断乳对小鼠乳腺固有免疫的影响
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摘要
乳腺炎是奶牛最常见的疾病之一,严重影响乳的品质,甚至危及人类健康。奶牛在干乳期极易感染发生乳腺炎,主要原因是由于断乳后乳腺的结构和功能发生了巨大调整,乳腺局部免疫系统改变,导致病原菌入侵引发感染。为了研究断乳对小鼠乳腺固有免疫的影响,本试验以小鼠为模式动物,分别测定自然和强制断乳后五个时间点(0d、1d、2d、3d、4d、5d)乳腺组织中固有免疫相关因素的变化。本研究阐明了断乳对乳腺固有免疫的影响,为研究断乳早期乳腺固有免疫的特性提供理论,以便针对性地降低干乳期乳房炎发生率提供理论参考。主要结果如下:
     自然断乳对固有免疫的影响:自然断乳后,IL-1β、IL-2、IL-6、G-CSF呈下调-上调-下调的变化趋势;TNF-α转录持续下调;KC(IL-8)转录呈先升高后降低的变化;LP活性持续升高,但和强制断乳相反;iNOS变化不显著,趋势与促炎因子一致;NAGase和AKP活性呈升高趋势,与强制断乳后相同。E2和PRL水平持续升高;P4水平1d时有所升高,2d时下降,此后持续升高;Cor短暂升高后恢复至断乳0d水平。
     强制断乳对固有免疫的影响:LF、KC和G-CSF趋势基本一致,断乳后呈上调-下调趋势;IL-1β和IL-2变化与自然断乳一致;TNF-α转录下调后上调,差异不显著。强制断乳引起LP出现短暂升高,与文献一致。iNOS短暂升高后下降,水平并没有持续上升,这种变化趋势和XOD一致。AKP和NAGase活性迅速升高。断乳0d时E2、P4、PRL和Cor水平较低,断乳后,E2和PRL持续迅速升高,PRL升高11倍;P4水平最后趋于降低;Cor降低后恢复至断乳0d水平。
     研究发现,断乳后固有免疫相关因素转折性变化主要集中于断乳1~3内,除部分持续升高的因子外,5d时多数因素水平恢复至0d水平。炎性因子转录水平出现升高,但5d时恢复为断乳0d水平,多数抗菌蛋白在断乳初期有降低趋势,部分激素水平升高可能为异常改变。分析得出:断乳初期乳腺可能有炎性变化趋势,免疫功能受损,但随着退化的完成,免疫功能可能逐渐得到恢复。两种断乳方式引起部分因子变化模式截然不同,提示两者机制具有差异。
Mastitis is one of the most common diseases of cows, seriously affecting the quality of milk, and even endangering human health. The incidence of mastitis is high at early weaning stage. Mastitis incidence is high at early weaning stage. The main reason is that structure and function of post-weaning mammary gland undergone drastic adjustments, and mammary gland local immune system changes at the same time, which result in invasion of pathogens causing infection. In order to understand effect of weaning on mammary gland innate immunity, this experiment selected mouse as model animal, and measured pro-inflammatory and anti-inflammatory factor related to mammary gland innate immunity at five time points (0d, 1d, 2d, 3d, 4d, 5d) after natural weaning and forced weaning respectively. The study had revealed effect of weaning on mammary gland innate immunity, which offered a theoretical basis for investigating properties of mammary gland innate immunity at early post-weaning stage and providing the scientific basis for increasing mammary gland immunity to decrease mastitis incidence. The results were as follows:
     First, effects of natural weaning on innate immunity: After natural weaning, the tends of IL-1β, IL-2, IL-6 and G-CSF transcription in mammary gland was consistent and was up-down-up; TNF-αtranscription decreased continually; and KC(IL-8) level first increased then declined. LP activity continued to rise, but was opposite compared with forced weaning; iNOS did not change significantly and had a same trends with pro-inflammatory cytokines; NAGase and AKP activity tended to increase that is consistent with forced weaning; E2, P4 and PRL levels continued to rise, and Cor restored to the level of weaning 0d.
     Second, effects of forced weaning on innate immunity: After weaning, the changes of IL-1 and IL-2 were consistent with that of natural weaning; IL-6 decline after a brief increase; TNF-αtranscription level up-regulate after a down regulation but the difference was not significant; LF, KC and G-CSF had the same change and showed a up-down trend. LP activity reduced after a brief decrease; the changes of XOD and iNOS activity were consistent trend and manifested a downtrend as a whole. AKP and NAGase activity increased rapidly after weaning. E2, P4, PRL and Cor levels were low at weaning 0d, E2 and PRL increased rapidly after weaning, PRL increased by 11 times; P4 increased in wav form; Cor decreased rapidly and then recovered to the weaning 0d level.
     This study showed that factors related to innate immunity after weaning taken place turning changes on weaning 1 to 3d, in addition to some factors keeping continually rise, the content of majority factors recovery to the level of weaning 0d. Inflammatory factors transcription increased, but they recovered to 0d levels at weaning 0d 5d, the majority of antibacterial proteins had a lower content in early weaning, and part of the elevated hormone levels may be abnormal. Analysis shows: inflammatory early trends may exist in mammary gland at the early period of weaning, immune function may be impaired, but immune function may gradually be restored along with the completion of degradation. Analysis shows: inflammatory early trends may exist in mammary gland at the early period of weaning, immune function may be impaired, but immune function may gradually be restored along with the completion of degradation. Some changes of factors in patterns caused by two weaning methods were totally opposite, suggesting that their mechanisms are different.
引文
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