五羟色胺受体的免疫调节功能研究
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摘要
五羟色胺(5-hydroxytryptamine，5-HT)又称血清素(Serotonin)，是一种单胺类神经调质。近年来，研究发现免疫系统中也存在5-HT受体及其转运体，5-HT通过与其受体相互作用参与调节免疫系统的活动。本课题旨在探讨5-HT受体的免疫调节功能，研究主要内容包括：
1.采用血凝抑制实验方法，检测不同剂量的5-HT1A受体激动剂萘哌地尔和5-HT2A受体拮抗剂富马酸喹硫平对雏鸡接种苗后新城疫HI抗体滴度的影响。实验结果显示：与21日龄对照组相比，5-HT1A受体激动剂中低剂量组(0.42mg/只/天、0.21mg/只/天)抗体效价低于对照组,高剂量组(0.84mg/只/天)高于对照组，而5-HT2A受体拮抗剂各组(1.64mg/只/天、0.82mg/只/天、0.41mg/只/天)均高于对照组，但结果均不显著。
2.采用MTT法，检测5-HT1AR激动剂盐酸钉螺环酮、拮抗剂盐酸普萘洛尔和5-HT2AR激动剂盐酸DOI、拮抗剂酮色林对绵羊外周血T淋巴细胞体外转化增殖的影响。实验结果显示：5-HT1A受体拮抗剂和5-HT2A受体激动剂在10μM至100μM浓度范围内剂量依赖性地抑制ConA刺激T淋巴细胞增殖；并显著促进静息状态淋巴细胞增殖活性。表明，5-HT1A受体和5-HT2A受体都参与了淋巴细胞增殖的调节，两者作用相反。
3.采用MTT法，检测5-HT1A、5-HT2AR反义寡核苷酸对绵羊外周血T淋巴细胞体外转化增殖的影响。实验结果显示：5-HT1AR反义寡核苷酸浓度为0.4μM时可显著抑制ConA刺激T淋巴细胞增殖，5-HT2AR反义寡核苷酸浓度为0.4μM时可显著促进ConA刺激T淋巴细胞增殖，而0.4μM的5-HT1AR和5-HT2AR正义寡核苷酸均显著促进ConA刺激T淋巴细胞增殖。
4.采用放射性免疫方法，检测5-HT1AR、5-HT2AR激动剂和拮抗剂对ConA刺激T淋巴细胞上清液IL-2和IL-4浓度的影响。实验结果显示：不同剂量的5-HT1AR、5-HT2AR激动剂和拮抗剂可显著升高或降低淋巴细胞分泌IL-2、IL-4量，无剂量依赖效应。
实验研究的主要结论如下：
1.5-HT受体可能参与调节雏鸡体液免疫。
2.5-HT1AR促进ConA刺激淋巴细胞增殖，5-HT2AR抑制ConA刺激淋巴细胞增殖。
3.抑制5-HT1A或激活5-HT2A受体可增强静息状态淋巴细胞增殖活性。
4.5-HT1AR、5-HT2AR可能参与调节淋巴细胞分泌IL-2和IL-4。
5-hydroxytryptamine (5-HT) also known as serotonin, is a monoamineneuromodulator.In recent years, studies have found the5-HT and its receptors also exists inimmune system,5-HT as an immunomodulatory factor perspective has been graduallyaccepted by people. To explore the issues of5-HT receptors on immune regulation function,research contents include:
1. We studied the effect of5-HT1A receptor agonists naftopidil and5-HT2A receptorantagonists quetiapine fumarate on boiler antibody titer afer inoculated Newcastle diseasevaccine by hemagglutination inhibition assay.The experimental result showed:Comparing tothe control group of21day old chickens, antibody titer of5-HT1A receptor agonist in midand low dose group (0.42mg every chick/day,0.21mg every chick/day) was lower than that inthe control group, high dose group (0.84mg every chick/day) was higher than that in controlgroup, while the5-HT receptor antagonist groups (1.64mg every chick/day,0.82mg everychick/day,0.41mg every chick/day) were higher than those in the control group, all theresults were not significant.
2.We studied the effect of5-HT1AR、5-HT2AR agonists and antagonists on ovineperipheral blood T lymphocyte transformation in vitro by MTT assay. The experimental resultshowed: Within10μM to100μM concentrations,5-HT1A receptor antagonist and5-HT2Areceptor agonists dose dependent inhibit ConA stimulated T lymphocyte proliferation, whilesignificantly promote lymphocyte proliferation activity in resting state.The result indicate that5-HT1A and5-HT2A receptors are involved in the opposite regulation of lymphocyteproliferation.
3. We also detected the effect of5-HT1AR ASODN and5-HT2AR ASODN on ovineperipheral blood lymphocyte proliferation in vitro by MTT assay. The experimental resultshowed:0.4μM5-HT1AR ASODN significantly inhibit ConA stimulated T lymphocyteproliferation,0.4μ M5-HT2AR ASODN significantly promote ConA stimulated Tlymphocyte proliferation,0.4μM5-HT1AR、5-HT2AR SODN both significantly promoteConA stimulated T lymphocyte proliferation.While，5-HT1AR and5-HT2AR ASODN has significantly increased lymphocyte proliferation activity in resting state.
4.We detected the effect of5-HT1AR、5-HT2AR agonists and antagonists on IL-2、IL-4concentration of culture liquid of ovine peripheral blood lymphocyte. The experimental resultshowed: Different dose of5-HT1AR、5-HT2AR agonists and antagonists can significantlyincrease or decrease IL-2, IL-4concentrations of lymphocyte culture liquid, but there is nodose dependent effect.
These chief conclusions below are yielded from this experimental study:
1.5-HT receptor may be involved in the regulation of humoral immune in chicks.
2.5-HT1AR promote ConA stimulated lymphocyte proliferation,5-HT2AR inhibitConA stimulated lymphocyte proliferation.
3. Inhibition of5-HT1AR or activation of5-HT2AR can enhance proliferation activatyof resting lymphocyte.
4.5-HT1AR、5-HT2AR may be involved in the regulation of the secretion of IL-2andIL-4by lymphocytes.
1.采用血凝抑制实验方法，检测不同剂量的5-HT1A受体激动剂萘哌地尔和5-HT2A受体拮抗剂富马酸喹硫平对雏鸡接种苗后新城疫HI抗体滴度的影响。实验结果显示：与21日龄对照组相比，5-HT1A受体激动剂中低剂量组(0.42mg/只/天、0.21mg/只/天)抗体效价低于对照组,高剂量组(0.84mg/只/天)高于对照组，而5-HT2A受体拮抗剂各组(1.64mg/只/天、0.82mg/只/天、0.41mg/只/天)均高于对照组，但结果均不显著。
2.采用MTT法，检测5-HT1AR激动剂盐酸钉螺环酮、拮抗剂盐酸普萘洛尔和5-HT2AR激动剂盐酸DOI、拮抗剂酮色林对绵羊外周血T淋巴细胞体外转化增殖的影响。实验结果显示：5-HT1A受体拮抗剂和5-HT2A受体激动剂在10μM至100μM浓度范围内剂量依赖性地抑制ConA刺激T淋巴细胞增殖；并显著促进静息状态淋巴细胞增殖活性。表明，5-HT1A受体和5-HT2A受体都参与了淋巴细胞增殖的调节，两者作用相反。
3.采用MTT法，检测5-HT1A、5-HT2AR反义寡核苷酸对绵羊外周血T淋巴细胞体外转化增殖的影响。实验结果显示：5-HT1AR反义寡核苷酸浓度为0.4μM时可显著抑制ConA刺激T淋巴细胞增殖，5-HT2AR反义寡核苷酸浓度为0.4μM时可显著促进ConA刺激T淋巴细胞增殖，而0.4μM的5-HT1AR和5-HT2AR正义寡核苷酸均显著促进ConA刺激T淋巴细胞增殖。
4.采用放射性免疫方法，检测5-HT1AR、5-HT2AR激动剂和拮抗剂对ConA刺激T淋巴细胞上清液IL-2和IL-4浓度的影响。实验结果显示：不同剂量的5-HT1AR、5-HT2AR激动剂和拮抗剂可显著升高或降低淋巴细胞分泌IL-2、IL-4量，无剂量依赖效应。
实验研究的主要结论如下：
1.5-HT受体可能参与调节雏鸡体液免疫。
2.5-HT1AR促进ConA刺激淋巴细胞增殖，5-HT2AR抑制ConA刺激淋巴细胞增殖。
3.抑制5-HT1A或激活5-HT2A受体可增强静息状态淋巴细胞增殖活性。
4.5-HT1AR、5-HT2AR可能参与调节淋巴细胞分泌IL-2和IL-4。
5-hydroxytryptamine (5-HT) also known as serotonin, is a monoamineneuromodulator.In recent years, studies have found the5-HT and its receptors also exists inimmune system,5-HT as an immunomodulatory factor perspective has been graduallyaccepted by people. To explore the issues of5-HT receptors on immune regulation function,research contents include:
1. We studied the effect of5-HT1A receptor agonists naftopidil and5-HT2A receptorantagonists quetiapine fumarate on boiler antibody titer afer inoculated Newcastle diseasevaccine by hemagglutination inhibition assay.The experimental result showed:Comparing tothe control group of21day old chickens, antibody titer of5-HT1A receptor agonist in midand low dose group (0.42mg every chick/day,0.21mg every chick/day) was lower than that inthe control group, high dose group (0.84mg every chick/day) was higher than that in controlgroup, while the5-HT receptor antagonist groups (1.64mg every chick/day,0.82mg everychick/day,0.41mg every chick/day) were higher than those in the control group, all theresults were not significant.
2.We studied the effect of5-HT1AR、5-HT2AR agonists and antagonists on ovineperipheral blood T lymphocyte transformation in vitro by MTT assay. The experimental resultshowed: Within10μM to100μM concentrations,5-HT1A receptor antagonist and5-HT2Areceptor agonists dose dependent inhibit ConA stimulated T lymphocyte proliferation, whilesignificantly promote lymphocyte proliferation activity in resting state.The result indicate that5-HT1A and5-HT2A receptors are involved in the opposite regulation of lymphocyteproliferation.
3. We also detected the effect of5-HT1AR ASODN and5-HT2AR ASODN on ovineperipheral blood lymphocyte proliferation in vitro by MTT assay. The experimental resultshowed:0.4μM5-HT1AR ASODN significantly inhibit ConA stimulated T lymphocyteproliferation,0.4μ M5-HT2AR ASODN significantly promote ConA stimulated Tlymphocyte proliferation,0.4μM5-HT1AR、5-HT2AR SODN both significantly promoteConA stimulated T lymphocyte proliferation.While，5-HT1AR and5-HT2AR ASODN has significantly increased lymphocyte proliferation activity in resting state.
4.We detected the effect of5-HT1AR、5-HT2AR agonists and antagonists on IL-2、IL-4concentration of culture liquid of ovine peripheral blood lymphocyte. The experimental resultshowed: Different dose of5-HT1AR、5-HT2AR agonists and antagonists can significantlyincrease or decrease IL-2, IL-4concentrations of lymphocyte culture liquid, but there is nodose dependent effect.
These chief conclusions below are yielded from this experimental study:
1.5-HT receptor may be involved in the regulation of humoral immune in chicks.
2.5-HT1AR promote ConA stimulated lymphocyte proliferation,5-HT2AR inhibitConA stimulated lymphocyte proliferation.
3. Inhibition of5-HT1AR or activation of5-HT2AR can enhance proliferation activatyof resting lymphocyte.
4.5-HT1AR、5-HT2AR may be involved in the regulation of the secretion of IL-2andIL-4by lymphocytes.
引文
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