Page 87 - 《中国药房》2022年13期

麻元通便止痛汤调控 AMPK/eNOS 信号通路改善大鼠慢传输型

便秘的作用机制 Δ

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谢昌营 ，余绪超 ，葛 巍 ，吴成成 ，肖慧荣 ，林申奇 ，刘金连（1.江西中医药大学附属医院肛肠科，南昌
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330006；2.江西中医药大学研究生院，南昌 330006）
中图分类号 R965 文献标志码 A 文章编号 1001-0408（2022）13-1617-07
DOI 10.6039/j.issn.1001-0408.2022.13.14
摘 要 目的 研究麻元通便止痛汤调控AMP活化蛋白激酶（AMPK）/内皮型一氧化氮合酶（eNOS）信号通路改善大鼠慢传输型
便秘（STC）的作用机制。方法 将大鼠随机分为空白组、模型组和麻元通便止痛汤低、中、高剂量组（6、12、18 mg/kg），每组10只。
除空白组外，其余各组大鼠灌胃复方地芬诺酯混悬液复制STC模型。造模成功后，空白组和模型组大鼠灌胃生理盐水，麻元通便
止痛汤各剂量组大鼠灌胃相应药物，每天1次，连续2周。观察大鼠治疗前后的粪便数量及含水率；计算大鼠的炭末推进率；观察
大鼠结肠组织的病理学变化；检测大鼠结肠组织中一氧化氮（NO）、一氧化氮合酶（NOS）水平及AMPK、eNOS、哺乳动物雷帕霉素
靶蛋白（mTOR）、结节性硬化复合物1（Tsc-1）、Tsc-2、真核启动因子4E结合蛋白（4ebp）的表达水平；筛选麻元通便止痛汤君药火麻
仁、枳壳、生地的活性成分，选择Degree值最高的活性成分与AMPK、eNOS进行分子对接，以验证相互作用。结果 与治疗前比较，
麻元通便止痛汤各剂量组大鼠粪便数量及含水率均显著增加（P＜0.05）。与空白组比较，模型组大鼠炭末推进率显著降低（P＜
0.05）；结肠组织结构紊乱，黏膜下层见大量炎症细胞浸润；结肠组织中 NO、NOS 水平和 AMPK、eNOS、mTOR、Tsc-1、Tsc-2、4ebp
蛋白表达水平均显著升高（P＜0.05）。与模型组比较，麻元通便止痛汤各剂量组上述指标（低剂量组NOS除外）均显著逆转（P＜
0.05）。分子对接结果显示，火麻仁、枳壳、生地中 Degree 值最高的活性成分分别为（Z）-3-（4-hydroxy-3-methoxy- phenyl）-N-[2-
（4-hydroxyphenyl）ethyl]acrylamide、nobiletin、stigmasterol，这 3 种成分与 AMPK 的结合能分别为－5.15、－4.61、－4.83 kJ/mol，与
eNOS的结合能分别为－6.11、－5.40、－5.91 kJ/mol，且结合构象稳定、结合活性较高。结论 麻元通便止痛汤可改善STC模型大
鼠的便秘症状和肠道功能，其作用机制可能与抑制AMPK/eNOS信号通路有关。
关键词 麻元通便止痛汤；慢传输型便秘；AMPK/eNOS信号通路；作用机制

Mechanism of Mayuan tongbian zhitong decoction on improving slow-transmission constipation in rats by
regulating AMPK/eNOS signaling pathway
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XIE Changying ，YU Xuchao ，GE Wei ，WU Chengcheng ，XIAO Huirong ，LIN Shenqi ，LIU Jinlian（1. Dept. of
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Proctology，the Affiliated Hospital of Jiangxi University of Chinese Medicine，Nanchang 330006，China；
2. Graduate School，Jiangxi University of Chinese Medicine，Nanchang 330006，China）
ABSTRACT OBJECTIVE To investigate the mechanism of Mayuan tongbian zhitong decoction on improving slow-transmission
constipation（STC）in rats by regulating AMP activated protein kinase（AMPK）/endothelial nitric oxide synthase（eNOS）signaling
pathway. METHODS The rats were randomly divided into blank group，model group，Mayuan tongbian zhitong decoction
low-dose，medium-dose and high-dose groups（6，12，18 mg/kg），with 10 rats in each group. Except for blank group，other
groups were given Compound diphenoxylate suspension to induce STC model. After modeling，blank group and model group were
given normal saline intragastrically，and Mayuan tongbian zhitong decoction groups were given relevant medicine intragastrically，
once a day，for consecutive 2 weeks. The number of feces and water content of feces in each group were observed before and after
treatment；the carbon powder propulsion rate of rats in each group was calculated；the pathological structure of colon in each group
was observed；the levels of nitric oxide （NO） and nitric oxide synthase （NOS） in colon tissues of rats in each group were
detected；the expressions of AMPK，eNOS，mammalian target of rapamycin（mTOR），tuberous sclerosis complex 1（Tsc-1），
Tsc-2 and eukaryotic promoter 4E binding protein（4ebp）were also detected. The active ingredients of Cannabis sativa，Citrus
aurantium and Rehmannia glutinosa were screened from Mayuan tongbian zhitong decoction. The active ingredients with high
Degree value were docked with AMPK and eNOS，to verify the interaction. RESULTS Compared with before treatment，the
number and water content of feces were increased significantly in Mayuan tongbian zhitong decoction groups（P＜0.05）. Compared
with blank group，carbon powder propulsion rate of model
Δ 基金项目 江西省中医药管理局科技计划项目（No.2021Z005）
group was decreased significantly （P＜0.05） ； colonic
＊第一作者 副主任中医师。研究方向：肛肠疾病临床与实验研
究。电话：0791-86362902。E-mail：xiechangying8@163.com structure was disordered，and a large number of inflammatory
# 通信作者 主任中医师。研究方向：肛肠疾病临床与实验研究。 cells were seen in submucosa；the levels of NO and NOS in
电话：0791-86362902。E-mail：jxszyygck@126.com colon tissue as well as the protein expressions of AMPK，

中国药房 2022年第33卷第13期 China Pharmacy 2022 Vol. 33 No. 13 ·1617 ·