脂肪干细胞联合右旋美托咪定对大鼠急性肾缺血再灌注损伤的保护作用

Protective effect of adipose-derived mesenchymal stem cells combined with dexmedetomidine for acute ischemia-reperfusion injury in rats

目的评估脂肪干细胞联合右旋美托咪定对大鼠急性肾缺血再灌注损伤的保护作用。方法雄性SD大鼠40只,随机分为五组:Sham组、肾缺血再灌注损伤组(IR组)、右旋美托咪定处理组(IR+DEX组)、脂肪干细胞处理组(IR+ADSCs组)和联合处理组(IR+DEX+ADSCs组)。分离培养脂肪干细胞,建立大鼠肾缺血再灌注模型,按分组给予尾静脉注射ADSCs(1×10^(6))或及腹腔注射右旋美托咪定(25μg/kg)。分别于0、24、96 h采血检测肾功能指标:血肌酐(Scr)、尿素氮(BUN)水平,同时检测尿蛋白(UP)及尿肌酐(UC)的含量,并计算其比值(UP/UC);于96 h麻醉下处死大鼠,取肾组织行HE染色及组织病理损伤评分。结果与IR组比较,IR+DEX组或IR+ADSCs组Scr、BUN及UP/UC降低(P <0.05),同时肾组织病理损伤评分显著改善(P <0.05);与IR+DEX组或IR+ADSCs组比较,IR+DEX+ADSCs组上述指标进一步降低(P <0.05)。结论在大鼠急性肾缺血再灌注损伤模型中,与单独使用ADSCs或右旋美托咪定比较,两者联合使用具有更好的肾脏保护作用。

Objective To assess the protective effect of adipose-derived mesenchymal stem cells(ADSCs) combined with dexmedetomidine on acute ischemia-reperfusion injury(IRI)in rats. Methods Fortyadult healthy SD male rats were randomly divided into sham-operated group,ischemia reperfusion injury group(IR group),dexmedetomidine-treated group(IR+DEX group),ADSCs-treated group(IR+ADSCs group)and dexmedetomidine combined with ADSCs-treated group(IR+DEX+ADSCs group). Isolated ADSCs were cultured in suitable incubation conditions and the IRI model in rats was established. The rats received cell suspension of ADSCs(1 × 10^(6))through tail vein or/and received intraperitoneal injection of dexmedetomidine 25 μ g/kg in different groups.The plasma samples of each group were harvested for determining the level of serum creatinine(Scr)and blood urea nitrogen(BUN)at 0,24 h and 96 h. Urine samples of rats of each group were collected at the same time for detecting urine protein(UP)and urine creatinine(UC),and calculating the ratio of urine protein/creatinine(UP/UC). The rats were euthanized after anesthetization and kidney specimens were collected for HE staining at96 h after the experimental treatment,and the histopathology injury of kidney were scored. Results When compared with that in IR group,the level of Scr,BUN and UP/UC decreased significantly in IR+DEX group and IR+ADSCs group(P < 0.05),meanwhile the injury of kidney was also significantly reduced in two groups. When compared with that in IR+DEX group and IR+ADSCs group,the above indicators in IR+DEX+ADSCs group further decreased and was statistically significant(P < 0.05). Conclusion In rat model of acute renal ischemia-reperfusion injury,the combination of ADSCs with dexmedetomidine has better renal protection effect when compared with single ADSCs or dexmedetomidine treatment.