ABSTRACT
Objective: To investigate the effects of grasp seed procyanidins(GSP,原青花素) on lipopolysaccharide(LPS)induced acute lung injury(ALI) in rats with renal function damage and the related possible molecular mechanisms.Methods: The homogenates of lung and kidney were prepared and venous blood were collected at 6 hours after injection of LPS and medicine.The changes of contents of creatinine(Cr),blood urea nitrogen(BUN),lactic acid(Lac) and nitric oxide(NO) in the blood were measured.The enzyme linked immunosorbent assay(ELISA) was used to measure the levels of tumor necrosis factor?(TNF-?),interleukin-1?(IL-1?),monocyte chemoattractant protein-1(MCP-1) and IL-6 in the serum,lung and renal cortex tissue homogenate in various groups.The histopathological changes of lung tissues were observed.The pulmonary vascular permeability and the lung wet/dry(W/D) weight ratio were determined;the malonaldehyde(MDA) content,Na+K+-ATPase,superoxide dismutase(SOD),myeloperoxidase(MPO) and glutathion peroxidase(GSH-Px) activities in lung and renal tissues were also determined.Changes of mitogen activated protein kinase(MAPKs) were detected by Western blotting,and the combination activity of nuclear factor-?B(NF-?B) to DNA was detected by electrophoretic mobility shift assay (EMSA) in lung tissues.Results: ①Compared with the normal rats in control group,the lungs of the rats in LPS treatment group and GSP group had significant hyperemia and spotted hemorrhage.The inflammatory granulocyte infiltration,diffuse alveolar septum thickening and spotted hemorrhage were observed in the pathological examinations,while in LPS plus GSP group the above mentioned pathological changes were milder.②Compared with control group,the lung W/D and pulmonary vascular permeability were much higher in the LPS treatment groups(P
ABSTRACT
AIM:To investigate the effects of grasp seed procyanidins(GSP) on homocysteine-induced proliferation and migration in vascular smooth muscle cells(VSMC) and related molecular mechanisms.METHODS: Cell count and -TdR assay were used for detecting cell proliferation and DNA synthesis,ELISA assay was used for detecting inflammatory response,DCFH-DA assay for examining the levels of reactive oxygen species(ROS),Western blotting for detecting protein expression.RESULTS: Homocysteine(0.1-1 mmol/L) increased VSMC proliferation and migration,and the levels of ROS were in a dose-dependent manner.The results of Western blotting showed that homocysteine significantly increased the expression of MCP-1,IL-6 and TNF-?.However,Compared with control group,in GSP(5-20 g/L) group,the increased VSMC proliferation,migration and the production of ROS and the expression of MCP-1,IL-6 and TNF-? mediated by homocysteine were markedly suppressed.EMSA showed that in GSP treatment group,the NF-?B activation was also almost completely inhibited.CONCLUSION: GSP inhibits homocysteine-induced VSMC proliferation,migration and inflammatory response through interfering with ROS dependent on NF-?B signal pathway.