文献类型：期刊文献

中文题名：基于EGFR/PI3K/AKT信号通路探讨延胡索乙素对子宫内膜异位症痛经SD大鼠的作用

英文题名：Effects of Tetrahydropalmatine on endometriosis dysmenorrhoea in SD rats based on EGFR/PI3K/AKT signaling pathway

作者：张作良[1];王婉润[1];林祥羽[1];王家兴[1];胡安鑫[1];张志瑞[1];杨亚玲[2];武权生[1]

第一作者：张作良

机构：[1]甘肃中医药大学中医临床学院,甘肃兰州730000;[2]甘肃中医药大学附属医院妇产科,甘肃兰州730030

第一机构：甘肃中医药大学中医临床学院

年份：2025

卷号：41

期号：3

起止页码：381

中文期刊名：中国临床药理学杂志

外文期刊名：The Chinese Journal of Clinical Pharmacology

收录：;北大核心:【北大核心2023】；

基金：国家自然科学基金资助项目(82260949);甘肃省自然科学基金资助项目(23JRRA1199);甘肃省中医药科研基金资助项目(GZKP-2022-22);兰州市科技计划基金资助项目(2021-1-97);甘肃中医药大学附属医院院内课题基金资助项目(gzfy-2021-03)。

语种：中文

中文关键词：延胡索乙素;子宫内膜异位症;痛经;表皮生长因子受体/磷酸肌醇3-激酶/蛋白激酶B信号通路

外文关键词：Tetrahydropalmatine;endometriosis;dysmenorrhoea;epidermal growth factor receptor/phosphatidylinositol 3-kinase/protein kinase B signaling pathway

摘要：目的观察延胡索乙素对子宫内膜异位症痛经SD大鼠表皮生长因子受体(EGFR)/磷酸肌醇3-激酶(PI3K)/蛋白激酶B(AKT)信号通路的影响。方法将60只SPF级雌性SD大鼠用自体移植法复制子宫内膜异位症痛经模型,造模成功后,按体质量随机分为模型组、对照组和低、中、高剂量实验组,每组12只;另取12只正常大鼠作为空白组。空白组及模型组均灌胃给予10 mL·kg^(-1)0.9%NaCl,对照组灌胃给予0.25 mg·kg^(-1)孕三烯酮混悬液。低、中、高剂量实验组分别灌胃给予10、20、40 mg·kg^(-1)延胡索乙素混悬液。6组大鼠每天给药1次,连续给药4周。末次给药后,给予缩宫素2 U诱发宫缩,观察大鼠扭体反应。用酶联免疫吸附试验法测定各组大鼠血清中肿瘤坏死因子-α(TNF-α)、表皮生长因子(EGF)和EGFR含量,用蛋白质印迹法检测异位子宫内膜组织中EGFR、PI3K和AKT蛋白的相对表达水平。结果中、高剂量实验组和对照组、模型组、空白组的扭体次数分别为(9.25±1.42)、(8.33±1.88)、(11.17±2.41)、(28.67±2.15)和0次,扭体反应抑制率分别为67.74%、70.95%、61.05%、0和0,血清TNF-α含量分别为(281.96±13.06)、(278.75±10.39)、(282.12±14.47)、(303.59±9.09)和(274.26±15.33)ng·L^(-1),血清EGF含量分别为(313.82±13.23)、(308.26±10.90)、(311.39±19.52)、(336.04±17.60)和(301.67±27.17)pg·mL^(-1),血清EGFR含量分别为(315.71±7.56)、(311.43±11.04)、(313.75±7.26)、(333.56±14.22)和(307.86±17.94)ng·L^(-1),EGFR蛋白相对表达水平分别为1.60±0.39、1.26±0.30、1.40±0.40、2.08±0.41和1.00±0.22,PI3K蛋白相对表达水平分别为1.60±0.42、1.21±0.18、1.27±0.24、2.01±0.41和1.00±0.19,AKT蛋白相对表达水平分别为1.27±0.18、1.11±0.10、1.27±0.16、1.64±0.28和1.00±0.07。中、高剂量实验组的上述指标与模型组相比,在统计学上差异均有统计学意义(P<0.01,P<0.05)。结论延胡索乙素可能通过干预EGFR/PI3K/AKT信号通路,对子宫内膜异位症痛经起到治疗作用。
Objective To observe the effect of Tetrahydropalmatine on the epidermal growth factor receptor/phosphatidylinositol 3-kinase/protein kinase B(EGFR/PI3K/AKT)signaling pathway in endometriosis dysmenorrhoea SD rats.Methods The endometriosis dysmenorrhoea model was replicated by auto-transplantation in 60 female SD rats of SPF grade.After successful modelling,the rats were randomly divided into model group,control group and experimental-L,-M,-H groups according to body mass,with 12 rats in each group;and another 12 normal rats were taken as the blank group.The blank and model groups were given10 mL·kg^(-1)0.9%NaCl by gavage,and the control group was given 0.25 mg·kg^(-1)progesterone suspension by gavage.The experimental-L,experimental-M,experimental-H groups were given 10,20 and 40 mg·kg^(-1)Tetrahydropalmatine suspension by gavage,respectively.Six groups of rats were administered once daily for 4 weeks.After the last administration,2 U of oxytocin was given to induce contractions,and the rats were observed for torsional responses.The serum levels of tumor necrosis factor-α(TNF-α),epidermal growth factor(EGF),and EGFR were measured by enzyme-linked immunosorbent assay in each group of rats,and the expression levels of EGFR,PI3K and AKT proteins in ectopic endometrial tissues were detected by Western blotting.Results The number of twists in the experimental-M,-H groups and control group,model group,blank group were 9.25±1.42,8.33±1.88,11.17±2.41,28.67±2.15 and 0;the inhibition rates were 67.74%,70.95%,61.05%,0 and 0;serum TNF-αlevels were(281.96±13.06),(278.75±10.39),(282.12±14.47),(303.59±9.09)and(274.26±15.33)ng·L^(-1);serum EGF levels were(313.82±13.23),(308.26±10.90),(311.39±19.52),(336.04±17.60)and(301.67±27.17)g·mL^(-1);serum EGFR levels were(315.71±7.56),(311.43±11.04),(313.75±7.26),(333.56±14.22)and(307.86±17.94)ng·L^(-1);the relative expression levels of EGFR protein were 1.60±0.39,1.26±0.30,1.40±0.40,2.08±0.41 and 1.00±0.22;the relative expression levels of PI3K protein were1.60±0.42,1.21±0.18,1.27±0.24,2.01±0.41 and 1.00±0.19;the relative expression levels of AKT protein were 1.27±0.18,1.11±0.10,1.27±0.16,1.64±0.28 and 1.00±0.07,respectively.Statistically significant differences were found between the above indicators in the experimental-M,-H groups compared to the model group(P<0.01,P<0.05).Conclusion Tetrahydropalmatine may play a therapeutic role in endometriosis dysmenorrhoea by interfering with the EGFR/PI3 K/AKT signaling pathway.