瑞舒伐他汀对大鼠造影剂急性肾损伤的保护作用及机制

The Prevention Mechanism of Rosuvastatin on Contrast-induced Acute Kidney Injury in Rats

通过建立大鼠非离子低渗型造影剂急性肾损伤模型,探讨瑞舒伐他汀对大鼠非离子低渗型造影剂急性肾损伤的保护作用及机制。将36只健康成年SD大鼠随机分组:正常对照组(NS组);造影剂对照组(CM组);瑞舒伐他汀干预组(RV组)。RV组于注射造影剂前12 h按10 mg/kg瑞舒伐他汀混悬液灌胃,NS组、CM组灌胃等量生理盐水。CM组、RV组以10m L/kg剂量行大鼠尾静脉注射造影剂(优维显370,370 mg I/m L),NS组注射等量的生理盐水,分别在造影24 h和72 h后取材。使用苏木精-伊红(HE)染色法,观察肾小管的病理形态学变化。测定血清胱抑素C(Cys-C)、血清肌酐(Scr)、尿α1-微球蛋白(α1-MG)、尿微量白蛋白(m ALB)、尿N-乙酰-B-D-葡萄糖酸苷酶(NAG)水平,以评估大鼠肾脏功能变化。测定血清超敏C反应蛋白(Hs-CRP)以及肾组织中超氧化物歧化酶(SOD)活性,以评估炎症和氧化应激反应。结果表明:1与CM组大鼠相比给予瑞舒伐他汀治疗能明显减轻大鼠肾脏损伤程度;2 CM组和RV组大鼠血Scr、血Cys-C、尿NAG、尿α1-MG、尿m ALB均较NS组显著升高,给予瑞舒伐他汀治疗组大鼠与CM组大鼠相比,上述各项指标均显著下降(p<0.05);组内比较,CM组大鼠上述各项指标72 h较24 h上升显著(p<0.05),其余各组无明显差异(p>0.05);3 CM组和RV组大鼠血清Hs-CRP水平均较NS组明显升高,RV组较CM组血清Hs-CRP降低显著(p<0.01);组内血清Hs-CRP比较,CM组大鼠随时间升高明显(CM 24 h vs CM 72 h,p<0.05),给予瑞舒伐他汀治疗组大鼠则明显下降(RV 24 h vs RV 72 h,p<0.05);4CM组和RV组大鼠肾组织SOD活性均较NS组明显降低,RV组与CM组相比SOD活性显著升高(p<0.01);组内比较,CM组大鼠肾组织SOD活性随时间降低明显(CM 24 h vs CM 72 h,p<0.05),而RV组大鼠肾组织SOD活性随时间显著升高(RV 24 h vs RV 72 h,p<0.05)。说明短期瑞舒伐他汀干预通过降低血浆细胞炎症因子水平、降低造影剂肾病大鼠肾脏氧化应激水平,减轻造影剂肾病大鼠肾脏的损伤程度,对造影剂肾病大鼠具有一定程度的保护作用。

To explore the mechanism of rosuvastatin protection on low-osmolar and nonionic contrast-induced acute kidney injury in rats,Randomly classified 36 healthy SD rats into 3 groups： normal control group（ NS group）,contrast media control group（ CM group） and rosuvastatin control group（ RV group）. Before injected contrast media,RV group received rosuvastatin 10 mg / kg through oral gavage 12 hours in advance,0. 9% Na Cl solution（ 10 mL/kg） insteaded of contrast media in the other groups. Through caudal veins low-osmolar contrast media was injected of all rats,and 0. 9% Na Cl solution（ 10 mL / kg） insteaded of contrast media in the NS group. There were two small groups were divided from each of groups,and the sample were collected at 24 h and 72 h respectively after contrast media was injected. The pathological changes of renal tubule was assessed by histologic examination（ HE staining）. The levels of serum Cys-C,Scr,urine α1-MG,mALB and NAG were determined to assess the changes of rat kidney function. Serum Hs-CRP and SOD activity in kidney tissues were determined to evaluate the inflammatory and oxidative stress. It is resulted that ① Rosuvastatin showed excellent protective effects alleviate contrast media induced tissue damages compared with the group of contrast renal injury; ②The levels of serum Cys-C,Scr,urine α1-MG,mALB and NAG in the model group and the treatment group were higher than the normal control group,and compared with contrast media control group,the above indicators all decreased in rosuvastatin control group（ p〈0. 05）. Comparison in groups,all of the indicators above were increased with time in contrast media control group（ RV 24 h vs RV 72 h,p〈0. 05）,while the other groups had no significant difference（ p〉0. 05）; ③ Compared with the normal group,the Hs-CRP in serum was increased obviously in model group and treatment group,and it was significant decreased in rosuvastatin control group compared with contrast media control group（ p〈0. 01）. Comparison in groups,the indicator above were increased with time in contrast media control group（ RV 24 h vs RV 72 h,p〈0. 05）,while there was on the contrary in rosuvastatin control group（ RV 24 h vs RV 72 h,p〈0. 05）; 4 The activity of SOD was decreased in contrast media control group and rosuvastatin control group than normal control group. To compare contrast media control group,the activity of SOD was significant increased in rosuvastatin control group（ p〈0. 01）. The activity of SOD was lower at 72 hour than 24 hour in contrast media control group（ p〈0. 05）,while there was on the contrary in rosuvastatin control group（ RV 24 h vs RV 72 h,p〈0. 05）. It is conclused that rosuvastatin alleviated the injuries of kidney eventually through suppressing the levels of plasma cytokines and decreasing oxidative stress. Studies show that rosuvastatin could pay a protective role in low-osmolar and nonionic contrast-induced acute kidney injury in rats.