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Objective To explore the role of MAPK and NF-?B in the increase of Toll-like receptor 4(TLR4) expression induced by lipopolysaccharide(LPS) in pulmonary micro-vascular endothelial cells(PMVECs) of mouse.Methods PMVECs were isolated,cultured and exposed to the different concentration LPS at(2 h),and(100 ?g/L) LPS in different time.The concentration of TNF-? in culture supernatant was detected using ELISA.(Using) PD98059 inhibitor for ERK,SB203580 inhibitor for P38 MAPK and PDTC inhibitor for NF-?B pretreated(PMVECs).RT-PCR was used to detect the levels of TLR4 and TNF-? mRNA.Western-blot was used to detect the protein expression of nuclear factor-kappa B(NF-?B) P65 subunit and ERK / P38 MAPK in nuclear extract after LPS exposure for 6 h respectively.Results With the treatment of 50～(500 ng /mL) LPS for(2 h) or(100 ?g /L)(LPS exposure) in different time,the concentration of TNF-?in culture supernatant of PMVECs was increased by a time and dosage dependent style(P
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BACKGROUND:Lung injury can be induced after injection of lipopolysaccharide(LPS) into the vein of aging rats,and with the development of lung injury,the kidney function can be influenced.Ginkgo biloba extract(GBE) has some effects such as clearing the free radicals,improving hemorrheology,protecting the vascular endothelial cells and so on. OBJECTIVE:To investigate whether renal function damage is induced by acute lung injury(ALI) in aging rats so as to support the hypothesis that lung is the start-up organ in multiple organ dysfunction syndrome in the elderly and the protective effect of GBE on it. DESIGN:Randomized controlled experimental trial based on the experimental animals. SETTING:Laboratory of Department of Pathophysiology,Institute of Basic Medical Science,Peking Union Medical College. MATERIALS:The study has been completed from May 2001 to January 2003 in the Laboratory of Department of Pathophysiology,Institute of Basic Medical Science,Peking Union Medical College.Thirty-six Wistar male rats were involved. INTERVENTIONS:For reproducing the mimic aging rats models,the rats were injected intraperitoneally,D-gal 50 mg/kg,once a day,for 6weeks totally,and randomly divided into 3 groups, namely: ①control group(saline ,intravenous injection);② LPS group( LPS,5 mg/kg intravenous injection) ③ GBE+LPS group (GBE was used 7 days prior to LPS,31 mg/kg ,once a day).Samples(blood,lung and kidney tissue) were collected at 2 or 6 hours after LPS or saline administration. MAIN OUTCOME MEASURES:Contents of creatinine(Cr),blood urea nitrogen (BUN),lactic acid (LA),NO (its metabolite is NO2-/NO3-) and methane dicarboxylic aldehyde(MDA);and activities of glutathione peroxi-dase(GSH-Px) and Na+-K+-ATPase were measured. RESULTS:Compared with control group,there was obviously ALI at 2or 6 hours after LPS administration.Cr [(94.7±10.3) μmol/L]and BUN [(l1.4 1.9)mmol/L]contents in blood were increased significantly until 6 hours after LPS administration.In LPS group,MDA[(22.5 2.6) nmol/L]and NO2-/NO3-[(25.8 2.9) μmol/g] contents in blood and in lung tissue were all increased significantly at 2 hours.But GSH-PX [(355.145.0)μkat/g],Na+-K+-ATPase [(886.3 97.2) nkat/g] activities in lung tissue were decreased significantly at 2 hours after LPS administration.The above changes lasted for 6 hours.However,significant change did not occur until 6 hours after LPS administration in renal tissue.All the above changes were markedly attenuated by pretreatment of GBE. CONCLUSION:ALI was caused by LPS intravenous injection in aging rats.Renal function damage could be induced by ALI in aging rats.GBE showed a protective effect on ALI and renal function damage in this animal model.
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Objective To investigate whether gingko biloba extract (GBE) have protective effect on acute lung injury(ALI)induced by Lipopolysaccharide ( LPS) in aging rats and renal function damage induced by ALI. Methods Male aging Wistar rats(36) were used in the study. LPS group (LPS, iv route, 5mg/kg body weight) and GBE+LPS group (GBE was given starting from 7 days before experiment, once a day oral administration). The blood, lung and kidney samples were collected at 2 or 6 hours after LPS or saline administration. Results Compared with the aging control, ALI was obviously observed in LPS group, blood creatinine and urea nitrogen were increased significantly from (68.7? 6.9) mol/L and (5.9?0.6) mmol/L to (94.7?10.3) mol/L and (11.4?1.9) mmol/L, respectively (P
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AIM:To investigate whether renal function damage could be induced by acute lung injury(ALI)in aging rats. METHODS: 40 Wistar male rats were used for reproducing aging animal model. Aging rats were randomly divided into aging control; ALI group (Lipopolysaccharide, LPS, 5 mg/kg body weight, iv) and LPS group (same dosage LPS, intraventricle of left heart injection). The samples (blood, lung and kidney ) were collected at 2 or 6 hours after LPS or normal saline administration. RESULTS:Compared with aging control, in ALI group, creatinine (Cr) and urea nitrogen (BUN) contents in blood were increased significantly (all P