阿托伐他汀对慢性肾病大鼠血清及肾组织microRNA-92a表达的影响  

Effect of atorvastatin in reducing expression of microRNA-92a in serum and kidney tissue of rats with chronic kidney disease

作　　者：赵婷婷 郭娟英[2] 尚粉青[1] 王慧[1] 程曼丽[1] 郭瑄[1] ZHAO Ting-ting;GUO Juan-ying;SHANG Fen-qing(Xi'an First Hospital,Xi'an,Shanxi 710002,China)

机构地区：[1]西安市第一医院(西北大学附属第一医院)心内科,陕西西安710002 [2]西安建筑科技大学医院

出　　处：《实用医药杂志》2019年第12期1108-1111,1117,共5页Practical Journal of Medicine & Pharmacy

基　　金：国家自然科学基金青年基金项目（8180037）;陕西省卫生健康科研项目（2018D005)

摘　　要：目的明确阿托伐他汀对慢性肾病的保护作用部分是通过其对microRNA-92a/KLF2通路的影响实现的。方法24只健康SD大鼠随机分为正常对照组、肾病组和治疗组。肾病组与治疗组均行5/6肾脏切除制备动物模型,治疗组给予阿托伐他汀6 mg/kg·d进行干预治疗,肾病组和正常对照组每天给予等量的生理盐水灌胃,大鼠自由进食、饮水。末次术后8周处死大鼠。测定血生化,使用ELISA方法测血清中hs-CRP及IL-1β含量;采用RT-PCR方法测定血清及肾组织中miR-92a的含量;用RT-PCR和Western Blot方法测定肾组织中KLF2及其mRNA的表达。结果5/6肾脏切除术后8周,血尿素氮(BUN)、肌酐(SCr)明显增高(P<0.01),肾功能异常,miR-92a表达增加,KLF2表达减少,炎症指标hs-CRP及IL-1β明显增加。阿托伐他汀治疗后血清及肾组织miR-92a均显著下降,KLF2表达较肾病组增加,hs-CRP及IL-1β表达较肾病组明显下降。结论阿托伐他汀除纠正脂代谢紊乱外,还可以有效降低血清及肾组织miR-92a表达,使KLF2表达增加,抑制CKD炎症反应,延缓肾功能不全进展。Objective To clarify the protective effect of atorvastatin on chronic kidney disease through its effect on the microRNA-92a/KLF2 pathway.Methods Tuenty-four healthy SD rats were randomly divided into normal control group,model group and treatment group.In the model group and the treatment group,5/6 kidney resection was performed on the rats to prepare the animal model.The treatment group reserved atorvastatin 6mg/kg.All the rats were killed after 8 weeks from the last operation.Blood biochemistry was determined and the content of hs-CRP and IL-1βlevel in serum was detected by ELISA.The level of mir-92a in serum and kidney tissues was determined by RT-PCR.The expression of KLF2 and its mRNA in renal tissues was determined by RT-PCR and Western Blot.Results At 8 weeks after the last operation,blood urea nitrogen(BUN),creatinine(SCr)were increased significantly,the expression of mir-92a did so,but the expression of KLF2 was decreased.Also,the inflammatory markers hs-CRP and IL-1βwere significantly increased.The serum and renal tissue mir-92a significantly decreased after atorvastatin treatment,the expression of KLF2 was higher than that of the model group,and the expression of hs-CRP and IL-1βwas significantly lower than that of the model group.Conclusion In addition to correcting lipid metabolic disorders,atorvastatin can also effectively reduce expression of mir-92a in serum and renal tissues,increase expression of KLF2,inhibit inflammatory response of CKD,and delay the progression of renal insufficiency.

关 键 词：阿托伐他汀 microRNA-92a KLF2 慢性肾病 炎症反应 

分 类 号：R692:R-333[医药卫生—泌尿科学]