Jiang L, He L, Qu J
Department of Pulmonology, ZhongShan Hospital, Shanghai Medical University.
Zhonghua Jie He He Hu Xi Za Zhi. 1996 Jun;19(3):143-6.
To investigate the pulmonary inflammatory response and TNF-mediated effects in ICH.
ICH models of guinea pigs were induced successfully by receiving daily intraperitoneal injections of cyclophosphamide (15mg.kg-1.d-1) plus daily subcutaneous injection of cortisone acetate (100mg.kg-1.d-1) for a total of 7 consecutive days. On the day after the final dose of drugs, guinea pigs were challenged intratracheally with LPS (200 micrograms/animal) and were lavaged before and 1, 3, 5, 8, 24 hours after challenged, respectively.
Five hours after LPS challenged, total counts of bronchoalveolar fluid (BALF) cells and the proportion of PMN increased significantly. Although the counts of both PAM and PMN increased, the proportion of PAM decreased gradually accompanied by increase of the proportion of PMNs. Hematoxylin eosin stained lung sections after challenged with LPS showed an acute intraalveolar inflammatory response. After intra-tracheal injection of LPS, the TNF level in BALF progressively increased. Both the TNF level and PMN count started to increase at 1 hour after LPS challenge, peaked at 5 hours. The TNF level in serum did not increase markedly after intratracheal injection of LPS. In the development of an inflammatory response, a large amount of TNF were released in BALF, the level of TNF in BALF was closely matched the influx of PMN.
The data suggested that TNF was one of the cytokines which mediated influx of PMNs and inflammation. High level of TNF released in BALF of ICH could induce the lung injury. The systemic inflammatory response of ICH was involving immunosuppressed state after intratracheal injection of LPS, however, strong intraalveolar inflammatory response still occurred, which reflected the phenomenon of "compartmentalization" in inflammatory response.
研究脑出血（ICH）中的肺部炎症反应及肿瘤坏死因子（TNF）介导的效应。
通过连续7天每日腹腔注射环磷酰胺（15mg·kg⁻¹·d⁻¹）加每日皮下注射醋酸可的松（100mg·kg⁻¹·d⁻¹）成功诱导豚鼠脑出血模型。在末次给药后一天，豚鼠经气管内给予脂多糖（LPS，200微克/只动物），并分别在给药前及给药后1、3、5、8、24小时进行灌洗。
LPS攻击后5小时，支气管肺泡灌洗液（BALF）细胞总数及中性粒细胞比例显著增加。虽然肺泡巨噬细胞（PAM）和中性粒细胞数量均增加，但PAM比例逐渐下降，同时中性粒细胞比例增加。LPS攻击后苏木精-伊红染色的肺切片显示肺泡内急性炎症反应。气管内注射LPS后，BALF中TNF水平逐渐升高。TNF水平和中性粒细胞计数在LPS攻击后1小时开始升高，5小时达到峰值。气管内注射LPS后血清中TNF水平无明显升高。在炎症反应发展过程中，BALF中释放大量TNF，BALF中TNF水平与中性粒细胞流入密切相关。
数据表明TNF是介导中性粒细胞流入和炎症的细胞因子之一。脑出血患者BALF中释放的高水平TNF可诱导肺损伤。脑出血的全身炎症反应在气管内注射LPS后处于免疫抑制状态，但仍发生强烈的肺泡内炎症反应，这反映了炎症反应中的“分隔化”现象。
