内毒素休克猕猴肺内血小板衍生因子和溶酶体变化

Effect of platelet-derived growth factor and lysosomes of lung injury in macaque with early-phase endotoxic shock

目的研究猕猴在内毒素休克前后血气变化,肺的超微结构、溶酶体的变化、肺泡内血小板衍生长因子(PDGF)免疫组化的表现,探讨其在肺损伤中的意义。方法猕猴11只,6只为内毒素组,制成内毒素休克模型,分别在内毒素攻击前、攻击60 min、攻击120 min时采血,检测血气;5只为对照组,也在相应时点采血。内毒素组120 min时杀死动物,取肺组织做超微结构、电镜酸性磷酸酶细胞组织化学、PDGF免疫组化检测。结果内毒素组及对照组在内毒素攻击前、攻击60 min、120 min时气体交换指数无变化。内毒素组动物肺泡内见呼吸上皮、基底膜、血管内皮细胞损伤,细胞内溶酶体数量增多、破坏,PDGF阳性蛋白在肺泡间隔上沉积;而对照组动物肺泡内及血管内皮未见PDGF阳性染色、呼吸上皮和血管内皮无损伤,溶酶体结构正常。结论休克早期就有了肺部的损害,PDGF可能参与了早期肺组织损伤过程;而此损伤未影响换气指数变化。

Objective To study the effect of platelet-derived growth factor （PDGF） and lysosomes on lung injury in macaque with early-phase endotoxic shock. Method Eleven macaques were randomly divided into two groups, namely, control group （Co group, n = 5） and endotoxic group （En group, n = 6）. The macaque of the Co group injected with 1 ml/kg normal saline and the macque of the En group received a dose of 2.8 mg/kg Lipopolysaccharides （LPS） i. v. The blood gas was detected at 120 minutes after LPS challenging. Uhrastructure, cytochemistry of acid phosphatase （ACPase） detection by electronic microscopy and immunohistochemical assay of PDGF were completed in lungs of all the macaque . Results Administration of LPS did not change the parameters of gas exchange, namely, PaO2, PaO2/Fi and PaCO2. In the early phase of endotoxic shock, ACPase activity products increased and lysosome destroyed in the alveolar cells. The pathologic changes of alveolus, such as degeneration of vessel endothehum, injmy of alveolar epithehum and damage of basement membrane, and transudation of blood component were observed by electron microscopy in the En group. However, no pathological changes were found in the control group. By immunohistochemical staining, PDGF on alveolar wall in the En animals was observed, whereas no PDGF protein in the Co macaques was noticed. Conclusions Administration of LPS induced the expression of PDGF in the alveolar wall and lysosome injmy in the alveolar ceils, as a result of alveolar damage in early-phase endotoxin shock. In the meantime, the parameters of gas exchanges did not change. The PDGF may play an important role in the pathogenesis of lung during the early-phase of endotoxin shock.