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突变兰尼碱受体猪的束缚对应激相关激素和血液自然杀伤细胞细胞毒性的影响。

Restraint effects on stress-related hormones and blood natural killer cell cytotoxicity in pigs with a mutated ryanodine receptor.

机构信息

Department of Animal Physiology, University of Gdansk, 80-822 Gdansk, Poland.

出版信息

Domest Anim Endocrinol. 2013 May;44(4):195-203. doi: 10.1016/j.domaniend.2013.02.003. Epub 2013 Mar 16.

Abstract

A mutation in the ryanodine receptor gene (RYR1) of the calcium release channel is responsible for increased stress susceptibility in pigs. In the present study, the relation of a mutation in RYR1 with the neuroendocrine (stress-related hormone) response and the immune defense represented by natural killer cell cytotoxicity (NKCC) during a 4-h restraint and recovery phase in 60 male pigs was investigated. Blood samples were collected from pigs previously divided into RYR1 genotypes (nn, Nn, NN), based on PCR amplification and restriction analyses. The blood samples collected during the restraint and recovery phases of the experiment were used to determine NKCC ((51)Cr-release assay), large granular lymphocyte number (hematologic method), and plasma concentrations of prolactin (PRL), GH, ACTH, and cortisol (COR) (by specific RIA). The greatest degree of NKCC response (P < 0.05) to restraint stress relative to controls was observed for the stress-susceptible homozygote group (nn). Measures of stress-related hormones were positively correlated with NKCC during the entire experimental period (P < 0.001 for all investigated hormones) in the nn group. Immunostimulatory effects in the early (0-60 min) phase of restraint were associated with increased hormone responses, especially PRL and GH. In the late (180-240 min) phase of stress and the recovery phase (480 min), a decrease in immune response was accompanied by an elevated COR response in all RYR1 genotypes. Moreover, divergent responses of both PRL (greatest in nn, P < 0.001) and GH (greatest in NN, P < 0.001) to the 4-h restraint were observed. Our results suggest that stress-susceptible RYR1-mutated homozygotes develop a greater level of immune defense, including cytotoxic activity of NK cells, and accompanied by more pronounced stress-induced changes in neuroendocrine response than stress-resistant heterozygous (Nn) and homozygous (NN) pigs.

摘要

钙离子释放通道的兰尼碱受体基因(RYR1)突变可导致猪对压力更敏感。本研究旨在探讨RYR1 突变与神经内分泌(应激相关激素)反应以及以自然杀伤细胞细胞毒性(NKCC)为代表的免疫防御之间的关系,共纳入 60 头雄性猪,实验分为 4 小时束缚和恢复期,根据聚合酶链反应(PCR)扩增和限制性分析将猪分为 RYR1 基因型(nn、Nn、NN)。在实验的束缚和恢复期采集血液样本,用于测定 NKCC(51Cr 释放试验)、大颗粒淋巴细胞数(血液学方法)和催乳素(PRL)、生长激素(GH)、促肾上腺皮质激素(ACTH)和皮质醇(COR)的血浆浓度(特异性放射免疫分析)。相对于对照组,应激敏感纯合子组(nn)对束缚应激的 NKCC 反应最强烈(P<0.05)。在整个实验期间,与 NKCC 呈正相关(所有研究激素 P<0.001)。在束缚的早期(0-60 分钟)阶段,免疫刺激作用与激素反应增加有关,尤其是 PRL 和 GH。在应激和恢复期的后期(180-240 分钟和 480 分钟),所有 RYR1 基因型的免疫反应下降伴随着 COR 反应升高。此外,PRL(nn 组最大,P<0.001)和 GH(NN 组最大,P<0.001)对 4 小时束缚的反应存在明显差异。我们的结果表明,应激敏感的 RYR1 突变纯合子猪会产生更高水平的免疫防御,包括 NK 细胞的细胞毒性活性,并伴有更明显的应激诱导的神经内分泌反应变化,而应激抗性的杂合子(Nn)和纯合子(NN)猪则没有。

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