慢性前列腺炎大鼠行为学及L5～S2脊段P物质和神经激肽-1受体表达的研究
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摘要
目的:研究慢性前列腺炎(CP)大鼠模型行为学表现及其L5～S2脊段P物质(SP)和神经激肽-1受体(NK-1R)的表达。方法:成年雄性SD大鼠40只,随机分成对照组、45 d模型组、60 d模型组和90 d模型组,每组10只。采用开野试验和糖水消耗试验观察各组大鼠的行为学表现,测量各组大鼠前列腺指数,ELISA法测定大鼠血清TNF-α、IL-1β、IL-2和IL-10含量,光镜观察前列腺组织形态学变化,免疫组化检测L5～S2脊髓SP及NK-1R的表达。结果:与对照组相比,45、60 d模型组大鼠水平运动评分、垂直运动评分和糖水消耗量呈下降趋势,但无显著性差异;而90 d模型组显著下降(P<0.05)。与对照组相比,45、60、90 d模型组大鼠前列腺指数显著下降(P均<0.05);与45 d和60 d模型组相比,90 d模型组前列腺指数显著下降(P均<0.05)。光镜观察,对照组前列腺组织未见炎细胞浸润,随着造模时间的延长,前列腺组织出现明显水肿,淋巴细胞增加显著。与对照组比较,45、60、90 d模型组大鼠血清TNF-α、IL-1β、IL-2和IL-10水平显著增加(P均<0.05)。免疫组化结果显示,SP和NK-1R主要表达于脊髓背角,各模型组SP和NK-1R的表达水平显著高于对照组(P均<0.05)。与45 d和60 d模型组相比,90 d模型组SP和NK-1R的表达水平显著升高(P均<0.05)。结论:CP模型大鼠出现抑郁行为学表现,血清TNF-α、IL-1β、IL-2和IL-10水平显著升高,L5～S2脊髓背角SP及NK-1R表达上调,且不同时段变化趋势一致,提示不同时段CP模型大鼠的行为学表现与L5～S2脊段SP及其受体表达水平存在相关性。
Objective: To investigate the correlation between the behavioral performance and the expressions of substance P(SP) and neurokinin-1 receptor(NK-1 R) in the posterior horn of the L5-S2 spinal cord in rats with chronic prostatitis(CP). Methods: A CP model was made in 30 adult male SD rats by intraperitoneal injection of 0.5 ml dyphtheria pertussis tetanus(DPT) vaccine and mixed solution of 1 ml prostatein extract and complete adjuvant in a 1∶1 ratio, and another 10 rats were injected with the same volume of normal saline as controls. At 45(n = 10), 60(n = 10) and 90 days(n = 10) after modeling, the behavioral changes of the rats were observed by open-field and sucrose consumption tests, the prostatic indexes and levels of serum TNF-α, IL-1β, IL-2 and IL-10 were obtained, and the expressions of SP and NK1-R in the L5-S2 spinal cord were determined by immunohistochemistry. Results: Compared with the controls, the CP model rats showed obviously decreased horizontal and vertical movement scores and sucrose consumption, particularly in the 90 d group(P < 0.05), significantly reduced prostatic indexes in the 45 d, 60 d and 90 d groups(all P < 0.05), even lower in the 90 d than in the 45 d and 60 d groups(P < 0.05). Edema and lymphocytes were increased in the prostatic tissue with the prolonged time of modeling. The levels of serum TNF-α, IL-1β, IL-2 and IL-10 were markedly elevated in all the CP rats as compared with those in the controls(P < 0.05), and so were the expressions of SP and NK-1 R in the L5-S2 spinal cord(P < 0.05), even more significantly in the 90 d than in the 45 d and 60 d groups(P < 0.05). Conclusion: Rats with chronic prostatitis are characterized by behavioral manifestation of depression, increased levels of serum TNF-α, IL-1β, IL-2 and IL-10, and a time-dependent upregulation of the expressions of SP and NK-1 R in the posterior horn of the L5-S2 spinal cord, which suggests a correlation between the behavioral performance and the expressions of SP and NK-1 R in the L5-S2 spinal cord of the rats. Natl J Androl, 2019, 25(6): 489-495
Objective: To investigate the correlation between the behavioral performance and the expressions of substance P(SP) and neurokinin-1 receptor(NK-1 R) in the posterior horn of the L5-S2 spinal cord in rats with chronic prostatitis(CP). Methods: A CP model was made in 30 adult male SD rats by intraperitoneal injection of 0.5 ml dyphtheria pertussis tetanus(DPT) vaccine and mixed solution of 1 ml prostatein extract and complete adjuvant in a 1∶1 ratio, and another 10 rats were injected with the same volume of normal saline as controls. At 45(n = 10), 60(n = 10) and 90 days(n = 10) after modeling, the behavioral changes of the rats were observed by open-field and sucrose consumption tests, the prostatic indexes and levels of serum TNF-α, IL-1β, IL-2 and IL-10 were obtained, and the expressions of SP and NK1-R in the L5-S2 spinal cord were determined by immunohistochemistry. Results: Compared with the controls, the CP model rats showed obviously decreased horizontal and vertical movement scores and sucrose consumption, particularly in the 90 d group(P < 0.05), significantly reduced prostatic indexes in the 45 d, 60 d and 90 d groups(all P < 0.05), even lower in the 90 d than in the 45 d and 60 d groups(P < 0.05). Edema and lymphocytes were increased in the prostatic tissue with the prolonged time of modeling. The levels of serum TNF-α, IL-1β, IL-2 and IL-10 were markedly elevated in all the CP rats as compared with those in the controls(P < 0.05), and so were the expressions of SP and NK-1 R in the L5-S2 spinal cord(P < 0.05), even more significantly in the 90 d than in the 45 d and 60 d groups(P < 0.05). Conclusion: Rats with chronic prostatitis are characterized by behavioral manifestation of depression, increased levels of serum TNF-α, IL-1β, IL-2 and IL-10, and a time-dependent upregulation of the expressions of SP and NK-1 R in the posterior horn of the L5-S2 spinal cord, which suggests a correlation between the behavioral performance and the expressions of SP and NK-1 R in the L5-S2 spinal cord of the rats. Natl J Androl, 2019, 25(6): 489-495
引文
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[7] 王宇阳,任晓暄,郑瑀,等.不同电针频率对慢性应激抑郁刺激模型大鼠行为学和下丘脑5-羟色胺水平的影响.长春中医药大学学报,2018,34(1):19-22.
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[11] 潘东山,杨水法,杨恩明,等.慢性前列腺炎患者抑郁状态调查及小剂量抗抑郁药物的治疗效果观察.慢性病学杂志,2017,18(11):1204-1207.
[12] Quan X,Luo H,Fan H,et al.Brain-derived neurotrophic factor contributes to colonic hypermotility in a chronic stress rat model.Dig Dis Sci,2015,60(8):2316-2326.
[13] Ayanwuyi LO,Stopponi S,Ubaldi M,et al.Neurokinin 1 receptor blockade in the medial amygdala attenuates alcohol drinking in rats with innate anxiety but not in Wistar rats.Br J Pharmacol,2015,172(21):5136-5146.
[14] 中药有效成分治疗慢性前列腺炎的免疫机制,等.前列安丸对慢性非细菌性前列腺炎大鼠前列腺组织IL-1β、IL-10及TNF-α的影响.中国中西医结合杂志,2015,35(10):1223-1227.
[15] 王浩,周玉春,薛建国.中药有效成分治疗慢性前列腺炎的免疫机制.中华男科学杂志,2016,22(1):63-66.
[16] 谢晓燕,张娟,赵莉.疼痛和抑郁共患机制的研究进展.中国疼痛医学杂志,2016,22(1):50-54.
[2] 那彦群,叶章群,孙颖浩,等.中国泌尿外科疾病诊断治疗指南(2014版).北京:人民卫生出版社,2013.
[3] 潘成年,陈伟民,黄峰平,等.中医药配合心理干预疗法治疗56例慢性前列腺炎的临床观察-附抑郁和焦虑状况分析.中医临床研究,2017,9(14):85-88.
[4] 傅伟,李其信,游旭军,等.基于数据挖掘分析李其信治疗慢性前列腺炎用药规律研究.山西中医,2018,34(2):42-45.
[5] Garcia-Recio S,Gascón P.Biological and pharmacological aspects of the NK1-Receptor.Biomed Res Int,2015,2015:495704.
[6] 郝丽亚,刘丽,白现广,等.P物质及其神经激肽-1 受体在慢性非细菌性前列腺炎大鼠 L5-S2 脊段的表达.中华男科学杂志,2016,22(7):602-607.
[7] 王宇阳,任晓暄,郑瑀,等.不同电针频率对慢性应激抑郁刺激模型大鼠行为学和下丘脑5-羟色胺水平的影响.长春中医药大学学报,2018,34(1):19-22.
[8] Magri V,Marras E,Restelli A,et al.Multimodal therapy for category III chronic prostatitis/chronic pelvic pain syndrome in UPOINTS phenotyped patients.Exp Ther Med,2015,9(3):658-666.
[9] Magistro G,Wagenlehner FM,Grabe MA,et al.Contemporary management of chronic prostatitis/chronic pelvic pain syndrome.Eur Urol,2016,69(2):286-297.
[10] 魏汝深.疏肝活血法治疗慢性非细菌性前列腺炎的临床研究.双足与保健,2018,2:123-124.
[11] 潘东山,杨水法,杨恩明,等.慢性前列腺炎患者抑郁状态调查及小剂量抗抑郁药物的治疗效果观察.慢性病学杂志,2017,18(11):1204-1207.
[12] Quan X,Luo H,Fan H,et al.Brain-derived neurotrophic factor contributes to colonic hypermotility in a chronic stress rat model.Dig Dis Sci,2015,60(8):2316-2326.
[13] Ayanwuyi LO,Stopponi S,Ubaldi M,et al.Neurokinin 1 receptor blockade in the medial amygdala attenuates alcohol drinking in rats with innate anxiety but not in Wistar rats.Br J Pharmacol,2015,172(21):5136-5146.
[14] 中药有效成分治疗慢性前列腺炎的免疫机制,等.前列安丸对慢性非细菌性前列腺炎大鼠前列腺组织IL-1β、IL-10及TNF-α的影响.中国中西医结合杂志,2015,35(10):1223-1227.
[15] 王浩,周玉春,薛建国.中药有效成分治疗慢性前列腺炎的免疫机制.中华男科学杂志,2016,22(1):63-66.
[16] 谢晓燕,张娟,赵莉.疼痛和抑郁共患机制的研究进展.中国疼痛医学杂志,2016,22(1):50-54.
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