Johanson W G, Pierce A K
J Clin Invest. 1973 Nov;52(11):2921-7. doi: 10.1172/JCI107488.
Intrapulmonary deposition of the proteolytic enzyme papain produces a lesion resembling emphysema in experimental animals. The natural history of this lesion has not been well defined. The present study was performed to evaluate changes in lung structure and function with aging in normal rats and rats exposed to an aerosol of papain at 2 mo of age. Groups of control and papain-exposed animals were studied at 4, 8, and 18 mo of age. The parameters of lung function studied were specific airways' conductance (G(aw)/TGV), diffusing capacity per unit of alveolar volume (D(Lco)/V(A)), diffusing capacity (D(Lco)), and functional residual capacity (FRC). Morphometric parameters were the postfixation lung volume (V(L)) and mean chord length (L(M)); internal surface area (ISA) and ISA extrapolated to both the mean V(L) of the corresponding papain group and a V(L) of 10 ml (ISA(10)) were calculated. At 4 mo of age L(M) and FRC were significantly increased and ISA, D(Lco)/V(A), and D(Lco) were significantly reduced in the papain group. At 8 mo of age L(M) was significantly increased and ISA was significantly decreased in the papain group: physiologic studies were not performed in this group. At 18 mo of age L(M) was significantly increased and D(Lco)/V(A), D(Lco), and ISA were significantly decreased. Neither progression nor healing of the lesion was observed despite similar lung growth in both groups. This study demonstrates that a single proteolytic lung injury produces a fixed deficit of lung parenchyma. Progressive lung destruction may require repeated or continuous lung injury.
蛋白水解酶木瓜蛋白酶在实验动物肺内沉积会产生类似肺气肿的病变。这种病变的自然病程尚未明确界定。本研究旨在评估正常大鼠以及2月龄时暴露于木瓜蛋白酶气雾剂的大鼠随着年龄增长肺结构和功能的变化。对对照组和暴露于木瓜蛋白酶的动物组在4、8和18月龄时进行研究。所研究的肺功能参数包括比气道传导率(G(aw)/TGV)、单位肺泡容积的弥散量(D(Lco)/V(A))、弥散量(D(Lco))和功能残气量(FRC)。形态学参数为固定后肺容积(V(L))和平均弦长(L(M));计算内表面积(ISA)以及外推至相应木瓜蛋白酶组平均V(L)和10 ml的V(L)时的ISA(ISA(10))。在4月龄时,木瓜蛋白酶组的L(M)和FRC显著增加,而ISA、D(Lco)/V(A)和D(Lco)显著降低。在8月龄时,木瓜蛋白酶组L(M)显著增加,ISA显著降低:该组未进行生理学研究。在18月龄时,L(M)显著增加,D(Lco)/V(A)、D(Lco)和ISA显著降低。尽管两组肺生长相似,但未观察到病变的进展或愈合。本研究表明,单次蛋白水解性肺损伤会导致肺实质的固定性缺陷。进行性肺破坏可能需要反复或持续的肺损伤。