目的 探讨吴茱萸碱对原发性痛经大鼠的改善作用及其可能的作用机制.方法 将雌性SD大鼠随机分为正常组、模型组、阳性对照组和吴茱萸碱低、中、高剂量组,每组10只.除正常组外,其余组大鼠均构建原发性痛经大鼠模型,吴茱萸碱低、中、高剂量组大鼠分别灌胃10、20、40 mg·kg-1吴茱萸碱,阳性对照组大鼠每天灌胃2.1 g·kg-1痛经宝颗粒,正常组和模型组大鼠灌胃等量的0.9％NaCl.记录各组大鼠扭体次数和扭体潜伏期,以酶联免疫吸附测定(ELISA)法检测血清相关因子表达水平和子宫组织Ca2+含量,以硫代巴比妥酸法、黄嘌呤氧化酶法分别检测血清丙二醛(MDA)和超氧化物歧化酶(SOD)水平,以苏木精-伊红(HE)染色观察子宫病理学变化,以蛋白质印迹法检测子宫组织蛋白表达水平.结果 正常组、模型组、吴茱萸碱低剂量组、吴茱萸碱中剂量组、吴茱萸碱高剂量组和阳性对照组前列腺素F2α(PGF2α)/前列腺素E2(PGE2)值分别为 0.73±0.07、2.35±0.44、1.84±0.18、1.40±0.17、1.04±0.12 和0.97±0.14;Ca2+含量分别为(1.00±0.17)、(2.57±0.33)、(2.01±0.24)、(1.68±0.11)、(1.38±0.16)和(1.78±0.10)nmol·gprot-1;MDA 水平分别为(3.11±0.19)、(5.07±0.19)、(4.54±0.18)、(4.01±0.13)、(3.37±0.25)和(4.25±0.37)nmol·mL-1;前列腺素E受体2(EP2)蛋白水平分别为0.25±0.03、0.75±0.09、0.62±0.06、0.53±0.06、0.32±0.03和 0.72±0.07;Nod样受体蛋白3(NLRP3)蛋白水平分别为0.35±0.04、0.87±0.07、0.71±0.03、0.58±0.04、0.42±0.03 和 0.82±0.05;胱天蛋白酶-1(caspase-1)蛋白水平分别为 0.40±0.06、0.90±0.07、0.73±0.07、0.59±0.06、0.45±0.03和0.86±0.07;以上指标,模型组与正常组比较,吴茱萸碱低、中、高剂量组分别与模型组比较,吴茱萸碱各剂量组之间比较,在统计学上差异均有统计学意义(均P＜0.05).结论 吴茱萸碱可能通过抑制EP2/NLRP3/caspase-1通路,改善大鼠原发性痛经.
Objective To investigate the ameliorative effect of Evodiamine on primary dysmenorrhea in rats and its possible mechanism.Methods Female SD rats were randomly divided into normal group,model group,evodiamine low dose group,evodiamine medium dose group,evodiamine high dose group and positive control group,with 10 rats in each group.The primary dysmenorrhea model was established in all the other groups except the normal group.The rats in evodiamine low,medium and high dose groups were intragaically given 10,20 and 40 mg·kg-1 evodipine,respectively.Rats in positive control group were given 2.1 g·kg-1 Tongjingbao granules every day,and rats in normal group and model group were given the same amount of 0.9％NaCl.The times and latency of twisting were recorded in each group.The expression level of serum related factors and the content of Ca2+in uterine tissue were detected by enzyme-linked immunosorbent assay(ELISA).Serum malondialdehyde(MDA)and superoxide dismutase(SOD)levels were detected by thiobarbituric acid method and xanthine oxidase method.Hematoxylin-eosin(HE)staining was used to observe the pathological changes of uterus in each group.The expression of uterine tissue protein was detected by Western blot.Results The prostaglandin F2α(PGF2α)/prostaglandin E2(PGE2)values of normal group,model group,evodiamine low dose group,evodiamine medium dose group,evodiamine high dose group and positive control group were 0.73±0.07,2.35±0.44,1.84±0.18,1.40±0.17,1.04±0.12,and 0.97±0.14;Ca2+content were(1.00±0.17),(2.57±0.33),(2.01±0.24),(1.68±0.11),(1.38±0.16)and(1.78±0.10)nmol·gprot-1;MDA levels were(3.11±0.19),(5.07±0.19),(4.54±0.18),(4.01±0.13),(3.37±0.25)and(4.25±0.37)nmol·mL-1;prostaglandin E receptor 2(EP2)protein levels were 0.25±0.03,0.75±0.09,0.62±0.06,0.53±0.06,0.32±0.03,0.72±0.07,respectively;the Nod-like receptor protein 3(NLPP3)protein levels were 0.35±0.04,0.87±0.07,0.71±0.03,0.58±0.04,0.42±0.03 and 0.82±0.05;the protein levels of cysteine aspartic acid specific protease-1(caspase-1)were 0.40±0.06,0.90±0.07,0.73±0.07,0.59±0.06,0.45±0.03 and 0.86±0.07,respectively.The above indicators,comparison between model group and normal group,comparison between evodiamine low,medium,high dose groups and model group,comparison between different dosage groups of evodiamine,the differences were all statistically significant(all P＜0.05).Conclusion Evodiamine may improve primary dysmenorrhea in rats by inhibiting EP2/NLRP3/caspase-1 pathway.
姜美佳;高希焕;范楷;薛萍
青岛市中医医院、市海慈医院中医妇科,山东青岛 266033
中医学
吴茱萸碱;原发性痛经;前列腺素F2α;6-酮前列腺素F1α;前列腺素E受体2/Nod样受体蛋白3通路
evodiamine;primary dysmenorrhea;prostaglandin F2α;6-keto prostaglandin F1-α;prostaglandin E receptor 2/Nod-like receptor protein 3 pathway
《中国临床药理学杂志》 2024 (005)
708-712 / 5
10.13699/j.cnki.1001-6821.2024.05.016
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