceral hypersensitivity, and NO might play a role in this effect.
评估小檗碱给药对内脏高敏性的保护作用及一氧化氮（NO）的作用。
将 50 只雄性 Sprague-Dawley 大鼠随机分为 5 组。通过向距肛门 8cm 近端的结肠内注入 1ml4%醋酸 30s 并限制应激，诱导大鼠炎症性肠病模型。在实验第 7 天炎症消退后，通过快速向预加热（37°C）的水中充气（0.1、0.2、0.3、0.4、0.6、0.8 和 1ml，持续 30s），对大鼠进行直肠扩张，然后分别测量腹外反射（AWR）和粪便排出量。通过盲法观察者获得 AWR 评分 0、1、2、3 或 4。在测量前，大鼠先用小檗碱或氨基胍（NO 合酶抑制剂）或小檗碱+氨基胍预处理。
与对照组相比，安慰剂组大鼠对直肠扩张的反应更为敏感（2.69±0.08 比 1.52±0.08，P=0.000），且排便次数也更多（5.0±0.16 比 0.44±0.16，P=0.000）。与安慰剂组相比，小檗碱组所有扩张体积的 AWR 评分均降低，且在 0.2-1ml 时差异具有统计学意义（1.90±0.08 比 2.69±0.08，P=0.000），而安慰剂组的硬便粒数、软便粒数、不成形粪便数和总粪便排出量均明显多于小檗碱组（5.0±0.16 比 2.56±0.16，P=0.000）。在 VH 评分测量前给予氨基胍或小檗碱+氨基胍，逆转了小檗碱的镇痛作用（2.52±0.08 比 1.90±0.08，P=0.000；2.50±0.08 比 1.90±0.08，P=0.000）。氨基胍组的硬便粒数、软便粒数、不成形粪便数和总粪便排出量均明显多于对照组、小檗碱组和小檗碱+氨基胍组（4.81±0.16 比 0.44±0.16，P=0.000；4.81±0.16 比 2.56±0.16，P=0.000；4.81±0.16 比 3.75±0.16，P=0.000）。小檗碱和小檗碱+氨基胍组排便减少，但氨基胍单独使用并未减少排便（2.56±0.16 比 4.81±0.16，P=0.000；3.75±0.16 比 4.81±0.16，P=0.000）。
小檗碱对内脏高敏性有镇痛作用，NO 可能在此作用中发挥作用。
