加味当归芍药散对高催乳素血症大鼠环磷酸腺苷和蛋白激酶A及多巴胺受体水平的影响
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摘要
目的探讨加味当归芍药散对高催乳素血症(HPRL)大鼠环磷酸腺苷(cAMP)、蛋白激酶A(PKA)及多巴胺受体水平的影响。方法选取无特定病原体级雌性健康成年未孕SD大鼠96只,完全随机分成空白对照组、阴性对照组、阳性对照组、高浓度组、中浓度组和低浓度组,每组16只。除了空白对照组不予处理,其余5组进行HPRL造模。造模成功后,空白对照组不给药,阴性对照组将0. 9%氯化钠注射液按1 mg/(kg·d)剂量灌胃,阳性对照组将0. 9%氯化钠注射液和甲磺酸溴隐亭片配成悬浊液,按0. 833 mg/(kg·d)剂量灌胃,高、中、低浓度组将加味当归芍药散按60、30、15 g/(kg·d)剂量灌胃。灌胃30 d后,比较各组大鼠下丘脑中多巴胺D1、D2受体和PKA水平及血清中cAMP及催乳素水平。结果与阴性对照组比较,阳性对照组和高、中浓度组D1受体表达水平增加(P <0. 05或P <0. 01);与阳性对照组比较,中、低浓度组D1受体表达水平降低(P <0. 05或P <0. 01)。与阴性对照组比较,其他5组D2受体表达水平均增加(P <0. 05或P <0. 01);与阳性对照组比较,中、低浓度组D2受体表达水平降低(P <0. 05或P <0. 01)。与阴性对照组比较,阳性对照组和高、中、低浓度组PKA表达水平均明显降低(均P <0. 01);与阳性对照组比较,高、中、低浓度组PKA表达水平均降低(P <0. 01或P <0. 05)。阳性对照组与高、中浓度组血清cAMP、催乳素水平均明显低于阴性对照组[(0. 811±0. 782)、(0. 898±0. 745)、(1. 052±0. 427)比(1. 371±0. 002),(236. 2±4. 1)、(242. 0±8. 5)、(260. 2±4. 8) ng/L比(332. 3±9. 5) ng/L](P <0. 05或P <0. 01)。结论加味当归芍药散通过影响cAMP-PKA信号通路中的多巴胺D2受体来调控治疗大鼠HPRL。
Objective To analyze the effect of modified Danggui Shaoyao powders on cyclic adenosine monophosphate( cAMP),protein kinase A( PKA) and dopamine receptor levels in hyperprolactinemia rats.Methods Ninety-six specific-pathogen-free healthy adult female SD rats were randomly divided into blank control group,negative control group,positive control group,high concentration group,medium concentration group and low concentration group,with 16 rats in each group. Except the blank control group,the other 5 groups were made hyperprolactinemia models. After successful modeling,the blank control group had no extra intervention; the negative control group was given intragastric administration of 0. 9% sodium chloride injection at the dose of 1 mg/( kg·d); the positive control group was given intragastric administration of 0. 833 mg/( kg·d) suspension mixed by 0. 9% sodium chloride injection and bromocriptine mesylate tablets; the high,middle and low concentration groups were given intragastric administration of modified Danggui Shaoyao powders at the doses of 60,30,15 g/( kg·d). After 30 days,levels of dopamine D1 and D2 receptors and PKA in hypothalamus,cAMP and prolactin in serum were analyzed. Results Compared with the negative control group,D1 receptor expression level significantly increased in the positive control group and the high and middle concentration groups( P < 0. 05 or P < 0. 01). Compared with the positive control group,D1 receptor expression level significantly decreased in the middle and low concentration groups( P < 0. 05 or P < 0. 01). Compared with the negative control group,D2 receptor expression level significantly increased in the other 5 groups( P < 0. 05 or P < 0. 01). Compared with the positive control group,D2 receptor expression level significantly decreased in the middle and low concentration groups( P < 0. 05 or P < 0. 01). Compared with the negative control group,PKA expression level significantly decreased in the positive control group and the high,middle and low concentration groups( all P < 0. 01).Compared with the positive control group,PKA expression level significantly decreased in the high,middle and low concentration groups( P < 0. 01 or P < 0. 05). Serum levels of cAMP and prolactin in the positive control group and the high and medium concentration groups were significantly lower than those in the negative control group[( 0. 811 ±0. 782),( 0. 898 ± 0. 745),( 1. 052 ± 0. 427) vs( 1. 371 ± 0. 002);( 236. 2 ± 4. 1),( 242. 0 ± 8. 5),( 260. 2 ±4. 8) ng/L vs( 332. 3 ± 9. 5) ng/L]( P < 0. 05 or P < 0. 01). Conclusion Modified Danggui Shaoyao powders can regulate dopamine D2 receptor of cAMP-PKA signaling pathway for treatment of hyperprolactinemia in rats.
Objective To analyze the effect of modified Danggui Shaoyao powders on cyclic adenosine monophosphate( cAMP),protein kinase A( PKA) and dopamine receptor levels in hyperprolactinemia rats.Methods Ninety-six specific-pathogen-free healthy adult female SD rats were randomly divided into blank control group,negative control group,positive control group,high concentration group,medium concentration group and low concentration group,with 16 rats in each group. Except the blank control group,the other 5 groups were made hyperprolactinemia models. After successful modeling,the blank control group had no extra intervention; the negative control group was given intragastric administration of 0. 9% sodium chloride injection at the dose of 1 mg/( kg·d); the positive control group was given intragastric administration of 0. 833 mg/( kg·d) suspension mixed by 0. 9% sodium chloride injection and bromocriptine mesylate tablets; the high,middle and low concentration groups were given intragastric administration of modified Danggui Shaoyao powders at the doses of 60,30,15 g/( kg·d). After 30 days,levels of dopamine D1 and D2 receptors and PKA in hypothalamus,cAMP and prolactin in serum were analyzed. Results Compared with the negative control group,D1 receptor expression level significantly increased in the positive control group and the high and middle concentration groups( P < 0. 05 or P < 0. 01). Compared with the positive control group,D1 receptor expression level significantly decreased in the middle and low concentration groups( P < 0. 05 or P < 0. 01). Compared with the negative control group,D2 receptor expression level significantly increased in the other 5 groups( P < 0. 05 or P < 0. 01). Compared with the positive control group,D2 receptor expression level significantly decreased in the middle and low concentration groups( P < 0. 05 or P < 0. 01). Compared with the negative control group,PKA expression level significantly decreased in the positive control group and the high,middle and low concentration groups( all P < 0. 01).Compared with the positive control group,PKA expression level significantly decreased in the high,middle and low concentration groups( P < 0. 01 or P < 0. 05). Serum levels of cAMP and prolactin in the positive control group and the high and medium concentration groups were significantly lower than those in the negative control group[( 0. 811 ±0. 782),( 0. 898 ± 0. 745),( 1. 052 ± 0. 427) vs( 1. 371 ± 0. 002);( 236. 2 ± 4. 1),( 242. 0 ± 8. 5),( 260. 2 ±4. 8) ng/L vs( 332. 3 ± 9. 5) ng/L]( P < 0. 05 or P < 0. 01). Conclusion Modified Danggui Shaoyao powders can regulate dopamine D2 receptor of cAMP-PKA signaling pathway for treatment of hyperprolactinemia in rats.
引文
[1]林金芳.女性高泌乳素血症诊治的共识、争议及循证研究方向[J].上海医学,2008,31(2):81-82.Lin JF.Consensus,controversies and evidence-based research directions in the diagnosis and treatment of hyperprolactinemia in women[J].Shanghai Medical Journal,2008,31(2):81-82.
[2]洪文惠,方朝晖.高泌乳素血症中西医研究概况[J].中医药临床杂志,2017,29(8):1183-1186.DOI:10.16448/j.cjtcm.2017.0394.Hong WH,Fang CH.Research progress of hyperprolactinemia in traditional Chinese medicine and Western Medicine[J].Clinical Journal of Traditional Chinese Medicine,2017,29(8):1183-1186.DOI:10.16448/j.cjtcm.2017.0394.
[3]Fitzgerald P,Dinan TG.Prolactin and dopamine:what is the connection?A review article[J].J Psychopharmacol,2008,22(2 Suppl):12-19.DOI:10.1177/0269216307087148.
[4]Ben-Jonathan N,Hnasko R.Dopamine as a prolactin(PRL)inhibitor[J].Endocr Rev,2001,22(6):724-763.DOI:10.1210/edrv.22.6.0451.
[5]牟新霞,施艳秋.基于文献分析的高泌乳素血症中医辨治规律研究[J].江苏中医药,2016,48(11):72-74.Mou XX,Shi YQ.Study on TCM syndrome differentiation and treatment of hyperprolactinemia based on literature analysis[J].Jiangsu Journal of Traditional Chinese Medicine,2016,48(11):72-74.
[6]金泽祥,王雄.白芍提取物通过多巴胺D2受体治疗大鼠高泌乳素血症[J].中成药,2016,38(4):741-745.DOI:10.3969/j.issn.1001-1528.2016.04.005.Jin ZX,Wang X.White paeony root aqueous extract treats hyperprolactinemia rats via dopamine D2 receptor[J].Chinese Traditional Patent Medicine,2016,38(4):741-745.DOI:10.3969/j.issn.1001-1528.2016.04.005.
[7]Wang X,Ma L,Zhang EJ,et al.Water extract of fructus hordei germinatus shows antihyperprolactinemia activity via dopamine D2receptor[J].Evid Based Complement Alternat Med,2014,2014:579054.DOI:10.1155/2014/579054.
[8]刘琛.加味当归芍药散治疗高泌乳素血症的临床研究[J].中国中医药现代远程教育,2017,15(12):92-94.DOI:10.3969/j.issn.1672-2779.2017.12.041.Liu C.Clinical research on modified Danggui Shaoyao powder in treating hyperprolactinemia[J].Chinese Medicine Modern Distance Education of China,2017,15(12):92-94.DOI:10.3969/j.issn.1672-2779.2017.12.041.
[9]孙延鸣,欧阳五庆,钱菊汾.环腺苷酸对体外培养的山羊乳腺上皮细胞增殖的影响[J].中国兽医科技,2002,32(2):34-36.Sun YM,Ouyang WQ,Qian JF.Effect of cyclic adenylate on proliferation of goat mammary epithelial cells cultured in vitro[J].Chinese Journal of Veterinary Science and Technology,2002,32(2):34-36.
[2]洪文惠,方朝晖.高泌乳素血症中西医研究概况[J].中医药临床杂志,2017,29(8):1183-1186.DOI:10.16448/j.cjtcm.2017.0394.Hong WH,Fang CH.Research progress of hyperprolactinemia in traditional Chinese medicine and Western Medicine[J].Clinical Journal of Traditional Chinese Medicine,2017,29(8):1183-1186.DOI:10.16448/j.cjtcm.2017.0394.
[3]Fitzgerald P,Dinan TG.Prolactin and dopamine:what is the connection?A review article[J].J Psychopharmacol,2008,22(2 Suppl):12-19.DOI:10.1177/0269216307087148.
[4]Ben-Jonathan N,Hnasko R.Dopamine as a prolactin(PRL)inhibitor[J].Endocr Rev,2001,22(6):724-763.DOI:10.1210/edrv.22.6.0451.
[5]牟新霞,施艳秋.基于文献分析的高泌乳素血症中医辨治规律研究[J].江苏中医药,2016,48(11):72-74.Mou XX,Shi YQ.Study on TCM syndrome differentiation and treatment of hyperprolactinemia based on literature analysis[J].Jiangsu Journal of Traditional Chinese Medicine,2016,48(11):72-74.
[6]金泽祥,王雄.白芍提取物通过多巴胺D2受体治疗大鼠高泌乳素血症[J].中成药,2016,38(4):741-745.DOI:10.3969/j.issn.1001-1528.2016.04.005.Jin ZX,Wang X.White paeony root aqueous extract treats hyperprolactinemia rats via dopamine D2 receptor[J].Chinese Traditional Patent Medicine,2016,38(4):741-745.DOI:10.3969/j.issn.1001-1528.2016.04.005.
[7]Wang X,Ma L,Zhang EJ,et al.Water extract of fructus hordei germinatus shows antihyperprolactinemia activity via dopamine D2receptor[J].Evid Based Complement Alternat Med,2014,2014:579054.DOI:10.1155/2014/579054.
[8]刘琛.加味当归芍药散治疗高泌乳素血症的临床研究[J].中国中医药现代远程教育,2017,15(12):92-94.DOI:10.3969/j.issn.1672-2779.2017.12.041.Liu C.Clinical research on modified Danggui Shaoyao powder in treating hyperprolactinemia[J].Chinese Medicine Modern Distance Education of China,2017,15(12):92-94.DOI:10.3969/j.issn.1672-2779.2017.12.041.
[9]孙延鸣,欧阳五庆,钱菊汾.环腺苷酸对体外培养的山羊乳腺上皮细胞增殖的影响[J].中国兽医科技,2002,32(2):34-36.Sun YM,Ouyang WQ,Qian JF.Effect of cyclic adenylate on proliferation of goat mammary epithelial cells cultured in vitro[J].Chinese Journal of Veterinary Science and Technology,2002,32(2):34-36.