阿托伐他汀对糖尿病大鼠肾脏NF—κB表达影响的实验研究  

Experimental study of influence of atrovastatin on the expression of NF-κB in renal tissues of diabetic rats

作　　者：于晓静[1] 王晓梅[1] 侯云华[1] 隋淼[1] 朱瑞萍[2] 

机构地区：[1]大连大学附属中山医院内分泌科,辽宁省大连116001 [2]大连大学附属中山医院病理科,辽宁省大连116001

出　　处：《中国医师杂志》2012年第7期885-888,共4页Journal of Chinese Physician

基　　金：辽宁省大连市卫生局资助课题（【2009】67）

摘　　要：目的探讨他汀类药物对糖尿病大鼠肾脏NF—κB表达的影响及其可能机制。方法雄性sD大鼠60只，随机抽取40只腹腔注射链脲佐菌素65mg／kg建立糖尿病模型，余20只为正常对照组（NC）。成模大鼠随机分成两组，糖尿病非药物干预组（DM）及阿托伐他汀干预组（DA）。DA组予阿托伐他汀2mg／（kg·d）灌胃，NC组及DM组给予等量饮用水。大鼠12周后处死，取一肾组织抽提RNA，另一肾组织固定后做免疫组化。应用Rt—PCR扩增NF—κB基因，比较3组大鼠的NF-κBmRNA表达。免疫组织化学方法检测NF—KB蛋白表达情况。结果RT—PCR结果示DM组大鼠肾组织中NF-KBmRNA表达较NC组大鼠明显增高（P〈0．05），DA组大鼠NF—κB的表达比DM组明显减少（P〈0．05）。免疫组织化学结果显示NF—κB在肾小管及肾小球均有表达，DM组大鼠肾脏NF—κB阳性的细胞比NC组明显增多（P〈0．05），且着色较深。DA组的大鼠中，NF-κB阳性的细胞比DM组明显减少（P〈0．05），且着色较浅。结论阿托伐他汀能降低糖尿病大鼠肾组织中NF-KBmRNA及NF-κB蛋白质的表达，减缓肾组织病变进展。Objective To explore the effects and mechanism of atrovastatin on the expression of the NF-κB in renal tissues of diabetic rats. Methods A total of 60 male SD rats was randomly taken out 40 rats to make diabetic model by injection of 65mg streptozotocin （STZ） into enterocoelia, the rest of 20 rats were normal control group. After the model made, atrovastatin （2 mg/kg/d） was given to the treated group, and the normal control group and diabetic rats without treatment group were given equivalent water. After 12 weeks, the rats were killed. Total RNA of the renal tissues was isolated from one kidney for each rat, and the renal tissues from the another kidney was prepared for immunohistochemistry （IHC） analysis. The NF- κB mRNA expressions among three groups were determined by RT-PCR. The distribution of NF-κB in the renal tissues was observed, and compared its difference among three groups. Results PCR showed that NF-κB mRNA was increased in the renal tissues of diabetic rats compared to control rats （ P 〈 0. 05 ）. Drug-treated rats showed significantly decreased levels of NF-κB mRNA in the renal tissues compared to the untreated diabetic group（ P 〈0. 05）. The results were also observed in protein lelel of NF-κB expression. IHC showed that there existed positive cells in the glomerular and renal tubulointerstitum. Conclusions Atrovastatin can down-regulate the expression of NF-κB and suppress the increased level of NF-κB protein in the renal tissue of diabetic rats, and slow the progress of retinopathy.

关 键 词：降血脂药/药理学 阿托伐他汀 糖尿病肾病/代谢 NF—κB/代谢 大鼠 

分 类 号：R692[医药卫生—泌尿科学] R587[医药卫生—外科学]