大剂量地塞米松对SAP肺损伤的治疗作用

Treatment of lung injury in severe (acute) pancreatitis with large do sage of dexamethsone in rats

目的:探讨大剂量地塞米松对重症急性胰腺炎(SAP)肺损伤的治疗机制及作用.方法:建立SD大鼠急性胰腺炎模型,随机分为对照组、SAP组及地塞米松治疗组.取肺组织行组织病理观察、组织含水量、微血管通透性及肺髓过氧化物酶(MPO)活性检测,同时检测肺组织中血管内皮细胞凋亡及TNF-α,ICAM-1基因表达.结果:SAP组大鼠微血管内大量白细胞浸润,肺组织血管内皮细胞凋亡增加;治疗组肺间质水肿及白细胞浸润程度均较SAP组减轻,微血管内皮细胞数量明显减少.SAP组与对照组相比,肺组织含水量、微血管通透性、MPO活性及TNF-α,ICAM-1基因表达均明显升高,地塞米松治疗组上述指标均较SAP组明显好转(P<0.01).结论:大剂量地塞米松可通过抑制炎症介质、改善血管内皮细胞的功能损伤、降低肺组织血管通透性等作用治疗SAP肺损伤.

AIM： To investigate the pathogenesis and action of large dosage of dexamethsone on lung injury in severe acute pancreatitis （SAP）. METHODS： SD rats with sodium taurocholate-induced SAP were randomly divided into 3 groups： control group, SAP group and dexamethsone group. Lung tissues were obtained for pathological study and dry/wet ratio, microvascular permeability and myeloperocidase （MPO） activity were detected. Apoptosis of endothelial cells and gene expression of TNF-α and ICAM-1 in lung tissue were detected. RESULTS： After inducing SAP model, a great quantity of PMNs were present in capillaries and apoptosis degree of blood vessel endothelium also increased. The degree of PMNs infiltration and apoptosis of endothelium decreased in dexamethasone group. Compared with those in control group, the dry/wet ratio, microvascular permeability, MPO activity and gene expression of TNF-α and ICAM-1 in lung tissue obviously increased. In dexamethasone group, the above indices correspondingly decreased （ P 〈 0.01 ）. CONCLUSION： Large dosage of dexamethsone can ameliorate lung injury by inhibiting inflammatory mediators, alleviating functional injury of endothelial cells and decreasing capillary permeability of lung tissues in SAP.