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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(50mg/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,5mg/kg);银杏叶提取物+脂多糖组(注射脂多糖前7d开始,每天银杏叶提取物灌胃1次,31mg/kg)。各组大鼠在给生理盐水或脂多糖后2h或6h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2h血中肌酐及尿素氮含量无明显升高,而6h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犤(22.5±2.6)nmol/L,(25.8±2.9)μmol/g犦和NO2-/NO3-含量犤(58.5±6.8)mmol/L,(34.6±3.8)μmol/g犦均显著升高,而谷胱甘肽过氧化物酶犤(355.1±45.0)μkat/g犦及Na+-K+-ATP酶犤(886.3±97.2)nkat/g犦下降。上述指标的变化持续至观察的6h。而肾组织中上述指标仅在注射脂多糖后6h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。
BACKGROUND: Aging rats can cause lung injury after intravenous injection of lipopolysaccharide, and then find that with the progress of lung injury, renal function is affected. Ginkgo biloba extract has certain functions such as scavenging free radicals, improving hemorheology, and protecting vascular endothelial cells. OBJECTIVE: To investigate whether renal insufficiency occurred in the lungs of artificially-sensed rats in order to verify the lung initiation mechanism of multiple organ dysfunction in the elderly, and to observe whether Ginkgo biloba extract had protective effects. Design: Randomized controlled experiments with experimental animals. Unit: Department of Pathophysiology, Institute of Basic Medical Sciences, Peking Union Medical College. MATERIALS: The experiment was performed at the Laboratory of Pathophysiology, Institute of Basic Medical Sciences, Peking Union Medical College from 2001-05 to 2003-01. 36 Wistar male rats were used. METHODS: Rats were given intraperitoneal injection of D-galactose (50 mg/kg) once a day for 6 consecutive weeks to replicate an aging animal model and randomly divided into 3 groups: control group (intravenous saline injection); lipopolysaccharide group ( Intravenous injection of lipopolysaccharide, 5mg/kg); Ginkgo biloba extract + lipopolysaccharide group (starting 7 days before the injection of lipopolysaccharide, Ginkgo biloba extract once daily gavage, 31mg/kg). Blood and lung and kidney tissues were collected 2 h or 6 h after administration of saline or lipopolysaccharide in each group of rats. MAIN OUTCOME MEASURES: Determination of creatinine and urea nitrogen in blood by colorimetry; content of malondialdehyde, NO2-/NO3- and glutathione peroxidase and Na+-K+-ATPase in blood, lung, and kidney tissues Determination of activity. RESULTS: Acute lung injury developed in aged rats at 2 and 6 h after lipopolysaccharide injection. The serum creatinine and urea nitrogen levels did not increase significantly at 2 h after lipopolysaccharide injection, but increased significantly at 6 h (94.7±10.3) μmol/L and (11.4±1.9) mmol/L, respectively. At 2h after lipopolysaccharide injection, malondialdehyde (22.5 ± 2.6) nmol/L, (25.8 ± 2.9) μmol/g helium and NO2-/NO3- content (58.5 ± 6.8) mmol/L in blood and lung tissues. ,(34.6±3.8)μmol/g 犦 increased significantly, while glutathione peroxidase 犤(355.1±45.0)μkat/g犦 and Na+-K+-ATPase犤(886.3±97.2)nkat/g犦 descent. Changes in the above indicators lasted up to 6 hours of observation. However, the above indexes in kidney tissue only changed significantly 6 h after lipopolysaccharide injection. Ginkgo biloba extract can significantly ease the changes in the above indicators. CONCLUSION: Lung injury in aged rats induced by lipopolysaccharide can further induce impaired renal function. Ginkgo biloba extract has significant protective effects on acute lung injury and impaired renal function induced by lipopolysaccharide in aging rats.