银杏叶提取物对人工衰老大鼠肺肾功能的保护作用

背景衰老大鼠静脉注射脂多糖后能导致肺损伤,进而发现随着肺损伤的进展,影响肾功能.银杏叶提取物具有一定的清除自由基、改善血液流变学和保护血管内皮细胞等功能. 目的研究人工衰老大鼠肺损伤后是否发生肾功能不全,以验证老年多器官功能不全的肺启动机制,并观察银杏叶提取物对其是否有保护作用. 设计以实验动物为观察对象的随机对照的实验. 单位中国协和医科大学基础医学研究所病理生理学系. 材料实验于2001-05/2003-01在中国协和医科大学基础医学研究所病理生理学系实验室完成.选用36只Wistar雄性大鼠. 方法给大鼠每天1次经腹腔注入D-半乳糖(50 mg/kg),连续6周,复制衰老动物模型,再随机分为3组对照组(静脉注射生理盐水);脂多糖组(静脉注射脂多糖,5 mg/kg);银杏叶提取物+脂多糖组(注射脂多糖前7 d开始,每天银杏叶提取物灌胃1次,31 mg/kg).各组大鼠在给生理盐水或脂多糖后2 h或6 h取血和肺、肾组织. 主要观察指标用比色法测定血中肌酐、尿素氮含量;血、肺、肾组织中丙二醛、No2-/NO3-含量及谷胱甘肽过氧化物酶及Na+-K+-ATP酶活性的测定. 结果衰老大鼠在注射脂多糖后2,6h时已形成急性肺损伤.注射脂多糖 后2 h血中肌酐及尿素氮含量无明显升高,而6 h时均显著升高,分别为 (94.7±10.3)μmol/L,(11.4±1.9)mmol/L.在注射脂多糖后2h,血和肺组织 中丙二醛(22.5+2.6)nmol/L,(25.8±2.9)μmol/gl和No2-/NO3-含量(58.5 ±6.8)mmol/L,(34.6±3.8μmol/g]均显著升高,而谷胱甘肽过氧化物酶 (355.1±45.0)μkat/g]及Na+-K+-ATP酶(886.3±97.1)nkat/g]下降.上述指标 的变化持续至观察的6 h.而肾组织中上述指标仅在注射脂多糖后6 h才 有显著性变化.银杏叶提取物可显著缓解上述指标的变化. 结论脂多糖所致衰老大鼠的肺损伤可进一步诱导肾功能受损.银杏叶 提取物对脂多糖诱发的衰老大鼠的急性肺损伤和由此诱导的肾功能受 损有明显的保护作用.

Protective effect of ginkgo biloba extract on lung and kidney function in artificial aging rats

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 (355.1 45.0)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.