天府肉鸭中枢免疫器官胚胎及胚后发育期细胞凋亡及神经肽表达的研究
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摘要
本研究选用天府肉鸭150只,共分30个组,其中胚胎期分17个组(12～28天胚龄,每一胚龄为一组),胚后期分13个组(0、1、3、5、8、11、14、17、20、23、26、29、32周龄)。采用形态计量法,光镜、透射电镜、免疫组化、末端脱氧核糖核酸转移酶标记、原位杂交等技术对天府肉鸭中枢免疫器官胚胎及胚后期形态组织结构、细胞增殖与凋亡以及神经肽的表达进行动态观察与研究,同时重点观察了凋亡蛋白及其基因表达的动态变化。结果如下:
1.腔上囊和胸腺胚胎及胚后发育的形态组织结构表现出明显增龄变化特性,其中胚后发育可分为继续发育期(0～8周龄)、成熟持续期(腔上囊为8～14周龄,胸腺为8～17周龄)和退化期(腔上囊为17～32周龄;胸腺为20～32周龄)。26天胚龄腔上囊和胸腺组织分化基本趋于完善;1～3周龄和3～5周龄分别为腔上囊和胸腺胚后发育的高峰期;胚后8周龄二者发育达最大。小结相关上皮(FAE)的胚后发育具有增龄变化特性,参与了胚后腔上囊滤泡皮质部的进一步发育,并与腔上囊的退化有关。胸腺中存在胸腺小体和上皮细胞囊,后者数量多且具有多种形态和功能,二者是鸭胸腺基质中的重要组成成分。腔上囊退化时间较胸腺早、退化速度较胸腺快。
2.在腔上囊中,滤泡皮质淋巴细胞胞凋亡率基本呈上升(22天胚龄～新生雏),恒定(新生雏～胚后3周龄),下降(3～5周龄),恒定(5～14周龄),再上升(14～29周龄)的变化规律;滤泡髓质淋巴细胞凋亡率变化规律与皮质相似,但在1～3周龄显著升高。腔上囊滤泡皮质淋巴细胞凋亡率在22天胚龄～胚后14周龄显著低于髓质,而在胚后17～29周龄则明显高于髓质。在胸腺中,胸腺小叶皮质和髓质淋巴细胞凋亡率呈恒定(22～26天胚龄)、上升(26天胚龄～胚后8周龄),恒定(8～17周龄)、再上升(17～32周龄)的变化规律;各组胸腺皮质淋巴细胞凋亡率均高于髓质。腔上囊和胸腺淋巴细胞自然凋亡的超微结构及自然凋亡过程基本一致。淋巴细胞发生凋亡时,细胞核变化最明显,呈现多种形态。在腔上囊中,滤泡皮质和髓质淋巴细胞增殖率在胚胎期呈上升趋势,在胚后期呈下降趋势;各组滤泡皮质淋巴细胞增殖率均显著低于髓质。在胸腺中,皮质和髓质淋巴细胞增殖率在胚胎和胚后期均呈下降态势;各组皮质淋巴细胞增殖率均显著高于髓质。
3.在腔上囊中,滤泡皮、髓质淋巴细胞Bcl-2阳性率以及Bcl-2/Bax值与其凋亡率之间呈反向变化关系(滤泡皮质在新生雏～胚后3周龄和5～14周龄;滤泡髓质在5～14周龄除外),而Caspase-3、Fas和FasL阳性率基本与其凋亡率呈方向一致的变化关系;Bax阳性率主要在5～29周龄与其凋亡率呈方向一致的变化关系。22天胚龄～胚后14周龄,各组腔上囊滤泡皮质淋巴细胞Bcl-2/Bax值均大于髓质,而Caspase-3、Fas和FasL阳性率则低于髓质,分别与各组皮质淋巴细胞凋亡率低于髓质呈反向和正向变化关系;胚后17～29周龄,各组皮质淋巴细胞Bcl-2/Bax值小于髓质、而Caspase-3、Fas和FasL阳性率则大于髓质,分别与各组皮质淋巴细胞凋亡率高于髓质呈反向和正向变化关系。在胸腺中,皮质和髓质淋巴细胞Bcl-2/Bax值在26天胚龄～胚后8周龄,17～32周龄与其凋亡率呈反向变化关系;Bcl-2阳性率主要在20～32周龄与凋亡率呈反向变化关系;Caspase-3、Bax、Fas阳性率与其凋亡率变化趋势基本一致,但Fas阳性率在3～8周龄与其凋亡率无明显对应关系。各组胸腺皮质淋巴细胞Bcl-2/Bax值均小于髓质,而Caspase-3、Fas阳性率则大于髓质,分别与各组皮质淋巴细胞凋亡率高于髓质呈反向和正向变化关系。在胚胎及胚后发育期,两种免疫器官中淋巴细胞P53阳性率以及胸腺淋巴细胞FasL阳性率均无增龄变化特性。
4.在腔上囊中,滤泡皮质和髓质淋巴细胞bcl-2mRNA阳性率仅在胚胎期与其Bcl-2蛋白阳性率的变化规律呈一致性;在胚胎及胚后发育过程中,滤泡皮质和髓质淋巴细胞bax mRNA阳性率与其蛋白阳性率的变化规律相同(滤泡髓质20～29周龄除外);两种基因与其蛋白的组织分布不同,其表达存在转录后调控。在胸腺胚胎及胚后发育过程中,皮质和髓质淋巴细胞bcl-2和bax mRNA阳性率均与其蛋白阳性率的变化规律相似;两种基因与其蛋白的组织分布一致,其表达涉及转录水平调控。
5.CGRP、VIP、SP、NPY、SS神经肽阳性细胞在腔上囊和胸腺中广泛分布,它们在两种免疫器官中的首次发生时间不同,其数量呈现一定的增龄变化规律。胸腺胚后发育过程中存在CGRP、VIP、SP、NPY肽能神经支配,优势分布于胸腺髓质。腔上囊中存在VIP神经纤维。腔上囊的FAE以及胸腺的胸腺小体和上皮细胞囊均可表达上述神经肽。
本试验结果表明:在胚胎及胚后发育过程中,天府肉鸭腔上囊和胸腺的形态组织结构、细胞增殖与凋亡、凋亡蛋白与基因以及神经肽的表达表现出明显的增龄变化特性。两种免疫器官通过细胞增殖、凋亡以及神经肽的表达共同调节T、B淋巴细胞的增殖、分化和成熟,参与鸭中枢免疫器官发育和退化的调控。Caspase-3、Bcl-2、Bax、Fas、FasL、P53凋亡蛋白及其bcl-2和baxmRNA凋亡基因的表达直接调控腔上囊和胸腺淋巴细胞的凋亡。本研究从多角度和多层次首次揭示了天府肉鸭中枢免疫器官发生、发育及退化的变化规律及调控机制,将为调节其免疫器官发育和稳定,制定合理的免疫程序提供理论依据。
In this study ,150 Tianfu ducks were divided into 30 groups as follows: 17 groups in the embryonic period (one group per day from 12 to 28 days embryonic stage), 13 groups after hatching(0、1、3、5、8、11、14、17、20、23、26、29、32 weeks) . Using morphological method, light and electron microscopy, immunohistochemisty, terminal deoxynucleotidyl transferase biotin-dUTP nick end labelling (TUNEL) and in sita hybridization techniques, the morphological structures, cell proliferation and apoptosis, apoptotic proteins and genes and neuropeptide expression during the embryonic and post embryonic development of the central immune organs of Tianfu duck were studied. All results are shown as follows:
1. The morphological and histological structures of the duck bursa of Fabricius and thymus underwent obvious age-related changes during the embryonic and post embryonic development. The post embryonic development of these organs was divided into three stages as follows: the continuous development period (from 0 to 8 weeks), the matured and sustained period (in the bursa: from 8 to 14 weeks; in the thymus: from 8 to 17 weeks) and the regressive period (in the bursa: from 17 to 32 weeks; in the thymus: from 20 to 32 weeks).At 26 days embryonic stage(ES), the bursa and thymus had almost possessed the matured histological structure. The bursa and thymus grew very rapidly from 1 to 3 weeks and 3 to 5 weeks after hatching (AH), respectively, and gained their maximum in size and absolute weight at 8 weeks AH. The growth of bursal follicle associated epithelium (FAE),taking part in the post embryonic growth of the follicle cortex and being related to the bursal regression, showed age-related changes during the post embryonic development. The thymic corpuscle and epithelial cyst, with the latter outnumbering the former and presenting several features, were important functional components of the thymic matrix in the duck thymus. The bursa of Fabricius regressed earlier and more quickly than the thymus.
2. In the bursa, the apoptosis ratios of lymphocytes in the follicle cortex followed a series of changes as rising (from 22 days ES to neonatal stage), dropping (from 3 to 5 weeks AH) and maintaining at a certain level (from 0 to 3 weeks and from 5 to 14 weeks AH), and increasing again(from 14 to 29 weeks AH). Increasing from 1 to 3 weeks AH, the changing pattern of the apoptosis ratios of lymphocytes in the follicle medullar in other groups was similar to those in the follicle cortex. The apoptosis ratios of busal lymphocytes in the medullar were significantly higher from 22 days ES to 14 weeks AH or lower from 17 to 29 weeks AH than those in the cortex. The apoptosis ratios of thymic lymphocytes in the cortex and medullar kept unchanged (from 22 to 26 days ES and from 8 to 17 weeks AH) and increased (from 26 days ES to 8 weeks AH, and from 17 to 32 weeks AH).In each group, the apoptosis ratios of thymic lymphocytes in the cortex were significantly higher than those in the medullar. The ultrastructure and process of lymphocytes apoptosis in the bursa were similar to those in the thymus. The nuclei of apoptotic lymphocytes with great changes presented different features. In the bursa, the proliferative indexes of lymphocytes in the follicle cortex and medullar increased during the embryonic development and decreased during the post embryonic development. Moreover, the proliferative indexes of bursal lymphocytes in the medullar were significantly higher than those in the cortex in each group. In the thymus, the proliferative indexes of lymphocytes in the cortex and medullar decreased during both the embryonic and post embryonic development. The proliferative indexes of thymic lymphocytes in the cortex were significantly higher than those in the medullar in each group.
3.In the bursa, the Bcl-2 positive ratios and the ratios of Bcl-2 and Bax of lymphocytes in the follicle cortex and medullar paralleled reversely with the apoptosis ratios of lymphocytes (except 26 days ES to 14 weeks AH and from 5 to 14 weeks AH in the follicle cortex, and from 5 to 14 weeks AH in the follicle medullar ). The Caspase-3, Bax, Fas and FasL positive ratios of lymphocytes in the follicle cortex and medullar paralleled positively with the apoptosis ratios of lymphocytes (except Bax positive ratios from 22 days ES to 5 weeks AH). Furthermore, the ratios of Bcl-2 and Bax of lymphocytes in the follicle cortex were significantly higher from 22 days ES to 14 weeks AH, and lower from 17 to 29 weeks than those in the follicle medullar, which paralleled reversely with the apoptosis indexes of lymphocytes in the follicle cortex and medullar. The positive ratios of Caspase-3, Fas and FasL of bursal lymphocytes in the follicle cortex were significantly lower from 22 days ES to 14 weeks AH, and higher from 17 to 29 weeks AH than those in the medullar, which paralleled positively with the apoptosis ratios of lymphocytes in the follicle cortex and medullar. In the thymus, the ratios of Bcl-2 and Bax of lymphocytes in the cortex and medullar paralleled reversely with the apoptosis ratios of lymphocytes from 26 days ES to 8 weeks AH and from 20 to 32 weeks AH. The Bcl-2 positive ratios of lymphocytes in the thymic cortex and medullar paralleled reversely with the apoptosis ratios of lymphocytes from 20 to 32 weeks AH. The positive ratios of Caspase-3 ,Bax and Fas of lymphocytes in the thymic cortex and medullar paralleled positively with the apoptosis indexes of lymphocytes(except Fas positive ratios from 3 to 8 weeks AH).The ratios of Bcl-2 and Bax, the positive ratios of Caspase-3 and Fas of thymic lymphocytes in the cortex were significantly lower or higher than those in the medullar in each group which paralleled reversely or positively with the apoptosis ratios of lymphocytes in the cortex and medullar, respectively. The P53 positive ratios of lymphocytes in the bursa and thymus showed no age-related changes during the embryonic and post embryonic development, so did the FasL positive ratios of lymphocytes in the thymus.
4. Only during embryonic development of the bursa did the change patterns of the positive ratios of bcl-2 mRNA of lymphocytes in the follicle cortex and medullar parallel positively with those of the positive ratios of Bcl-2 proteins. During the embryonic and post embryonic development of the bursa, the change patterns of the positive ratios of bax mRNA of lymphocytes in the follicle cortex and medullar were similar to those of the positive ratios of Bax proteins (except 20 to 29 weeks AH in the medullar). bcl-2 and bax mRNA in the bursa were different from those of their proteins in the tissue distribution, whose expression presented the regulative mechanism after transcription. During the embryonic and post embryonic development of the thymus, the bcl-2 and bax mRNA of lymphocytes in the thymic cortex and medullar were similar to those of the positive ratios of Bcl-2 and Bax proteins both in the changing pattern of their positive ratios and in their tissue distribution, whose expression appeared to be modulated transcriptionally.
5. The first expression being different, CGRP, VIP, SP, NPY, SS positive cells whose number underwent certain age-related changes were widely located in the bursa and thymus. CGRP, VIP, SP, NPY positive nerves with predominant distribution in the medullar region were occurred in the thymus during the post embryonic development. Only the VIP positive nerves were observed in the bursa. CGRP, VIP, SP, NPY, SS expressions were detected in the bursal FAE and the thymic corpuscles and epithelial cysts.
Based on the results mentioned above, it shows that the morphological and histological structures, cell proliferation and apoptosis, apoptotic proteins and genes and neuropeptide expression in the central immune organs of Tianfu duck undergo obvious age-related changes during the embryonic and post embryonic development. The cell proliferation, apoptosis and neuropeptide expression in these organs supervise and control the proliferation and differentiation of T, B lymphocytes cooperatively, which plays significant and regulatory roles in the development and regression of the duck central immune organs. Caspase-3, Bcl-2, Bax, Fas, FasL and P53 apoptotic proteins and bcl-2 and bax mRNA genes modulate the apoptosis of lymphocytes in the bursa and thymus. The changing patterns and regulatory mechanism of the whole development and regression of the central immune organs of Tianfu duck are studied systematically for the first time, which might provide the theoretical evidences for the modulation of their development and stabilization and formulation of the reasonable immune procedures.
1.腔上囊和胸腺胚胎及胚后发育的形态组织结构表现出明显增龄变化特性,其中胚后发育可分为继续发育期(0～8周龄)、成熟持续期(腔上囊为8～14周龄,胸腺为8～17周龄)和退化期(腔上囊为17～32周龄;胸腺为20～32周龄)。26天胚龄腔上囊和胸腺组织分化基本趋于完善;1～3周龄和3～5周龄分别为腔上囊和胸腺胚后发育的高峰期;胚后8周龄二者发育达最大。小结相关上皮(FAE)的胚后发育具有增龄变化特性,参与了胚后腔上囊滤泡皮质部的进一步发育,并与腔上囊的退化有关。胸腺中存在胸腺小体和上皮细胞囊,后者数量多且具有多种形态和功能,二者是鸭胸腺基质中的重要组成成分。腔上囊退化时间较胸腺早、退化速度较胸腺快。
2.在腔上囊中,滤泡皮质淋巴细胞胞凋亡率基本呈上升(22天胚龄～新生雏),恒定(新生雏～胚后3周龄),下降(3～5周龄),恒定(5～14周龄),再上升(14～29周龄)的变化规律;滤泡髓质淋巴细胞凋亡率变化规律与皮质相似,但在1～3周龄显著升高。腔上囊滤泡皮质淋巴细胞凋亡率在22天胚龄～胚后14周龄显著低于髓质,而在胚后17～29周龄则明显高于髓质。在胸腺中,胸腺小叶皮质和髓质淋巴细胞凋亡率呈恒定(22～26天胚龄)、上升(26天胚龄～胚后8周龄),恒定(8～17周龄)、再上升(17～32周龄)的变化规律;各组胸腺皮质淋巴细胞凋亡率均高于髓质。腔上囊和胸腺淋巴细胞自然凋亡的超微结构及自然凋亡过程基本一致。淋巴细胞发生凋亡时,细胞核变化最明显,呈现多种形态。在腔上囊中,滤泡皮质和髓质淋巴细胞增殖率在胚胎期呈上升趋势,在胚后期呈下降趋势;各组滤泡皮质淋巴细胞增殖率均显著低于髓质。在胸腺中,皮质和髓质淋巴细胞增殖率在胚胎和胚后期均呈下降态势;各组皮质淋巴细胞增殖率均显著高于髓质。
3.在腔上囊中,滤泡皮、髓质淋巴细胞Bcl-2阳性率以及Bcl-2/Bax值与其凋亡率之间呈反向变化关系(滤泡皮质在新生雏～胚后3周龄和5～14周龄;滤泡髓质在5～14周龄除外),而Caspase-3、Fas和FasL阳性率基本与其凋亡率呈方向一致的变化关系;Bax阳性率主要在5～29周龄与其凋亡率呈方向一致的变化关系。22天胚龄～胚后14周龄,各组腔上囊滤泡皮质淋巴细胞Bcl-2/Bax值均大于髓质,而Caspase-3、Fas和FasL阳性率则低于髓质,分别与各组皮质淋巴细胞凋亡率低于髓质呈反向和正向变化关系;胚后17～29周龄,各组皮质淋巴细胞Bcl-2/Bax值小于髓质、而Caspase-3、Fas和FasL阳性率则大于髓质,分别与各组皮质淋巴细胞凋亡率高于髓质呈反向和正向变化关系。在胸腺中,皮质和髓质淋巴细胞Bcl-2/Bax值在26天胚龄～胚后8周龄,17～32周龄与其凋亡率呈反向变化关系;Bcl-2阳性率主要在20～32周龄与凋亡率呈反向变化关系;Caspase-3、Bax、Fas阳性率与其凋亡率变化趋势基本一致,但Fas阳性率在3～8周龄与其凋亡率无明显对应关系。各组胸腺皮质淋巴细胞Bcl-2/Bax值均小于髓质,而Caspase-3、Fas阳性率则大于髓质,分别与各组皮质淋巴细胞凋亡率高于髓质呈反向和正向变化关系。在胚胎及胚后发育期,两种免疫器官中淋巴细胞P53阳性率以及胸腺淋巴细胞FasL阳性率均无增龄变化特性。
4.在腔上囊中,滤泡皮质和髓质淋巴细胞bcl-2mRNA阳性率仅在胚胎期与其Bcl-2蛋白阳性率的变化规律呈一致性;在胚胎及胚后发育过程中,滤泡皮质和髓质淋巴细胞bax mRNA阳性率与其蛋白阳性率的变化规律相同(滤泡髓质20～29周龄除外);两种基因与其蛋白的组织分布不同,其表达存在转录后调控。在胸腺胚胎及胚后发育过程中,皮质和髓质淋巴细胞bcl-2和bax mRNA阳性率均与其蛋白阳性率的变化规律相似;两种基因与其蛋白的组织分布一致,其表达涉及转录水平调控。
5.CGRP、VIP、SP、NPY、SS神经肽阳性细胞在腔上囊和胸腺中广泛分布,它们在两种免疫器官中的首次发生时间不同,其数量呈现一定的增龄变化规律。胸腺胚后发育过程中存在CGRP、VIP、SP、NPY肽能神经支配,优势分布于胸腺髓质。腔上囊中存在VIP神经纤维。腔上囊的FAE以及胸腺的胸腺小体和上皮细胞囊均可表达上述神经肽。
本试验结果表明:在胚胎及胚后发育过程中,天府肉鸭腔上囊和胸腺的形态组织结构、细胞增殖与凋亡、凋亡蛋白与基因以及神经肽的表达表现出明显的增龄变化特性。两种免疫器官通过细胞增殖、凋亡以及神经肽的表达共同调节T、B淋巴细胞的增殖、分化和成熟,参与鸭中枢免疫器官发育和退化的调控。Caspase-3、Bcl-2、Bax、Fas、FasL、P53凋亡蛋白及其bcl-2和baxmRNA凋亡基因的表达直接调控腔上囊和胸腺淋巴细胞的凋亡。本研究从多角度和多层次首次揭示了天府肉鸭中枢免疫器官发生、发育及退化的变化规律及调控机制,将为调节其免疫器官发育和稳定,制定合理的免疫程序提供理论依据。
In this study ,150 Tianfu ducks were divided into 30 groups as follows: 17 groups in the embryonic period (one group per day from 12 to 28 days embryonic stage), 13 groups after hatching(0、1、3、5、8、11、14、17、20、23、26、29、32 weeks) . Using morphological method, light and electron microscopy, immunohistochemisty, terminal deoxynucleotidyl transferase biotin-dUTP nick end labelling (TUNEL) and in sita hybridization techniques, the morphological structures, cell proliferation and apoptosis, apoptotic proteins and genes and neuropeptide expression during the embryonic and post embryonic development of the central immune organs of Tianfu duck were studied. All results are shown as follows:
1. The morphological and histological structures of the duck bursa of Fabricius and thymus underwent obvious age-related changes during the embryonic and post embryonic development. The post embryonic development of these organs was divided into three stages as follows: the continuous development period (from 0 to 8 weeks), the matured and sustained period (in the bursa: from 8 to 14 weeks; in the thymus: from 8 to 17 weeks) and the regressive period (in the bursa: from 17 to 32 weeks; in the thymus: from 20 to 32 weeks).At 26 days embryonic stage(ES), the bursa and thymus had almost possessed the matured histological structure. The bursa and thymus grew very rapidly from 1 to 3 weeks and 3 to 5 weeks after hatching (AH), respectively, and gained their maximum in size and absolute weight at 8 weeks AH. The growth of bursal follicle associated epithelium (FAE),taking part in the post embryonic growth of the follicle cortex and being related to the bursal regression, showed age-related changes during the post embryonic development. The thymic corpuscle and epithelial cyst, with the latter outnumbering the former and presenting several features, were important functional components of the thymic matrix in the duck thymus. The bursa of Fabricius regressed earlier and more quickly than the thymus.
2. In the bursa, the apoptosis ratios of lymphocytes in the follicle cortex followed a series of changes as rising (from 22 days ES to neonatal stage), dropping (from 3 to 5 weeks AH) and maintaining at a certain level (from 0 to 3 weeks and from 5 to 14 weeks AH), and increasing again(from 14 to 29 weeks AH). Increasing from 1 to 3 weeks AH, the changing pattern of the apoptosis ratios of lymphocytes in the follicle medullar in other groups was similar to those in the follicle cortex. The apoptosis ratios of busal lymphocytes in the medullar were significantly higher from 22 days ES to 14 weeks AH or lower from 17 to 29 weeks AH than those in the cortex. The apoptosis ratios of thymic lymphocytes in the cortex and medullar kept unchanged (from 22 to 26 days ES and from 8 to 17 weeks AH) and increased (from 26 days ES to 8 weeks AH, and from 17 to 32 weeks AH).In each group, the apoptosis ratios of thymic lymphocytes in the cortex were significantly higher than those in the medullar. The ultrastructure and process of lymphocytes apoptosis in the bursa were similar to those in the thymus. The nuclei of apoptotic lymphocytes with great changes presented different features. In the bursa, the proliferative indexes of lymphocytes in the follicle cortex and medullar increased during the embryonic development and decreased during the post embryonic development. Moreover, the proliferative indexes of bursal lymphocytes in the medullar were significantly higher than those in the cortex in each group. In the thymus, the proliferative indexes of lymphocytes in the cortex and medullar decreased during both the embryonic and post embryonic development. The proliferative indexes of thymic lymphocytes in the cortex were significantly higher than those in the medullar in each group.
3.In the bursa, the Bcl-2 positive ratios and the ratios of Bcl-2 and Bax of lymphocytes in the follicle cortex and medullar paralleled reversely with the apoptosis ratios of lymphocytes (except 26 days ES to 14 weeks AH and from 5 to 14 weeks AH in the follicle cortex, and from 5 to 14 weeks AH in the follicle medullar ). The Caspase-3, Bax, Fas and FasL positive ratios of lymphocytes in the follicle cortex and medullar paralleled positively with the apoptosis ratios of lymphocytes (except Bax positive ratios from 22 days ES to 5 weeks AH). Furthermore, the ratios of Bcl-2 and Bax of lymphocytes in the follicle cortex were significantly higher from 22 days ES to 14 weeks AH, and lower from 17 to 29 weeks than those in the follicle medullar, which paralleled reversely with the apoptosis indexes of lymphocytes in the follicle cortex and medullar. The positive ratios of Caspase-3, Fas and FasL of bursal lymphocytes in the follicle cortex were significantly lower from 22 days ES to 14 weeks AH, and higher from 17 to 29 weeks AH than those in the medullar, which paralleled positively with the apoptosis ratios of lymphocytes in the follicle cortex and medullar. In the thymus, the ratios of Bcl-2 and Bax of lymphocytes in the cortex and medullar paralleled reversely with the apoptosis ratios of lymphocytes from 26 days ES to 8 weeks AH and from 20 to 32 weeks AH. The Bcl-2 positive ratios of lymphocytes in the thymic cortex and medullar paralleled reversely with the apoptosis ratios of lymphocytes from 20 to 32 weeks AH. The positive ratios of Caspase-3 ,Bax and Fas of lymphocytes in the thymic cortex and medullar paralleled positively with the apoptosis indexes of lymphocytes(except Fas positive ratios from 3 to 8 weeks AH).The ratios of Bcl-2 and Bax, the positive ratios of Caspase-3 and Fas of thymic lymphocytes in the cortex were significantly lower or higher than those in the medullar in each group which paralleled reversely or positively with the apoptosis ratios of lymphocytes in the cortex and medullar, respectively. The P53 positive ratios of lymphocytes in the bursa and thymus showed no age-related changes during the embryonic and post embryonic development, so did the FasL positive ratios of lymphocytes in the thymus.
4. Only during embryonic development of the bursa did the change patterns of the positive ratios of bcl-2 mRNA of lymphocytes in the follicle cortex and medullar parallel positively with those of the positive ratios of Bcl-2 proteins. During the embryonic and post embryonic development of the bursa, the change patterns of the positive ratios of bax mRNA of lymphocytes in the follicle cortex and medullar were similar to those of the positive ratios of Bax proteins (except 20 to 29 weeks AH in the medullar). bcl-2 and bax mRNA in the bursa were different from those of their proteins in the tissue distribution, whose expression presented the regulative mechanism after transcription. During the embryonic and post embryonic development of the thymus, the bcl-2 and bax mRNA of lymphocytes in the thymic cortex and medullar were similar to those of the positive ratios of Bcl-2 and Bax proteins both in the changing pattern of their positive ratios and in their tissue distribution, whose expression appeared to be modulated transcriptionally.
5. The first expression being different, CGRP, VIP, SP, NPY, SS positive cells whose number underwent certain age-related changes were widely located in the bursa and thymus. CGRP, VIP, SP, NPY positive nerves with predominant distribution in the medullar region were occurred in the thymus during the post embryonic development. Only the VIP positive nerves were observed in the bursa. CGRP, VIP, SP, NPY, SS expressions were detected in the bursal FAE and the thymic corpuscles and epithelial cysts.
Based on the results mentioned above, it shows that the morphological and histological structures, cell proliferation and apoptosis, apoptotic proteins and genes and neuropeptide expression in the central immune organs of Tianfu duck undergo obvious age-related changes during the embryonic and post embryonic development. The cell proliferation, apoptosis and neuropeptide expression in these organs supervise and control the proliferation and differentiation of T, B lymphocytes cooperatively, which plays significant and regulatory roles in the development and regression of the duck central immune organs. Caspase-3, Bcl-2, Bax, Fas, FasL and P53 apoptotic proteins and bcl-2 and bax mRNA genes modulate the apoptosis of lymphocytes in the bursa and thymus. The changing patterns and regulatory mechanism of the whole development and regression of the central immune organs of Tianfu duck are studied systematically for the first time, which might provide the theoretical evidences for the modulation of their development and stabilization and formulation of the reasonable immune procedures.
引文
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