[1]汪沙 段华** 沈雪.大麻素受体在子宫腺肌病在位内膜中的表达[J].中国微创外科杂志,2021,01(9):817-821.
 Wang Sha,Duan Hua,Shen Xue..Expression of Cannabinoid Receptors in the Eutopic Endometrium in Patients With Adenomyosis[J].Chinese Journal of Minimally Invasive Surgery,2021,01(9):817-821.
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大麻素受体在子宫腺肌病在位内膜中的表达()
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《中国微创外科杂志》[ISSN:1009-6604/CN:11-4526/R]

卷:
01
期数:
2021年9期
页码:
817-821
栏目:
临床研究
出版日期:
2021-09-25

文章信息/Info

Title:
Expression of Cannabinoid Receptors in the Eutopic Endometrium in Patients With Adenomyosis
作者:
汪沙 段华** 沈雪
(首都医科大学附属北京妇产医院妇科微创中心,北京100006)
Author(s):
Wang Sha Duan Hua Shen Xue.
Department of Minimally Invasive Gynecology, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing 100006, China
关键词:
子宫腺肌病大麻素受体CB1CB2子宫内膜
Keywords:
AdenomyosisCannabinoid receptorCB1CB2Endometrium
文献标志码:
A
摘要:
目的研究大麻素受体CB1和CB2在子宫腺肌病患者在位内膜及非腺肌病患者子宫内膜组织中表达的差异。方法选择2017年7月~2018年12月因弥漫型子宫腺肌病行全子宫切除术的45例为腺肌病组(增殖期23例,分泌期22例),同期因宫颈疾病切除子宫的34例非子宫腺肌病患者(宫颈上皮内瘤变Ⅲ级16例,宫颈癌ⅠA期18例)作为对照组(增殖期22例,分泌期12例),通过免疫组化二步法和实时荧光定量PCR技术检测2组子宫内膜CB1、CB2蛋白及mRNA的表达水平。结果①CB1蛋白在腺肌病组增殖期、分泌期在位内膜中表达量均低于对照组(均P=0.000)。腺肌病组CB1蛋白在增殖期与分泌期的表达差异无统计学意义(P=0.101),而对照组增殖期低于分泌期(P=0.009)。②CB2蛋白在腺肌病组增殖期、分泌期在位内膜中表达量均低于对照组(P=0.011、0.000)。2组CB2蛋白的表达均在增殖期低于分泌期(均P=0000)。③CB1 mRNA在腺肌病组增殖期、分泌期在位内膜中的表达量均低于对照组(均P=0.000)。腺肌病组CB1 mRNA在增殖期与分泌期的表达差异无统计学意义(P=0.238),而对照组增殖期低于分泌期(P=0.000)。④CB2 mRNA在腺肌病组增殖期、分泌期在位内膜中的表达量均低于对照组(均P=0.000)。2组CB2 mRNA的表达均在增殖期低于分泌期(均P=0.000)。 结论腺肌病子宫在位内膜中大麻素受体CB1和CB2的表达均下调且CB1的表达失去周期性变化,提示大麻素受体可能参与腺肌病的发生发展。
Abstract:
ObjectiveTo observe the differences of expression of cannabinoid receptors CB1 and CB2 in endometrial samples derived from adenomyosis patients and nonadenomyosis patients.MethodsFrom July 2017 to December 2018, 45 cases of diffuse adenomyosis undergoing hysterectomy were enrolled as the adenomyosis group (23 cases in the proliferative phase and 22 cases in the secretory phase).Another 34 cases of nonadenomyosis (16 cases of cervical intraepithelial neoplasia grade Ⅲ and 18 cases of cervical carcinoma stage ⅠA) in the same period were enrolled as the control group (22 cases in the proliferative phase and 12 cases in the secretory phase). The expression levels of protein and mRNA of CB1 and CB2 in the endometrium of the two groups were detected by immunohistochemistry and realtime PCR.Results①The expression levels of CB1 protein in the eutopic endometrium during the proliferation and secretory phases of the adenomyosis group were lower than those of the control group (both P=0.000). The expression of CB1 protein in the endometrium of the adenomyosis group was not significantly different between proliferation and secretion phase (P=0.101). In the control group, the expression of CB1 protein in the endometrium during the proliferation phase was lower than during the secretion phase (P=0.009). ②The expression levels of CB2 protein in the eutopic endometrium during the proliferation and secretory phases of the adenomyosis group were lower than those of the control group (P=0.011 and 0.000). The expression levels of CB2 protein in both groups were significantly lower in the proliferation phase of endomtrium than in the secretory phase (both P=0.000). ③The expression levels of CB1 mRNA in the eutopic endometrium during the proliferation and secretory phases of the adenomyosis group were lower than those of the control group (both P=0.000). The expression of CB1 mRNA in the adenomyosis group was not significantly different between the proliferation and secretory phases (P=0.238), while in the control group, that during the proliferation phase was lower than the secretory phase (P=0.000). ④The expression levels of CB2 mRNA in the proliferation and secretory phases endometrium of the adenomyosis group were lower than those of the control group (both P=0000). The expression levels of CB2 mRNA in both groups were lower in the proliferative phase than in the secretory phase (both P=0.000).ConclusionThe expressions of CB1 and CB2 decrease in the eutopic endometrium and the CB1 loses its cyclic variation in the eutopic endometrium in adenomyosispatients, suggesting that cannabinoid receptors may participate in the pathogenesis of adenomyosis.

参考文献/References:

[1]董千靖,段华,郑德璇,等.子宫腺肌病患者子宫肌层纤维化程度与痛经的相关性.中华妇产科杂志,2018,53(10):689-693.
[2]汪沙,段华,张颖,等.17β-雌二醇对子宫腺肌病患者子宫内膜-肌层交界区平滑肌细胞钙通路调节的研究.中华妇产科杂志,2015,48(5):876-878.
[3]Balsevich G,Petrie GN,Hill MN.Endocannabinoids:effectors of glucocorticoid signaling.Front Neuroendocrinol,2017,47:86-108.
[4]Lu HC,Mackie K.An introduction to the endogenous cannabinoid system.Biol Psychiatry,2016,79(7):516-525.
[5]Han H,Liang X,Wang J,et al.Cannabinoid receptor 1 contributes to sprouted innervation in endometrial ectopic growth through mitogenactivated protein kinase activation.Brain Res,2017,1663:132-140.
[6]Sanchez AM,Vigano P,Mugione A,et al.The molecular connections between the cannabinoid system and endometriosis.Mol Hum Reprod,2012,18(12):563-571.
[7]Navarrete C,GarciaMartin A,DeMesa J,et al. Cannabinoids in metabolic syndrome and cardiac fibrosis.Curr Hypertens Rep,2020,22(12):98.
[8]FraguasSánchez AI,MartínSabroso C,TorresSuárez AI.Insights into the effects of the endocannabinoid system in cancer:a review. Br J Pharmacol,2018,175(13):2566-2580.
[9]Schmittgen TD,Livak KJ.Analyzing realtime PCR data by the comparative CT method.Nat Protoc,2008,3(6): 1101-1108.
[10]Resuehr D,Glore DR,Taylor HS,et al.Progesteronedependent regulation of endometrial cannabinoid receptor type 1 (CB1R) expression is disrupted in women with endometriosis and in isolated stromal cells exposed to 2,3,7,8tetrachlorodibenzopdioxin (TCDD).Fertil Steril,2012,98(4):948-956.e1.
[11]Maia J,Almada M,Silva A,et al.The endocannabinoid system expression in the female reproductive tract is modulated by estrogen.J Steroid Biochem Mol Biol,2017,174:40-47.
[12]Schander JA,Correa F,Bariani MV,et al.A role for the endocannabinoid system in premature luteal regression and progesterone withdrawal in lipopolysaccharideinduced early pregnancy loss model.Mol Hum Reprod,2016,22(11):800-808.
[13]Di Blasio AM,Vignali M,Gentilini D.The endocannabinoid pathway and the female reproductive organs.J Mol Endocrinol,2013,50(1):R1-9.
[14]Correa F,Wolfson ML,Valchi P,et al.Endocannabinoid system and pregnancy.Reproduction,2016,152(6):R191-R200.
[15]Hao M,Liu X,Guo SW.Adenomyosis in mice resulting from mechanically or thermally induced endometrialmyometrial interface disruption and its possible prevention.Reprod Biomed Online,2020,41(5):925-942.
[16]Elliott DM,Singh N,Nagarkatti M,et al.Cannabidiol attenuates experimental autoimmune encephalomyelitis model of multiple sclerosis through induction of myeloidderived suppressor cells.Front Immunol,2018,9:1782.
[17]Oláh A,Szekanecz Z,Bíró T.Targeting cannabinoid signaling in the immune system:“high”ly exciting questions,possibilities,and challenges.Front Immunol,2017,8:1487.
[18]Iuvone T,De Filippis D,Di Spiezio Sardo A,et al.Selective CB2 upregulation in women affected by endometrial inflammation.J Cell Mol Med,2008,12(2):661-670.
[19]Sen A,Kushnir VA,Barad DH,et al.Endocrine autoimmune diseases and female infertility.Nat Rev Endocrinol,2014,10(1):37-50.
[20]Cui N,Wang C,Zhao Z,et al.The roles of anandamide,fatty acid amide hydrolase,and leukemia inhibitory factor on the endometrium during the implantation window.Front Endocrinol (Lausanne),2017,8:268.
[21]Bambang KN,Lambert DG,Lam PMW,et al.Immunity and early pregnancy events:are endocannabinoids the missing link?J Reprod Immunol,2012,96(1-2):8-18.
[22]Pagano E,Orlando P,Finizio S,et al.Role of the endocannabinoid system in the control of mouse myometrium contractility during the menstrual cycle.Biochem Pharmacol,2017,124:83-93.
[23]Zhou L,Zhou S,Yang P,et al.Targeted inhibition of the type 2 cannabinoid receptor is a novel approach to reduce renal fibrosis.Kidney Int,2018,94(4):756-772.
[24]Sanchez AM,Quattrone F,Pannese M,et al.The cannabinoid receptor CB1 contributes to the development of ectopic lesions in a mouse model of endometriosis.Hum Reprod,2017,32(1):175-184.

备注/Memo

备注/Memo:
基金项目:国家自然科学基金(81571412);首都医科大学附属北京妇产医院中青年学科骨干培养专项(FCYY201920);首都医科大学临床医学高精尖学科建设项目(1192070309)**通讯作者,Email:duanhua@ccmu.edu.cn
更新日期/Last Update: 2021-12-09