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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
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| 篇名： | 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 |
| TITLE： | Mechanism of Mayuan tongbian zhitong decoction on improving slow-transmission constipation in rats by regulating AMPK/eNOS signaling pathway |
| 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、18mg/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、－4.83kJ/mol，与eNOS的结合能分别为－6.11、－5.40、－5.91kJ/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。 |
| 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 group was decreased significantly （P＜0.05）； colonic structure was disordered ，and a large number of inflammatory cells were seen in submucosa ；the levels of NO and NOS in colon tissue as well as the protein expressions of AMPK ，eNOS，mTOR，Tsc-1，Tsc-2 and 4ebp were increased significantly （P＜0.05）. Compared with model group ，above indexes of Mayuan tongbian zhitong decoction groups （except for NOS in low-dose group ）were reserved significantly （P＜0.05）. In the molecular docking experiment ，the active components with the highest Degree values in C. sativa ，C. aurantium and R. glutinosa were（Z）-3-（4-hydroxy-3-methoxy-phenyl）-N-[2-（4-hydroxyphenyl）ethyl] acrylamide，nobiletin and stigmasterol. The binding energies of AMPK with these three components were －5.15，－4.61 and －4.83 kJ/mol，the binding energies of eNOS with these three components were －6.11，－5.40 and －5.91 kJ/mol. The conformations of these three compounds with AMPK and eNOS were stable and their binding activities were high. CONCLUSIONS Mayuan tongbian zhitong decoction can improve the constipation symptoms and intestinal function in STC model rats ，and its specific mechanism may be related to the inhibition of AMPK/eNOS signaling pathway. |
| 期刊： | 2022年第33卷第13期 |
| 作者： | 谢昌营，余绪超，葛巍，吴成成，肖慧荣，林申奇，刘金连 |
| AUTHORS： | XIE Changying，YU Xuchao，GE Wei，WU Chengcheng，XIAO Huirong，LIN Shenqi，LIU Jinlian |
| 关键字： | 麻元通便止痛汤；慢传输型便秘；AMPK/eNOS信号通路；作用机制 |
| KEYWORDS： | Mayuan tongbian zhitong decoction ；slow-transmission constipation ；AMPK/eNOS signaling pathway ；mechanism |
| 阅读数： | 257 次 |
| 本月下载数： | 3 次 |
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