肾脂肪囊内注射黄芪和多巴胺对大鼠内毒素休克所致急性肾衰竭的防治作用

Effects of Astragalus and Dopamine Injected Into Renal Adipose Capsule on Acute Renal Failure in Rat Endotoxic Shock Model

目的:探讨肾脂肪囊内联合应用黄芪和多巴胺对大鼠内毒素休克所致急性肾衰竭的防治作用及其机制。方法:SD大鼠随机分为对照组、内毒素组、静脉应用与肾脂肪囊内应用黄芪和多巴胺组,分别测定平均动脉压(MAp)、肾血浆流量(RPF)、肾小球滤过率(GFR)、尿量(UO)、滤过钠排泄分数(FENa)以及肾组织一氧化氮(NO)和内皮素(ET)浓度,光镜及电镜观察病理改变。结果:内毒素组MAp和RPF、GFR、UO显著降低,FENa初4h极度减少,随后增高,至12h后接近或大于2%,肾组织NO和ET浓度明显升高;黄芪和多巴胺联合应用可稳定MAp,提高RPF和GFR,增加UO,改善FENa,降低肾组织NO和ET水平,减轻组织病理损害,尤以肾脂肪囊内给药组肾脏保护效果显著,实验后期作用更为明显。结论:黄芪和多巴胺联合应用可纠正大鼠内毒素休克低血压状态,改善肾脏功能,减轻病理损害,可能与作用于NO和ET系统有关。

Objective:To investigate the effects of astragalus and dopamine injected into renal adipose capsule on acute renal failure in endotoxic rats.Methods:Eighty male SD rats were randomly divided into 4 groups:control,lipopolysaccharide (LPS), intravenous injection with astragalus and dopamine and renal adipose capsule injection with astragalus and dopamine. The mean artery pressure (MAp),renal plasma flow (RPF),glomerular filtration rate (GFR), urine output (UO) and fractional excretion of filtered sodium (FENa) were evaluated at 4 h, 8 h,12 h and 16 h respectively.The levels of nitric oxide (NO) and endothelin (ET) in renal tissue were also measured.Renal histopathologic changes were determined by light and electronic microscopy.Results:MAp,RPF,GFR and UO significantly decreased after intraperitoneal injection of LPS with FENa extremely diminished at 4h and exceeded 2% at 12h and later.The levels of NO and ET in the kidney significantly increased. Combined administration of astragalus and dopamine resulted in a dramatic reversal of the MAp, RPF and GFR and increased UO and improved FENa. The levels of NO and ET in the renal tissue were also reduced, and the renal histopathologic changes were attenuated.Renal adipose capsule injection of astragalus and dopamine induced much better effects than intravenous injection, especially in the late period.Conclusion:In rat endotoxic shock model, combined administration of astragalus and dopamine can prevent hypotension, improve renal function and histopathlogic damage,which may be related to the NO and/or ET systems.Compared to the intravenous injection,renal adipose capsule injection of astragalus and dopamine can result in greater improvement in renal function,which may lead to a feasible and effective strategy in clinical practice.