去神经支配后对鼠肺神经内分泌细胞影响的实验研究
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摘要
肺神经内分泌细胞(PNEC)系统是由单个PNEC及成簇的PNEC形成的神经上皮小体(NEB)组成。已知PNEC具有气道氧化学感受器,调节气道反应性,促进肺的生长发育的功能。近来还发现PNEC可作为气道上皮干细胞促进肺损伤后修复,PNEC与小细胞肺癌密切相关。这些功能的发挥主要通过迷走神经节的感觉传入神经纤维支配。
NEB中存在双重感觉神经纤维支配。一是由迷走神经结状神经节的钙结合蛋白D28K和P2X3受体免疫神经纤维组成的感觉神经纤维;另一是由背根神经节的P物质和降钙素基因相关肽(CGRP)免疫反应性神经纤维组成。CGRP在神经节中合成后随之被转运到神经末梢,通过迷走神经传入神经元调节其行为。从气道近端至远端双重感觉神经纤维的密度逐渐降低直至单个神经纤维穿过气道上皮及上皮下层,单个PNEC及NEB可能通过粘膜下层的微细神经纤维相互连接。单侧迷走神经切断后会出现同侧的神经末梢退化或消失,PNEC及NEB也可能会出现相应改变。
临床在气管、支气管成形术及肺移植过程中,由于切断了支配支气管粘膜及肌肉的神经纤维,去神经支配后肺神经内分泌细胞的数量、分布及神经活性物质分泌功能的改变;PNEC对于神经刺激的应答,PNEC产生的神经免疫、神经内分泌的功能,以及这些改变对于气管、支气管粘膜的修复有何影响?目前尚不清楚。因此,研究去神经支配后肺神经内分泌细胞数量、分布及神经活性物质的分泌功能的改变,具有十分重要的意义。
研究目的
通过切断鼠单侧迷走神经和支气管重建观察去神经后PNEC和NEB的数量、形态结构及其分泌神经活性物质的变化,以探讨PNEC的功能及其在气道损伤及修复中的作用。
实验方法
1.30只SD大鼠切断左侧迷走神经,术后按取样时间随机分为术后一周、一月、三月组,每组10只;另设10只正常SD大鼠作为对照组。电镜观察肺神经内分泌细胞的超微结构;采用Grimelius银染色法观察肺神经内分泌细胞数量及分布;免疫组化法检测五羟色胺阳性神经内分泌细胞、降钙素基因相关肽阳性神经内分泌细胞的表达;采用放射免疫分析法测定血清中CGRP浓度;RT-PCR法测定肺组织CGRP mRNA表达。
2.30只SD大鼠左侧支气管重建术,术后按取样时间随机分为术后一周、一月、三月组,每组10只;另设10只正常SD大鼠作为对照组。HE切片观察支气管重建术后支气管愈合情况;采用Grimelius银染色法观察肺神经内分泌细胞数量及分布;免疫组化法检测五羟色胺阳性神经内分泌细胞、降钙素基因相关肽阳性神经内分泌细胞的表达;采用放射免疫分析法测定血清中CGRP浓度;RT-PCR法测定肺组织CGRP mRNA表达。
实验结果
1.PNEC超微结构:电镜下见PNEC分布于肺内支气管和细支气管上皮内,PNEC呈烧瓶样、卵圆形和锥型,细胞从上皮基底膜延伸至支气管管腔或者沿基底膜在相邻气道上皮间伸展,顶端狭窄形成尖形突起抵达管腔,有些细胞顶端靠近腔面处常有短微绒毛。在细胞浆中富含具有特征性的致密核心小泡(DCV),一般呈球状,直径约70～200nm,外被单位膜,内含电子高密度的核心,核心和膜之间有一薄的光晕。PNEC内可见数量不等的游离核蛋白体、光面内质网与粗面内质网、成束的微丝和线粒体,线粒体较相邻细胞的更小,高尔基体位于细胞核靠上处。
2.迷走神经切断术后一周和一月Grimelius银染色见神经内分泌细胞多位于肺内支气管上皮,其数量大幅度增加,且有多个神经内分泌细胞聚集形成神经上皮小体;至三月接近正常对照组;进一步免疫组化检测见迷走神经切断术后一周、一月大支气管内5-HT、CGRP阳性PNEC和NEB数量大量增加(P﹤0.01),至术后三月时接近正常对照组(P﹥0.05)。小支气管、周围细支气管内5-HT、CGRP阳性PNEC和NEB数量无显著差异(P﹥0.05)。
3.迷走神经切断术后一周和一月血清CGRP含量比正常对照组显著降低(P﹤0.01),随着时间延长,血清中CGRP含量逐渐增加,至三月时接近正常对照组;而肺组织CGRP mRNA表达在术后一周和一月均明显高于对照组(P﹤0.01),随着时间的延长,其表达量逐渐减少,至术后三月时接近正常对照组(P﹥0.05)。
4.支气管重建术后支气管吻合口肉芽组织增生,可见支气管粘膜中断,内皮细胞增生形成的实性细胞索及扩张的毛细血管,毛细血管周围可见大量的纤维母细胞及炎性细胞。
5.支气管重建术后一周和一月Grimelius银染色见神经内分泌细胞多位于肺内支气管上皮,其数量大幅度增加,且有多个神经内分泌细胞聚集形成神经上皮小体;至三月接近正常对照组;进一步免疫组化检测见支气管重建术后一周、一月大支气管内5-HT、CGRP阳性PNEC和NEB数量大量增加(P﹤0.01),至术后三月时接近正常对照组(P﹥0.05)。小支气管、周围细支气管内5-HT、CGRP阳性PNEC和NEB数量无显著差异(P﹥0.05)。
6.支气管重建术后一周和一月血清CGRP含量比正常对照组显著降低(P﹤0.01),随着时间延长,血清中CGRP含量逐渐增加,至三月时接近正常对照组;而肺组织CGRP mRNA表达在术后一周和一月均明显高于对照组(P﹤0.01),随着时间的延长,其表达量逐渐减少,至术后三月时接近正常对照组(P﹥0.05)。
结论
1.神经内分泌细胞的超微结构特征——细胞浆中致密核心小泡(DCV)可作为PNEC特征性标志。
2.迷走神经切断后可明显影响肺神经内分泌细胞数量、分布及神经活性物质的分泌,从而表明迷走神经具有支配、调节肺神经内分泌细胞分化及分泌神经活性物质的功能。
3.迷走神经切断后血清内CGRP浓度下降及肺内CGRP mRNA表达量增加之变化,表明迷走神经对CGRP基因的表达和神经活性物质CGRP的分泌具有调节作用。
4.支气管重建术后PNEC的数量增加及5-HT,CGRP阳性PNEC和NEB大量增生,一方面表明PNEC受其支配的神经纤维调节,另一方面表明PNEC可能参与了气道的损伤与修复。
5.支气管重建术后近期血清内CGRP浓度下降及肺内CGRP mRNA表达量增加之变化,表明肺内CGRP-IR神经纤维调节CGRP基因的表达和神经活性物质CGRP的分泌;推测CGRP具有局部调节因子刺激内皮细胞增生,参与了气道的损伤与修复。
The pulmonary neuroendocrine cells (PNEC) system consists of solitary cells and distinctive cell clusteres termed neuroepithelial bodies (NEB). The pulmonary neuroendocrine system is still regarded as an oxygen sensitive chemoreceptor with local and reflex-mediated regulatory functions, and as a regulator of airway reactivity, and as a regulator of lung growth and development. A novel role of PNEC or NEB is emerging as guardians of lung stem cell niches. This has potential implications for carcinogenesis and injury repair. These functions are always played a part in afferent sensory fibers of vagal originating with cell bodies residing in the nodose ganglion.
NEB is under dual sensory innervation. A vagal sensory component with origin in the nodose ganglion revealed calbinding D28K and P2X3 purinoreceptor immunoreactive nerve fibers that were myelinated. Another sensory nerve fiber system is consisted of thin unmyelinated, nonvagal substance P/CGRP immunoreactive nerves that have their origin in dorsal root ganglia. CGRP was synthetized in neural ganglion and transported to nerve ending, the secretion of CGRP was regulated afferent neuron of vagus. There is a decreasing nerve density from proximal to more distal conducting airways, while there remains a frequent interchange of single nerve fibers across epithelial and subepithelial compartments without termination. NEB and solitary PNEC may be actually interconnected via fine submucosal nerve fibers. Unilateral vagotomy led to degeneration and disappearance of ipsilateral NEB,and NEB and solitary PNEC may be changed.
The nerve fiber of broncho-mucosa and muscles would be cut in the process of tracheoplasty, bronchoplasty and lung transplantation in clinic. The response of neurostimulation would be changed, likewise neuro-immunity and the function of neuroendocine. These changes would be bought about extremely significant effect in the process of trachea-mucosal and broncho-mucosal repair. Hence, it will be important to investigate the effects and significance of amount, distribution and their secreting function of pulmonary neuroendocrine cells (PNEC) following denervation.
AIM:
To study the effects and changes of amount, distribution, secretion of pulmonary neuroendocrine cells after vagotomy and reconstruction of bronchus to explore the function of PNEC and the role of PNEC in damage and repair of airway after denervation.
METHODS:
1. 30 male sprague dawley rats were randomly divided into three groups according to sample taking time after left cervical vagotomy:1 week, 1 month, 3 months with 10 animals in each, and another 10 rats without vagotomy were used as normal control. The ultramicrostructure of PNEC were observed with electron microscope. The quantity and distribution of PNEC were studied by Grimelius silver stain. Both serotonin (5-HT) positive PNEC and calcitonin gene-related peptide (CGRP) positive PNEC were studied by immunohistochemistry. The serous concentration of CGRP was detected by radio-immunity analysis method. The level of expression of CGRP mRNA was measured by RT-PCR method.
2. 30 male sprague dawley rats were randomly divided into three groups according to sample taking time after left reconstruction of bronchus: 1 week, 1 month, 3 months with 10 animals in each, and another 10 rats without surgery were taken as normal control. The broncho-healing states were observed with HE staining slice after after left reconstruction of bronchus. The quantity and distribution of PNEC were studied by Grimelius silver stain. Both serotonin (5-HT) positive PNEC and calcitonin gene-related peptide (CGRP) positive PNEC were studied by immunohistochemistry. The serous concentration of CGRP was detected by radio-immunity analysis method. The level of expression of CGRP mRNA was measured by RT-PCR method.
RESULTS:
1. The electron microscopic studies have shown that PNEC were mainly found in the epithelium of trachea, bronchus and bronchioles. The cells are usually flask, oval or pyramidalshaped with most of them concentrated at the lumina of respiratory tract from basal lamina or extended along the lamina of the contiguous epitheliums. Occasionally, the lateral dendriteike cytoplasmic processes extend between adjacent epithelial cells. The apical region of the cell reached the lumen where the microvilli were revealed on surface of some cells. The identification of small, cytoplasmic, generally spherical granules, otherwise known as dense-core vesicles (DCV), has been served as the major ultrastructural characteristic of the PNEC. The appearance of DCV was shown as globular. The diameters of these DCVs can range from 70 to 200 nm. The DCV contain a high electronic density core, there is a thin, electron-lucent zone or“halo”betweem core and membrane. Other ultrastructural characteristics associated with PNEC are variable amounts of free ribosomes,smooth and rough endoplasmic reticulum, bundles of cytoplasmic filaments and mitochondria. The latter are usually smaller than those of adjacent cells. The Golgi apparatus is usually visible and present in a supranuclear position.
2. PNECs were mainly found in the epithelium of intra pulmonary bronchus and terminal bronchioles and some of them were assembled to form into neuroepithelial bodies (NEBs). 1 week and 1month after vagotomy, the number of PNEC was significantly increased in larger bronchi, and nearly approached the lever of normal controls after 3 months later. Except their location in the larger bronchi, the changes of 5-HT and CGRP positive PNECs presented the same as PNEC in number. The NEBs were formed by 5-HT positive PNEC or CGRP positive PNEC also.
3. At 1 week and 1 month after vagotomy, the serous concentration of CGRP was significantly decreased than that in the normal controls (P﹤0.01) and gradually increased nearly to the normal level in 3 months after vagotomy. The expression of CGRP mRNA was significantly higher than that in the normal control at 1 week and 1 month after vagotomy (P﹤0.01) and gradually declined to the normal control after 3 months (P﹥0.05).
4. Light microscopic studies have shown granulation tissue hyperblastosis on broncho-shama after reconstruction of bronchus, discontinued Mucosa of bronchus and stuffed bundles of hyperplasia endothelial cells and expanded blood capillary. There were massive fibroblast and inflammatory cells around blood capillaries.
5. The changes of PNEC and 5-HT and CGRP positive PNECs in number, location, formation of NEB after left reconstruction of bronchus were similar as after vagotomy.
6. At 1 week and 1 month after left reconstruction of bronchus, the serous concentration of CGRP was significantly decreased than that in the normal controls (P﹤0.01) and gradually increased nearly to the normal level in 3 months after left reconstruction of bronchus. The expression of CGRP mRNA was significantly higher than that in the normal control at 1 week and 1 month after left reconstruction of bronchus (P﹤0.01) and gradually declined to the normal control after 3 months (P﹥0.05).
CONCLUSION:
1. DCV has served as the major ultrastructural characteristic of the PNEC.
2. The quantity and distribution and their secreting function of PNEC and 5-HT positive PNEC and CGRP positive PNEC were significantly changed after vagotomy. It indicated that PNEC might be dominated and their secreting function might be regulated by vagus fibres.
3. The serous concentration of CGRP and expression of CGRP mRNA were significantly changed after vagotomy. It indicated that the expression of CGRP mRNA and the secretion of CGRP were dominated and regulated by vagus.
4. The quantity of PNEC and 5-HT positive PNEC and CGRP positive PNEC were significantly increased after reconstruction of bronchus. It indicated that PNEC might be dominated by vagus fibres. Meanwhile, it deduced that PNEC might be taken part in damage and repair of airway.
5. The serous concentration of CGRP and expression of CGRP mRNA were significantly changed after reconstruction of bronchus. It indicated that the expression of CGRP mRNA and the secretion of CGRP were dominated and regulated by CGRP-immunoreactive (IR) fibers of vagus. Meanwhile, it indicated that CGRP was considered as local regulatory factor to stimulate hyperplasia endothelialis and participated in damage and repair of airway.
NEB中存在双重感觉神经纤维支配。一是由迷走神经结状神经节的钙结合蛋白D28K和P2X3受体免疫神经纤维组成的感觉神经纤维;另一是由背根神经节的P物质和降钙素基因相关肽(CGRP)免疫反应性神经纤维组成。CGRP在神经节中合成后随之被转运到神经末梢,通过迷走神经传入神经元调节其行为。从气道近端至远端双重感觉神经纤维的密度逐渐降低直至单个神经纤维穿过气道上皮及上皮下层,单个PNEC及NEB可能通过粘膜下层的微细神经纤维相互连接。单侧迷走神经切断后会出现同侧的神经末梢退化或消失,PNEC及NEB也可能会出现相应改变。
临床在气管、支气管成形术及肺移植过程中,由于切断了支配支气管粘膜及肌肉的神经纤维,去神经支配后肺神经内分泌细胞的数量、分布及神经活性物质分泌功能的改变;PNEC对于神经刺激的应答,PNEC产生的神经免疫、神经内分泌的功能,以及这些改变对于气管、支气管粘膜的修复有何影响?目前尚不清楚。因此,研究去神经支配后肺神经内分泌细胞数量、分布及神经活性物质的分泌功能的改变,具有十分重要的意义。
研究目的
通过切断鼠单侧迷走神经和支气管重建观察去神经后PNEC和NEB的数量、形态结构及其分泌神经活性物质的变化,以探讨PNEC的功能及其在气道损伤及修复中的作用。
实验方法
1.30只SD大鼠切断左侧迷走神经,术后按取样时间随机分为术后一周、一月、三月组,每组10只;另设10只正常SD大鼠作为对照组。电镜观察肺神经内分泌细胞的超微结构;采用Grimelius银染色法观察肺神经内分泌细胞数量及分布;免疫组化法检测五羟色胺阳性神经内分泌细胞、降钙素基因相关肽阳性神经内分泌细胞的表达;采用放射免疫分析法测定血清中CGRP浓度;RT-PCR法测定肺组织CGRP mRNA表达。
2.30只SD大鼠左侧支气管重建术,术后按取样时间随机分为术后一周、一月、三月组,每组10只;另设10只正常SD大鼠作为对照组。HE切片观察支气管重建术后支气管愈合情况;采用Grimelius银染色法观察肺神经内分泌细胞数量及分布;免疫组化法检测五羟色胺阳性神经内分泌细胞、降钙素基因相关肽阳性神经内分泌细胞的表达;采用放射免疫分析法测定血清中CGRP浓度;RT-PCR法测定肺组织CGRP mRNA表达。
实验结果
1.PNEC超微结构:电镜下见PNEC分布于肺内支气管和细支气管上皮内,PNEC呈烧瓶样、卵圆形和锥型,细胞从上皮基底膜延伸至支气管管腔或者沿基底膜在相邻气道上皮间伸展,顶端狭窄形成尖形突起抵达管腔,有些细胞顶端靠近腔面处常有短微绒毛。在细胞浆中富含具有特征性的致密核心小泡(DCV),一般呈球状,直径约70～200nm,外被单位膜,内含电子高密度的核心,核心和膜之间有一薄的光晕。PNEC内可见数量不等的游离核蛋白体、光面内质网与粗面内质网、成束的微丝和线粒体,线粒体较相邻细胞的更小,高尔基体位于细胞核靠上处。
2.迷走神经切断术后一周和一月Grimelius银染色见神经内分泌细胞多位于肺内支气管上皮,其数量大幅度增加,且有多个神经内分泌细胞聚集形成神经上皮小体;至三月接近正常对照组;进一步免疫组化检测见迷走神经切断术后一周、一月大支气管内5-HT、CGRP阳性PNEC和NEB数量大量增加(P﹤0.01),至术后三月时接近正常对照组(P﹥0.05)。小支气管、周围细支气管内5-HT、CGRP阳性PNEC和NEB数量无显著差异(P﹥0.05)。
3.迷走神经切断术后一周和一月血清CGRP含量比正常对照组显著降低(P﹤0.01),随着时间延长,血清中CGRP含量逐渐增加,至三月时接近正常对照组;而肺组织CGRP mRNA表达在术后一周和一月均明显高于对照组(P﹤0.01),随着时间的延长,其表达量逐渐减少,至术后三月时接近正常对照组(P﹥0.05)。
4.支气管重建术后支气管吻合口肉芽组织增生,可见支气管粘膜中断,内皮细胞增生形成的实性细胞索及扩张的毛细血管,毛细血管周围可见大量的纤维母细胞及炎性细胞。
5.支气管重建术后一周和一月Grimelius银染色见神经内分泌细胞多位于肺内支气管上皮,其数量大幅度增加,且有多个神经内分泌细胞聚集形成神经上皮小体;至三月接近正常对照组;进一步免疫组化检测见支气管重建术后一周、一月大支气管内5-HT、CGRP阳性PNEC和NEB数量大量增加(P﹤0.01),至术后三月时接近正常对照组(P﹥0.05)。小支气管、周围细支气管内5-HT、CGRP阳性PNEC和NEB数量无显著差异(P﹥0.05)。
6.支气管重建术后一周和一月血清CGRP含量比正常对照组显著降低(P﹤0.01),随着时间延长,血清中CGRP含量逐渐增加,至三月时接近正常对照组;而肺组织CGRP mRNA表达在术后一周和一月均明显高于对照组(P﹤0.01),随着时间的延长,其表达量逐渐减少,至术后三月时接近正常对照组(P﹥0.05)。
结论
1.神经内分泌细胞的超微结构特征——细胞浆中致密核心小泡(DCV)可作为PNEC特征性标志。
2.迷走神经切断后可明显影响肺神经内分泌细胞数量、分布及神经活性物质的分泌,从而表明迷走神经具有支配、调节肺神经内分泌细胞分化及分泌神经活性物质的功能。
3.迷走神经切断后血清内CGRP浓度下降及肺内CGRP mRNA表达量增加之变化,表明迷走神经对CGRP基因的表达和神经活性物质CGRP的分泌具有调节作用。
4.支气管重建术后PNEC的数量增加及5-HT,CGRP阳性PNEC和NEB大量增生,一方面表明PNEC受其支配的神经纤维调节,另一方面表明PNEC可能参与了气道的损伤与修复。
5.支气管重建术后近期血清内CGRP浓度下降及肺内CGRP mRNA表达量增加之变化,表明肺内CGRP-IR神经纤维调节CGRP基因的表达和神经活性物质CGRP的分泌;推测CGRP具有局部调节因子刺激内皮细胞增生,参与了气道的损伤与修复。
The pulmonary neuroendocrine cells (PNEC) system consists of solitary cells and distinctive cell clusteres termed neuroepithelial bodies (NEB). The pulmonary neuroendocrine system is still regarded as an oxygen sensitive chemoreceptor with local and reflex-mediated regulatory functions, and as a regulator of airway reactivity, and as a regulator of lung growth and development. A novel role of PNEC or NEB is emerging as guardians of lung stem cell niches. This has potential implications for carcinogenesis and injury repair. These functions are always played a part in afferent sensory fibers of vagal originating with cell bodies residing in the nodose ganglion.
NEB is under dual sensory innervation. A vagal sensory component with origin in the nodose ganglion revealed calbinding D28K and P2X3 purinoreceptor immunoreactive nerve fibers that were myelinated. Another sensory nerve fiber system is consisted of thin unmyelinated, nonvagal substance P/CGRP immunoreactive nerves that have their origin in dorsal root ganglia. CGRP was synthetized in neural ganglion and transported to nerve ending, the secretion of CGRP was regulated afferent neuron of vagus. There is a decreasing nerve density from proximal to more distal conducting airways, while there remains a frequent interchange of single nerve fibers across epithelial and subepithelial compartments without termination. NEB and solitary PNEC may be actually interconnected via fine submucosal nerve fibers. Unilateral vagotomy led to degeneration and disappearance of ipsilateral NEB,and NEB and solitary PNEC may be changed.
The nerve fiber of broncho-mucosa and muscles would be cut in the process of tracheoplasty, bronchoplasty and lung transplantation in clinic. The response of neurostimulation would be changed, likewise neuro-immunity and the function of neuroendocine. These changes would be bought about extremely significant effect in the process of trachea-mucosal and broncho-mucosal repair. Hence, it will be important to investigate the effects and significance of amount, distribution and their secreting function of pulmonary neuroendocrine cells (PNEC) following denervation.
AIM:
To study the effects and changes of amount, distribution, secretion of pulmonary neuroendocrine cells after vagotomy and reconstruction of bronchus to explore the function of PNEC and the role of PNEC in damage and repair of airway after denervation.
METHODS:
1. 30 male sprague dawley rats were randomly divided into three groups according to sample taking time after left cervical vagotomy:1 week, 1 month, 3 months with 10 animals in each, and another 10 rats without vagotomy were used as normal control. The ultramicrostructure of PNEC were observed with electron microscope. The quantity and distribution of PNEC were studied by Grimelius silver stain. Both serotonin (5-HT) positive PNEC and calcitonin gene-related peptide (CGRP) positive PNEC were studied by immunohistochemistry. The serous concentration of CGRP was detected by radio-immunity analysis method. The level of expression of CGRP mRNA was measured by RT-PCR method.
2. 30 male sprague dawley rats were randomly divided into three groups according to sample taking time after left reconstruction of bronchus: 1 week, 1 month, 3 months with 10 animals in each, and another 10 rats without surgery were taken as normal control. The broncho-healing states were observed with HE staining slice after after left reconstruction of bronchus. The quantity and distribution of PNEC were studied by Grimelius silver stain. Both serotonin (5-HT) positive PNEC and calcitonin gene-related peptide (CGRP) positive PNEC were studied by immunohistochemistry. The serous concentration of CGRP was detected by radio-immunity analysis method. The level of expression of CGRP mRNA was measured by RT-PCR method.
RESULTS:
1. The electron microscopic studies have shown that PNEC were mainly found in the epithelium of trachea, bronchus and bronchioles. The cells are usually flask, oval or pyramidalshaped with most of them concentrated at the lumina of respiratory tract from basal lamina or extended along the lamina of the contiguous epitheliums. Occasionally, the lateral dendriteike cytoplasmic processes extend between adjacent epithelial cells. The apical region of the cell reached the lumen where the microvilli were revealed on surface of some cells. The identification of small, cytoplasmic, generally spherical granules, otherwise known as dense-core vesicles (DCV), has been served as the major ultrastructural characteristic of the PNEC. The appearance of DCV was shown as globular. The diameters of these DCVs can range from 70 to 200 nm. The DCV contain a high electronic density core, there is a thin, electron-lucent zone or“halo”betweem core and membrane. Other ultrastructural characteristics associated with PNEC are variable amounts of free ribosomes,smooth and rough endoplasmic reticulum, bundles of cytoplasmic filaments and mitochondria. The latter are usually smaller than those of adjacent cells. The Golgi apparatus is usually visible and present in a supranuclear position.
2. PNECs were mainly found in the epithelium of intra pulmonary bronchus and terminal bronchioles and some of them were assembled to form into neuroepithelial bodies (NEBs). 1 week and 1month after vagotomy, the number of PNEC was significantly increased in larger bronchi, and nearly approached the lever of normal controls after 3 months later. Except their location in the larger bronchi, the changes of 5-HT and CGRP positive PNECs presented the same as PNEC in number. The NEBs were formed by 5-HT positive PNEC or CGRP positive PNEC also.
3. At 1 week and 1 month after vagotomy, the serous concentration of CGRP was significantly decreased than that in the normal controls (P﹤0.01) and gradually increased nearly to the normal level in 3 months after vagotomy. The expression of CGRP mRNA was significantly higher than that in the normal control at 1 week and 1 month after vagotomy (P﹤0.01) and gradually declined to the normal control after 3 months (P﹥0.05).
4. Light microscopic studies have shown granulation tissue hyperblastosis on broncho-shama after reconstruction of bronchus, discontinued Mucosa of bronchus and stuffed bundles of hyperplasia endothelial cells and expanded blood capillary. There were massive fibroblast and inflammatory cells around blood capillaries.
5. The changes of PNEC and 5-HT and CGRP positive PNECs in number, location, formation of NEB after left reconstruction of bronchus were similar as after vagotomy.
6. At 1 week and 1 month after left reconstruction of bronchus, the serous concentration of CGRP was significantly decreased than that in the normal controls (P﹤0.01) and gradually increased nearly to the normal level in 3 months after left reconstruction of bronchus. The expression of CGRP mRNA was significantly higher than that in the normal control at 1 week and 1 month after left reconstruction of bronchus (P﹤0.01) and gradually declined to the normal control after 3 months (P﹥0.05).
CONCLUSION:
1. DCV has served as the major ultrastructural characteristic of the PNEC.
2. The quantity and distribution and their secreting function of PNEC and 5-HT positive PNEC and CGRP positive PNEC were significantly changed after vagotomy. It indicated that PNEC might be dominated and their secreting function might be regulated by vagus fibres.
3. The serous concentration of CGRP and expression of CGRP mRNA were significantly changed after vagotomy. It indicated that the expression of CGRP mRNA and the secretion of CGRP were dominated and regulated by vagus.
4. The quantity of PNEC and 5-HT positive PNEC and CGRP positive PNEC were significantly increased after reconstruction of bronchus. It indicated that PNEC might be dominated by vagus fibres. Meanwhile, it deduced that PNEC might be taken part in damage and repair of airway.
5. The serous concentration of CGRP and expression of CGRP mRNA were significantly changed after reconstruction of bronchus. It indicated that the expression of CGRP mRNA and the secretion of CGRP were dominated and regulated by CGRP-immunoreactive (IR) fibers of vagus. Meanwhile, it indicated that CGRP was considered as local regulatory factor to stimulate hyperplasia endothelialis and participated in damage and repair of airway.
引文
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