The Role And Mechanism Of Insulin On Acute Lung Injury

Objective:The roles and mechanism of insulin (ISL) in acute lung injury (ALI) by lipopolysaccharide (LPS) induced.Methods:72male SD rats were randomly divided into nine groups:Normal control group, model groups(2h,6h,12h,24h group after the LPS injected), the treatment groups (2h,6h,12h,24h group after the LPS injected). Every group will be injected LPS by the intravenous,and listed as experiment time points "0", model groups intravenous LPS4mg/kg, the treatment groups will be injected insulin (4U/kg) by subcutaneous before2h of the LPS injection. Normal control group will be injected saline with the corresponding time pionts. The blood samples are reserved for blood sugar levels, the serum C peptide and the lung homogenate TNF alpha concentration are determined by ELISA method, immunohistochemistry methods were used in the detection of lung tissue MMP-9and TIMP-1expression; At the same time, The left lung wet and dry weight ratio (W/D) and pathological changes of lung tissue were detected.Results:1、Comparing to the normal control group about1hour after tail intravenous LPS4mg/kg, SD rats become restlessness, less active, slow performance in different degrees; The left lung W/D, pulmonary edema, neutrophils infiltrating, diffuse blood capillary dilate, alveolar cavity hemorrhage, part of the alveolar withering trapped or lung real change and emphysema and lung tissue acute inflammatory pathological changes are heighten after two hours, The ALI animal models are successful by the LPS induced.2、The changes of blood sugar and blood c-peptide levels present the same trend, they are increasing at2h, and get to the highest12h, then they are fell, but still significantly higher than normal group, They are hints of existing insulin resistance phenomenon in ALI by LPS induced.3、The lung homogenate TNF alpha level beginning to rising after2h LPS injected,and get to peak at6h, and less gradually after12h when it still higher than normal control group (P<0.05) at24h; The expression of lung tissue MMP-9and TIMP-1are increasing and the tendency is same, they are increasing at2h, get to peak at12h, but they are still higher than normal control group at24h (P<0.05).4、Comparing to the model groups, the lung tissue pathology are lighten, blood sugar and C peptide levels become lower, the lung homogenate TNF alpha and lung tissue MMP-9expression level are decreased significantly, and the lung tissue TIMP-1expression, MMP-9/TIMP-1drop ratio are increased in the treatment groups rats. Conculsion:(1)The rats of acute lung injury induced by lipopolysaccharide have insulin resistance phenomenon.(2) Insulin therapy can reduce the lipopolysaccharide-induced acute lung injury, which may relate to confronting the phenomenon of insulin resistance, and reducing the level of TNF-α and MMP-9expression, increasing expression of TIMP-1, MMP-9/TIMP-1system into balance.