摘要
目的:观察连翘酯苷A对化疗小鼠胃肠动力障碍的影响,并探讨其调节胃肠动力的作用机制。方法:将60只KM小鼠随机分为正常组、模型组、甲氧氯普胺组(5 mg·kg^(-1))及连翘酯苷A低、中、高剂量组(30,60,120 mg·kg^(-1)),每组10只,雌雄各半。各组分别灌胃给药,灌胃容积均为10 mL·kg^(-1),每日1次,连续4 d。灌胃第1天1 h后,除正常组腹腔注射等量生理盐水外,其余各组均腹腔注射顺铂2 mg·kg^(-1),连续4 d。观察连翘酯苷A对模型小鼠胃排空和小肠推进的影响;采用酶联免疫吸附测定(ELISA)检测血清中胃泌素(GAS),生长抑素(SS),胃动素(MTL),血管活性肠肽(VIP)水平,检测胃窦和回肠组织中乙酰胆碱酯酶(AChE)和总一氧化氮合酶(tNOS)的活性;蛋白免疫印迹法(Western blot)检测胃窦和回肠组织AChE和诱导型一氧化氮合酶(iNOS)的蛋白表达水平。结果:与正常组比较,模型组小鼠胃残留率和小肠推进率均显著升高(P<0.01),血清MTL,GAS,SS,VIP含量均明显降低(P<0.05,P<0.01),回肠组织匀浆中AChE活性显著降低(P<0.01),胃窦和回肠组织中tNOS活性均明显升高(P<0.05,P<0.01),胃窦和回肠组织中AChE蛋白表达水平均明显降低(P<0.05),iNOS蛋白表达水平均显著升高(P<0.05);与模型组比较,不同剂量连翘酯苷A可以不同程度地降低小鼠胃残留率和小肠推进率,升高血清MTL,GAS,SS,VIP含量,升高胃窦和回肠组织中AChE活性及蛋白表达水平,降低胃窦和回肠组织中tNOS活性和iNOS蛋白表达水平(P<0.05,P<0.01)。结论:连翘酯苷A对顺铂所致的小鼠胃排空延缓和小肠推进亢进具有显著改善作用,其改善化疗所致胃肠功能障碍的机制与调节胃肠道AChE与NOS活性以及调节胃肠激素水平有关。
Objective: To observe the effect of forsythiaside A on gastrointestinal motility disorder induced by chemotherapy in mice,and explore the mechanism of forsythiaside A regulating gastrointestinal motility. Method: The 60 KM mice were randomly divided into normal group,model group,metoclopramide group(5 mg·kg^(-1))and forsythiaside A low,medium and high-dose groups(30,60,120 mg·kg^(-1)),10 for each group,which include half male and half female. The above dose was given once a day for 4 consecutive days,which the intragastric volume was 10 mL·kg^(-1). One hour after 1 rdday administration,equal volume of saline was intraperitoneally injected to the normal group,2 mg·kg^(-1) cisplatin was intraperitoneally injected to the other groups with daily for 4 consecutive days. Observing the effects of forsythiaside A on gastric emptying and small intestinal propulsion on mice models,serum gastrin(GAS)and somatostatin(SS),motilin(MTL),vasoactive intestinal peptide(VIP)levels were examined by enzyme-linked immunosorbent assay(ELISA). Activities of acetylcholinesterase(AChE)and total nitric oxide synthase(tNOS)in gastric antrum and ileum were detected by ELISA. The expression of AChE and inducible nitric oxide synthase(iNOS)in gastric antrum and ileum were detected by Western blot. Result: Compared with normal group,the gastric retention rate and small intestinal propulsion rate of the model group were significantly increased(P<0.01),serum levels of MTL,GAS,SS and VIP,the AChE activity in the homogenate of ileum in the model group were significantly reduced(P<0.05,P<0.01),while the tNOS activities in gastric antrum and ileum were significantly increased(P<0.05,P<0.01).Protein expression of AChE in gastric antrum and ileum were significantly decreased(P<0.05),and the expression level of iNOS protein was significantly increased in the model group(P<0.05). Compared with model group,different doses of forsythiaside A can reduce the gastric residual rate and small intestinal propulsion rate of mice to varying degrees. Meanwhile forsythiaside A can increase the serum levels of MTL,GAS,SS,and VIP, and the AChE activity and protein expression levels in gastric antrum and ileum tissues were also increased, while tNOS activity and iNOS protein expression were decreased in gastric antrum and ileum(P<0.05,P<0.01). Conclusion: Forsythiaside A can significantly ameliorate the delayed gastric emptying and small intestine hyperfunction induced by cisplatin in mice. Its mechanism to ameliorate gastrointestinal dysfunction caused by chemotherapy is related to the regulation of gastrointestinal AChE and NOS activity in gastric antrum and ileum and the regulation of gastrointestinal hormone levels.
作者
毕娉娉
陈斯琪
张广龙
李雅琦
冼奕宏
张瑞芳
王巧
聂克
BI Ping-ping;CHEN Si-qi;ZHANG Guang-long;LI Ya-qi;XIAN Yi-hong;ZHANG Rui-fang;WANG Qiao;NIE Ke(School of Chinese Materia Medic a,Guangdong Pharmaceutical University,Guangzhou 510006,China)
出处
《中国实验方剂学杂志》
CAS
CSCD
北大核心
2021年第1期105-111,共7页
Chinese Journal of Experimental Traditional Medical Formulae
基金
2019年度广东省重点学科科研项目(2019-GDXK-0011)。
关键词
连翘酯苷A
顺铂
胃肠动力
乙酰胆碱酯酶
胃肠激素
小鼠
forsythiaside A
cisplatin
gastrointestinal motility
acetylcholinesterase
gastrointestinal hormones
mice
作者简介
第一作者:毕娉娉,在读硕士,从事中药药理研究,E-mail:pingping.bi@foxmail.com;通信作者:聂克,教授,博士生导师,从事中药药理研究.Tel:020-39352557,E-mail:nicknk@hotmail.com。
