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他克莫司对大鼠自身免疫性前列腺炎的治疗作用及其机制

Therapeutic effect of Tacrolimus on autoimmune prostatitis in rat model and possible mechanism

摘要:

目的 探讨他克莫司对大鼠实验性自身免疫性前列腺炎(EAP)的治疗作用及其机制.方法 将SD大鼠随机分为对照组(C)、EAP模型组(M)、低剂量治疗组(L)和高剂量治疗组(H),各组再按给药时间分为2周(2W)和4周(4W)2个亚组.EAP模型造模成功后低剂量和高剂量治疗组分别给予他克莫司0.2 mg/(kg·d)和0.8 mg/(kg·d)灌胃,连续2周及4周.检测前列腺组织匀浆和血清中白细胞介素(IL)-2和巨噬细胞炎性蛋白(MIP)-1α的含量,观察前列腺、脾和胸腺组织形态学改变,计算前列腺、脾和胸腺的脏器系数.结果 他克莫司干预后组织形态学显示前列腺组织中炎症细胞减少,腺腔壁得到一定的修复.M2W、L2W和H2W组血清IL-2和MIP-1α分别为(156.80±19.11)、(124.56±17.20)、(114.46±20.65) ng/L和(164.99±22.25)、(112.03±19.90)、(104.91±11.91) ng/L;前列腺组织匀浆IL-2和MIP-1α分别为(219.26±23.11)、(191.56±19.08)、(186.63±20.90) ng/L和(216.46±18.50)、(196.55±17.84)、(194.74±18.14) ng/L.M4W、L4W和H4W组血清IL-2和MIP-1α分别为(156.23±19.83)、(129.27±17.25)、(134.26±16.11) ng/L;(157.93±34.55)、(159.09±29.17)、(154.54±29.85) ng/L;前列腺组织匀浆IL-2和MIP-1α分别为(217.92±23.23)、(186.07±11.56)、(180.37±18.26) ng/L; (209.66±14.65)、(186.17±17.79)、(186.16±18.27) ng/L.除4周组血清MIP-1 α外差异均有统计学意义(P<0.05).结论 他克莫司减少EAP大鼠模型前列腺组织中的炎症细胞,这一作用可能与其抑制IL-2的产生和T细胞的活化有关.

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abstracts:

Objective To explore the efficacy of tacrolimus in treating experimental autoimmune prostatitis (EAP) in rat model and the possible mechanism.Methods SD rats were randomly divided into 4 groups:normal control group,EAP model group,low-dose treatment group,high-dose treatment group.According to administration durations,each group was further divided into two subgroups:2-week group and 4-week group.After successful modeling,rats in low-dose treatment group and high-dose group underwent gastric perfusion with 0.2 mg/(kg·day) and 0.8 mg/(kg·day) tacrolimus respectively for 2 and 4 weeks in a successive way.Concentrations of interleukin (IL)-2 and macrophage inflammatory protein-1α (MIP-1α) in the homogenate of prostatic tissue and serum were tested.Histomorphological changes of prostatic tissue,spleen and thymus gland were observed,with their viscera coefficients being calculated.Results After the intervention of tacrolimus,a decrease in inflammatory cells in prostatic tissue was revealed histomorphologically and glandular cavity wall was repaired to some extent.The concentrations of IL2 were ( 156.80 ± 19.11 ),( 124.56 ± 17.20) and ( 114.46 ± 20.65) ng/L in the serum of M2W,L2W and H2W groups,and MIP-1 α concentrations were ( 164.99 ± 22.25 ),( 112.03 ± 19.90) and ( 104.91 ± 11.91 ) ng/L,respectively.As for the homogenate of prostatic tissue,IL-2 and MIP-1α levels stood at (219.26±23.11),(191.56±19.08),(186.63 ±20.90) ng/L,and (216.46 ±18.50),(196.55 ±17.84),( 194.74 ± 18.14) ng/L respectively.In comparison,in M4W,LAW and H4W groups,concentrations of the two substances were ( 156.23 ± 19.83),( 129.27 ± 17.25),( 134.26 ± 16.11 ) ng/L and (157.93 ±34.55),(159.09 ±29.17),(154.54 ±29.85) ng/L,respectively.In the homogenate of prostatic tissue,data were (217.92 ±23.23),(186.07 ± 11.56),(180.37 ± 18.26) ng/L and (209.66 ±14.65),( 186.17 ± 17.79),( 186.16 ± 18.27) ng/L,respectively.All differences were statistically significant except MIP-1α level in the serum of 4-week subgroup.Conclusion Tacrolimus can reduce the number of inflammatory cells in prostatic tissue in EAP rat model,which may be related to its suppression of the production of IL-2 and activation of T cells.

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作者: 袁道彰 [1] 苏泽轩 [1] 钟玲 [1] 刘玉峰 [1] 陈洁 [1] 丁泓文 [1] 都兴华 [1]
期刊: 《中华实验外科杂志》2012年29卷2期 282-285页 ISTICPKU
分类号: R737.25
栏目名称: 实验研究
DOI: 10.3760/cma.j.issn.1001-9030.2012.02.042
发布时间: 2012-04-20
基金项目:
国家高技术研究发展计划(863计划)项目 广东省"十一五"医学重点专科基金
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