盐酸右美托咪啶对缺血再灌注肾损伤小鼠的肾小管保护作用

Protective effect of Dexmedetomidin on kidney injury induced by renal ischemia-reperfusion and its mechanism

摘要:

目的  缺血再灌注肾损伤（IR）是围手术期常见的疾病，本研究通过构建缺血再灌注肾损伤模型，观察右美托咪啶（Dex）注射对受损肾小管的保护作用及机制。方法  将60只小鼠随机分为对照组、IR模型组和IR+Dex组（简称Dex组），制备IR模型后24 h分别处死3组小鼠取肾组织。用全自动生化分析仪测定血肌酐（Scr）及尿素氮（BUN）。采用HE染色观察各组小鼠肾组织的形态，评定肾小管损伤程度；免疫组织化学染色测定低氧诱导因子-1α（HIF-1α）、单核细胞趋化蛋白-1（MCP-1）的表达。结果  对照组的肾小管结构与形态均正常。IR模型组肾小管损害明显、HIF-1α及MCP-1表达均增高。而Dex组肾小管损害程度较轻，HIF-1α及MCP-1表达均较IR模型组减低，肾小管上皮细胞低氧程度及炎症反应均较IR模型组明显减轻。Dex组小鼠的血肌酐及尿素氮水平较IR模型组明显降低。结论  Dex可以通过抑制炎症反应、减轻肾小管上皮细胞低氧程度从而减轻IR小鼠肾小管的损害，保护肾脏功能。

Abstract:

Objective To establish a mouse model of ischemia-reperfusion injury (IRI) and to investigate the protective effects of Dexmedetomidine (Dex) injection on renal tubules, so as to provide new available methods for acute kidney injury (AKI). Methods Sixty female mice were randomly divided into three groups: control group, renal IRI group and Dex group, with 20 mice in each group. The mice were sacrificed at the 24th hour after surgery, then the bilateral kidneys and blood samples were collected. The blood urea nitrogen (BUN) and serum creatinine (Scr) were measured by automatic biochemistry analyzer. HE staining was used to observe the pathology of the kidneys. Immunohistochemistry and Western blot were used to detect the expression of hypoxia inducible factor-1α (HIF-1α) and monocyte chemoattractant protein-1(MCP-1). Results There was no significant changes of renal tubules in the control group. In the renal IRI group, renal tubular epithelial cells were obviously damaged, and their expressions of HIF-1α and MCP-1 noticeably increased. However, renal tubular injury in the Dex group was lighter than that of the IR group; the expressions of HIF-1α and MCP-1, the hypoxia degree and inflammatory reaction of renal tubules as well as the levels of BUN and Scr of the Dex group were lower than those of the IR group. Conclusions  It may be naturally speculated that Dex can protect renal function through reducing inflammatory reaction and hypoxia degree of damaged renal tubular epithelial cells following renal IR.