Prior M, Green F, Lopez A, Balu A, De Sanctis G T, Fick G
Animal Sciences, Alberta Environmental Centre, Vegreville, Canada.
Toxicol Pathol. 1990;18(2):279-88. doi: 10.1177/019262339001800206.
One of the major target organs of hydrogen sulphide gas is the lung. Exfoliation of upper respiratory epithelia and pulmonary edema are prominent effects. Various neuropeptides contained in afferent C-fibres are intimately associated with the epithelia of the conducting airways and are liberated upon exposure to noxious gases. We sought to determine their role in the pathogenesis of hydrogen-sulphide-induced pulmonary injury by pretreating rats with the neurotoxin, capsaicin, which is known to ablate a subpopulation of vagal afferent C-fibres. Groups of capsaicin and saline (control) pretreated Fischer 344 rats were exposed to an edemogenic concentration of hydrogen sulphide (525-559 mg/m3) for 4 hr. Mortality was significantly greater (p less than 0.01) in the capsaicin treated rats (12/12) compared to the control animals (2/12). Pulmonary injury was also more severe in the capsaicin pretreated animals as assessed by lung water content, histological grade of pulmonary edema and protein in the broncho-alveolar fluid. Animals depleted of substance P exhibited a significantly greater (p less than 0.01) degree of bronchial epithelial cell exfoliation and ulceration following exposure to hydrogen sulphide. These experiments indicate that capsaicin sensitive sensory nerves may play a major role in pulmonary defense against the effects of inhaled toxic gases such as hydrogen sulphide.
硫化氢气体的主要靶器官之一是肺。上呼吸道上皮脱落和肺水肿是其显著影响。传入C纤维中含有的各种神经肽与传导气道的上皮密切相关,并在接触有害气体时释放出来。我们试图通过用神经毒素辣椒素预处理大鼠来确定它们在硫化氢诱导的肺损伤发病机制中的作用,已知辣椒素会消除一部分迷走神经传入C纤维。将辣椒素预处理组和生理盐水(对照组)预处理的Fischer 344大鼠暴露于致水肿浓度的硫化氢(525 - 559 mg/m³)中4小时。与对照动物(2/12)相比,辣椒素处理的大鼠(12/12)死亡率显著更高(p < 0.01)。通过肺含水量、肺水肿组织学分级和支气管肺泡灌洗液中的蛋白质评估,辣椒素预处理动物的肺损伤也更严重。暴露于硫化氢后,P物质耗竭的动物支气管上皮细胞脱落和溃疡程度显著更高(p < 0.01)。这些实验表明,辣椒素敏感的感觉神经可能在肺部抵御吸入有毒气体(如硫化氢)的影响中起主要作用。