右美托咪定对脓毒血症大鼠肾功能及紧密连接蛋白表达的影响

摘要

目的：探讨右美托咪定对脓毒血症大鼠肾功能及紧密连接蛋白表达的影响。方法 SD大鼠30只，随机分为右美托咪定处理组（ Dex组）、脓毒血症模型组（ M组）、生理盐水对照组（ C组），每组10只。 Dex组大鼠静脉注射脂多糖（ LPS）5 mg／kg，之后泵注Dex 7μg／kg，15 min后调整剂量为5μg／kg· h，持续泵注30 min；模型组按同样方法给予LPS后泵注生理盐水；C组始终采用上述方法给予生理盐水。24 h后取血液分离血浆，多功能生化仪检测肌酐（ Scr）和尿素氮（ BUN）含量；ELISA检测IL-1β和TNF-α含量；Western blot检测肾组织中紧密连接蛋白ZO-1和occludin的表达变化。结果与C组相比，模型组损伤较重，可见大量炎性细胞浸润，有肾小球肾炎表现，而Dex组未见明显的炎症细胞，细胞异常较少，与模型组相比，损伤减轻。肾功能及炎性因子检测结果显示，与C组比较，各组血浆中Scr、BUN、IL-1β和TNF-α含量均显著升高（P＜0.05），ZO-1和occludin蛋白表达水平均下降（P＜0.05）；与模型组比较，Dex组各项指标均明显降低（P＜0.05），ZO-1和occludin蛋白表达水平均升高（P ＜0.05）。结论右美托咪定可改善脓毒血症所致的急性肾损伤的肾功能，抑制炎症反应，提升紧密连接蛋白，对肾脏有一定的保护作用。%Objective To investigate the effect of dexmedetomidine on the renal function and the expression of tight junction protein ZO-1 and occluding in the kidney of rats with septicopyemia induced by lipopolysaccharide.Methods Thirty adult male SD rats were randomly divided into 3 groups ( n=10 each):control group( group C) , LPS group ( group M) , and dexmedetomidine group ( group Dex ) .In the groups Dex and LPS, the rats were infused with saline and lipopolysaccharide (5 mg/kg, i.v.) respectively.In the Dex group, after intravenous injection of lipopolysaccharide (5 mg/kg) , the rats were firstly infused the loaded dose of dexmedetomidine (7μg/kg) for 15 minutes, and then changed to 5 μg/kg· min for 30 minutes.Blood samples were collected at 24 h later for measuring TNF-α, IL-1β, Scr and BUN.The kidney tissues were examined by histopathology.The expression of ZO-1 and occludin was detected by Western blot. Results Compared with the group C, the kidney tissue of group M was extensively damaged with tubular dilatation and inflammation, while reduced in the group Dex.Compared with the group C, the expressions of Scr, BUN, IL-1βand TNF-αwere all enhanced in the groups M and Dex ( P <0.05 ) , while the inflammatory factors in the group Dex were significantly lower than those of the group M ( P <0.05 ) .The Results The Western blot analysis showed that the expressions of protein ZO-1 and occludin in the group Dex were significantly higher than those of the group M (P<0.05). Conclusions Dexmedetomidine can improve the renal function of rats with septicopyemia, inhibit the acute renal injury and inflammation, increase the expression of protein ZO-1, and exert certain protective effect on the kidneys.