Effect of granulae Li Wei on gastrointestinal activity

Jing Wang ,Jia Yu Hou(Department of Pharmacology,Beijing University of Traditional Chinese medicine,Beijing 100029,China)

Abstract：AIM to observe the prokinetic effects of granulae Li Wei on experimental animals.METHODS The prokinetic effects of grenulae Li Wei on semisolid meals gastric emptying were evaluated. Mice were given charcoal powder orally to determine theeffects of granulae Li Wei on small intestinal promotion of charcoal powder. Dopamine given intraperitoneally coulddelay gastric emptying and induce retrograde power contractions with enterogastric reflux. Gastric motility was measured in conscious rats using a miniature balloon positioned in the glandular part of the stomach. The balloun was connected to a pressure transducer and polygraph.RESULTS Granulae Li Wei observably inhibited gastric emptying rate of oataplasma feedetuff from 61.4% ±12.9% to 44.7% ±20.2% at 5 g/kg and to 43.8%± 13.9%at 10g/kg. Granulae Li Wei given orally at dose of 10 g/kg once and continuously for seven days both couldremarkably increase small intestinal promotion of charcoal powder,the promotion rate was increased from41.0%±5.0% to 45.0% ± 5.3% and to 45.4%±5.9% respectively.Granulae Li Wei given duedenally at dose of 10 g/kg markedly reduced the refluxing volume of phenol red from 0.37g/L± 0.07g/L to 0.28g/L±0.07g/L Granulae Li Wei also markedly inhibited the delay of gastric emptying induced by dopomine. Gastric emptying rates were increased from 18.66%± 5.63% to 9.6% ± 5.2% at 2.5 g/kg to12.8%±6.9% at 5g/kg and to 6.6% ±3.6% at 10g/kg. Intraduodenal administration of granules Li Wei at 2.5 g/kg and 5g/kg significantly increased the intragastric pressure. The increases in frequency, mean amplitude and the maximal amplitude on gastric muscle contractions could be seen.CONCLUSION granulae Li Wei could influence the gastric contractile activity. It was suggested that granulae Li Wei could harmonize the contactions of stomach and duodenum.

Keywords：granulae li Wei;gastrointestinal activity; gastric emptying; stomach diseases/drug therapy

引言力胃颗粒由百合，乌药，枳实及虎杖四味中药组成，主治胃气失和，胃阴不足兼有血瘀者．我们观察了力胃颗粒对胃肠动力的影响，并对其作用机制进行探讨，以期为其临床应用提供实验依据。1材料和方法1．1材料Wistar大鼠，雌雄兼用，体质量180g～250g中国医学科学院实验动物研究所繁育场提供．昆明种小鼠，，体质量18g～22g，力胃颗粒由北京中医药大学中药学院制剂教研室提供．1g药粉相当于5g生药，使用时以常水配制，所用四个剂量， 2.5g／kg，5g／kg，10g／kg及20g／kg，分别相当于临床人用剂量lg生药／kg的2．5，5，10及20倍；气滞胃痛冲剂，辽宁本溪第三制药厂，研究采用剂量5g／kg，相当于临床人用剂量的10倍；西沙比利(普瑞博思)，杨森制药有限公司；硫酸阿托品注射液，无锡市第七制药厂；戊巴比妥钠，佛山市化工实验厂；苯酚红，北京化工厂；盐酸多巴胺，瑞士Fluka．其他试剂为进口或国产分析纯试剂．电生理数据处理系统Maclab／400(澳大利亚Adl)，722型分光光度计(上海第三分析仪器厂)．1．2方法1．2．1小鼠饲料糊胃排空小鼠禁食24h后随机分组；设空白对照组；阿托品0．5mg／kg组；新斯的明0．08mg／kg组；力胃颗粒5g／kg组及力胃颗粒10g／kg组，参考吴春福etal[1]的方法：每只灌胃糊状饲料0．6mL，15min后拉断颈椎处死，结扎胃贲门及幽门，立即取胃，在电子天平上称全胃质量，然后剪开胃，洗掉胃内容物，将空胃在滤纸上轻拭，蘸去多余水分，再称质量．胃排空率(％)＝[食料质量-(全胃质量-空胃质量)]÷食料质量x100％。1．2．2小鼠炭末肠推进没空白对照组；力胃颗粒10g／kg一次给药组，灌胃给药后3h灌胃炭末；力胃颗粒10g／kg连续7d给药组，末次灌胃给药后1．5h灌胃炭末；气滞胃痛冲剂5g／kg连续7d给药组，末次灌胃绐药后1.5h灌胃炭末；新斯的明0．08mg／kg组，ip新斯的明15min后灌胃炭末．小鼠禁食24h，灌胃50g／L炭末混悬液，10min后脱断颈椎处死，开腹，分离自幽门至回盲部全部小肠，测量小肠全长及炭末头端至幽门距离，计算炭末推进率(％)=炭末头端至幽门距离÷小肠全长×100％[2]。1．2．3盐酸多巴胺致小鼠肠胃反流及胃排空延迟①力胃颗粒对盐酸多巴胺致小鼠肠胃反流的影响．设空白对照组；模型对照组；力胃颗粒10g／kg组；力胃颗粒5g／kg组；气滞胃痛冲剂5g／kg组；西沙比利0．5mg／kg组。空白对照组为乙醚麻醉后十二指肠注射常水1h后灌胃酚红糊，20min后处死；模型对照组为十二指肠注射常水1h后灌胃酚红糊，20min后腹腔注射DA0.2mg／kg，5min后处死；其余各组均为乙醚麻醉后十二指肠药1h后灌胃酚红糊，20min后腹腔注射DA0．2mg／kg，5min后处死．小鼠禁食24h，每只灌胃0．5g／L酚红糊0.25mL，20min后拉断颈椎处死，立即取胃，置于40mL0．1mol／LNaOH溶液中，剪碎，混匀静置，60min后取上清液5mL，加入200g／L三氯醋酸1mL，离心10min(1400r／min)后取上清液lmL，加入0．5mol／LNaOH溶液1mL显色，置722型分光光度计56nm处比色，记录吸光度A．零点对照组为灌胃0．5g／L酚红糊0．25mL后立即处死取胃，测吸光度A．制作酚红标准曲线：C=0．323+4．609A．残留率(％)=各组A÷零点对照组A×100％．肠胃反流公式为：肠胃反流量(g／L)=各组胃内残存酚红浓度-空白对照组胃内残存酚红浓度．②力胃颗粒对盐酸多巴胺致小鼠胃排空延迟的影响．设空白对照组；模型对照组；力胃颗粒2，5g／kg组；力胃颗粒5g／kg组；力胃颗粒10g／kg组；气滞胃痛冲剂2．5g／kg组；西沙比利5mg／kg组．空白对照组为灌胃常水1h后灌胃酚红糊，25min后处死；模型对照组为灌胃常水1h后灌胃酚红糊，15min后ipDA0．2mg／kg，10min后处死；其余各组均为连续4d给药，末次绐药后1h灌胃酚红糊，15min后ipDA，10min后处死．小鼠禁食24h，每只灌胃0．5g／L酚红糊0．25mL，25min后拉断颈椎处死，立即取胃，置于40mL0．1mol／L．NaOH溶液中，剪碎．混匀静置，60min后取上清液5mL，加入200g／L三氯醋酸1mL，离心10min(1400r／min)后取上清液1mL，加入0．5mol／LNaOH溶液1mL显色，置722型分光光度计560min处比色．记录吸光度A．零点对照组为灌胃0．05％酚红糊0．25mL后立即处死取胃，测吸光度A，制作酚红标准曲线：C=0．323-4.609A，残留率(％)=各组A÷零点对照组A×l00％．1．2．4清醒大鼠胃内压力设空白对照组；力胃颗粒2．5g／kg组；力胃颗粒5g／kg组；气滞胃痛冲剂5g／kg组；西沙比利2．5mg／kg组；阿托品1mg／kg组，各组均十二指肠给药，0．5mL／kg．大鼠禁食12h，戊巴比妥钠溶液(15g／L，35mg／kg，ip)麻醉下开腹，暴露出胃及十二指肠，在胃体部前壁上部，靠胃大弯处开一小孔，埋入水囊(最大容积0．8mL的乳胶小球，硅橡胶管长12cm，Di1.5mm，Do2.0mm)，结扎固定，十二指肠同时埋人插管(硅橡胶管长10cm，Di0．8mm，Do1．0mm)，关腹，将两管自耳后皮下引出体外．术后恢复12h，进行胃内压描记，将大鼠放人鼠盒内保持正常卧姿，将水囊硅