Carver T W, Srinathan S K, Velloff C R, Pérez Fontán J J
The Edward Mallinckrodt Department of Pediatrics, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Am J Respir Cell Mol Biol. 1997 Dec;17(6):691-701. doi: 10.1165/ajrcmb.17.6.2830.
To test the hypothesis that increased airway strain resulting from lung denervation initiates a fibroproliferative response in the airways, we compared the transcriptional expressions of alpha1(I)-procollagen and tropoelastin in the lungs of rats subjected to unilateral vagal denervation, unilateral vagal denervation combined with ipsilateral phrenectomy, or thoracotomy without denervation (controls). We found increases in alpha1(I)-procollagen messenger ribonucleic acids (mRNAs) in the submucosa of the airways and the adventitia of airways and pulmonary vessels of the denervated lungs in 31% of the rats subjected to unilateral denervation (with and without phrenectomy), and in none of the controls. The increased transcripts were associated with collagen deposition in the peribronchial and perivascular tissue, and occasionally with cell proliferation leading to occlusion of the airway and vascular lumina. Unilateral phrenectomy did not decrease the frequency with which production of Type I procollagen was upregulated, suggesting that the upregulation was not entirely dependent on airway strain. Tropoelastin expression was not influenced by denervation. Our results indicate that the autonomic nervous system has a previously unsuspected trophic influence on collagen synthesis in the airways and pulmonary vessels. Abolition of this influence by denervation may lead to structural changes analogous to those observed in bronchiolitis obliterans after lung transplantation.
为了验证因肺去神经支配导致气道应变增加会引发气道内纤维增生反应这一假说，我们比较了接受单侧迷走神经切断术、单侧迷走神经切断术联合同侧膈神经切除术或开胸但未去神经支配（对照组）的大鼠肺组织中α1（I）-前胶原和原弹性蛋白的转录表达。我们发现，在接受单侧去神经支配（无论是否进行膈神经切除术）的大鼠中，31%的大鼠去神经支配肺组织的气道黏膜下层以及气道和肺血管外膜中的α1（I）-前胶原信使核糖核酸（mRNA）增加，而对照组中无一例出现这种情况。转录本增加与支气管周围和血管周围组织中的胶原沉积有关，偶尔还与导致气道和血管腔闭塞的细胞增殖有关。单侧膈神经切除术并未降低I型前胶原产生上调的频率，这表明这种上调并不完全依赖于气道应变。原弹性蛋白表达不受去神经支配的影响。我们的结果表明，自主神经系统对气道和肺血管中的胶原合成具有此前未被怀疑的营养性影响。去神经支配消除这种影响可能会导致类似于肺移植后闭塞性细支气管炎中观察到的结构变化。
