Protective Effect Of Angiopoietin-1 On Acute Lung Injury Induced By Oleic Acid At Early Stage In Mice

Objective To investigate the effects of angiopoietin-1 and angiopoietin-2 on acute lung injury(ALI)induced by oleic acid at early stage in mice and to observe the changes of vascular endothelial growth factor (VEGF).Methods 144 BALB/C female mice were randomly divided into 6 groups(n = 24 each). The control group (Group A)was given normal saline(0.9ml/kg); ALI group(Group B) in which ALI was induced by oleic acid(0.9ml/kg) intravenously; In control+angiopoietin-1 group(Group C), the mice received intraperitoneal injection of angiopoietin-1(312.5μg /kg in 1ml saline) was given after normal saline for 4h. In ALI +angiopoietin-1 group ( Group D ) the mice received intraperitoneal injection of angiopoietin-1(312.5μg /kg in 1ml saline) after oleic acid was given 4h later. In control+angiopoietin-2 group ( Group E ) , the mice received intraperitoneal injection of angiopoietin-2(312.5μg /kg in 1ml saline) was given after normal saline for 4h. In ALI +angiopoietin-2 group(Group F) the mice received intraperitoneal injection of angiopoietin-2(312.5μg /kg in 1ml saline) after oleic acid was given 4h later. Then each group was randomly divided into 2 subgroups(n = 12 each).GroupⅠ: protein level, cell count and differentials in brochoalveolar lavage fluid(BALF) were detected. The levels of IL-6 and VEGF in both serum and BALF were measured by enzyme-linked- immunosorbent assay (ELISA). GroupⅡ: wet/dry weight(W/D) of right lung was recorded. Pathological changes of left lung and VEGF expressions in lung tissue were examined. The expression of VEGF was immunohistochemically detected in lung tissues as integrated optic density (IOD) measured with Image Pro Plus 5.1 software. Results: W/D, protein level, tota1 cel1 number and classification of polymorphonuclear leukocytes(PMN) in BALF,IL-6 level in both serum and BALF,VEGF level in serum were significantly lower in Group D [(4.10±0.14),(175.83±13.42)μg/ml,(34.42±4.14)×10~4/L,(19.85±3.93)×10~3/L,(652.07±16.91)pg/ml,(1317.51±61.62)pg/ml,(47.94±4.67)pg/ml] as compared to the ALI group([5.33±0.51),(227.25±11.93)μg/ml,(42.17±5.24)×10~4/L,(26.22±2.22)×10~3/L,(743.60±12.98)pg/ml,(1509.46±116.90)pg/ml,(74.32±5.01 )pg/ml] (P < 0.05), but VEGF level in BALF in Group D [(178.54±14.77)pg/ml ]were significantly higher than those in Group B [(140.09±20.24) pg/ml] (P<0.05). The expressions of VEGF described by IOD(549±73) in Group D were significantly higher than those in Group B (342±85) in lung tissue, but significantly lower than that in Group A (761±111) (P <0.05). There was no difference among Group C,Group E and Group A(P >0.05), There was also no difference between Group F and Group B(P >0.05)Conclusion: It is suggested that angiopoietin-1 may help to relieve the severity of acute lung injury induced by oleic acid in mice at early stage and could up-regulate VEGF expression in BALF and lung tissue but down-regulate VEGF expression in serum . Angiopoietin-2 maybe a factor which isn't relate to ALI induced by oleic acid at early stage in mice. VEGF and angiopoietin-1 maybe two necessary factors in the mechanism of ALI induced by oleic acid at early stage in mice.