The Study On Protective Effects Of Liposomal Clodronate On Lung Injury In Severe Acute Pancteatitis

Objective:The aim of this study was to investigate the effect of liposomal clodronate on the expression of protein kinase B(protein kinase B, Akt) and mitogen-activated protein kinase(extracellular regulated protein kinases1/2) [MAPK(ERK1/2)] in the lung of rats with severe acute pancreatitis(SAP), and to study the therapeutic effect of liposomal clodronate on SAP-associated lung injury.Method:Liposomal clodronate was prepared by using thin film method. 48 SD rats were randomly divided into a sham group, a SAP+ blank liposome group(SAP group), a SAP+ liposomal clodronate(LC group). The models of sham group were injected with the same amount of 0.9% physiological saline solution. The models of SAP group and LC group were established by injection of 5% sodium taurocholate into the pancreatic capsule. Serum levels of interleukin-6(IL-6),tumor necrosis of factor-α(TNF-α),amylase(AMS) and myeloperoxidase(MPO) in lung tissue were measured 2 and 6 h after SAP induction. Pathological of pancreas and lung tissue were observed. The expression of Akt and MAPK(ERK) in lung tissue was detected by immunohistochemistry.Result:Compared with sham group, the serum levels of AMS in SAP group were increased significantly(P < 0.01). Compared with SAP group, the serum levels of AMS in LC group were significantly decreased(P<0.01). Compared with sham group,the serum levels of IL-6 and TNF-α in SAP group were increased significantly(P <0.01). Compared with SAP group, the serum levels of IL-6 and TNF-α in LC group were significantly decreased(P<0.01). Compared with sham group, the pathological alterations in the pancreas were significantly higher in SAP group(P <0.01), and the pathological score was significantly increased.Compared with SAP group, the pathological alterations and pathological scores of pancreas were significantlydecreased in LC group(P<0.01). Compared with sham group, the serum levels of MPO and the pathological alterations in the lung tissue were significantly higher in SAP group(P<0.01), and the pathological score was significantly increased.Compared with SAP group, the serum levels of MPO,the pathological alterations and pathological scores of lung tissue were significantly decreased in LC group(P<0.01).Compared with sham group,immunohistochemistry scores of intestinal mucosa Akt and MAPK(ERK1/2) were significantly attenuated in SAP group(P<0.01).Compared with SAP group,immunohistochemistry scores of intestinal mucosa Akt and MAPK(ERK1/2) were significantly decreased in LC group(P<0.01).Conclusions:Alveolar macrophages(AM)play an important role in the lung injury of SAP. LC can selectively remove AM, reduce the expression of Akt and MAPK(ERK1/2),reduce the generation of inflammatory cytokines, and protect the lung injury in SAP rats.