中华肾脏病杂志
中華腎髒病雜誌
중화신장병잡지
2012年
5期
397-402
,共6页
范秋灵%张丛笑%刘晓丹%杨刚%姜奕%董雪竹%冯江敏%马健飞%张玉侠%王力宁
範鞦靈%張叢笑%劉曉丹%楊剛%薑奕%董雪竹%馮江敏%馬健飛%張玉俠%王力寧
범추령%장총소%류효단%양강%강혁%동설죽%풍강민%마건비%장옥협%왕력저
糖尿病肾病%肾小球%微小RNAs%血管紧张素Ⅱ1型受体拮抗剂%KKAy小鼠
糖尿病腎病%腎小毬%微小RNAs%血管緊張素Ⅱ1型受體拮抗劑%KKAy小鼠
당뇨병신병%신소구%미소RNAs%혈관긴장소Ⅱ1형수체길항제%KKAy소서
Diabetic nephropathy%Glomeruli%miRNAs%Angiotensin Ⅱ type 1 receptor blockers%KKAy mice
目的 分析糖尿病肾病(DN)发病过程中肾小球miRNA表达谱的变化,观察血管紧张素受体拮抗剂(ARB)氯沙坦对DN肾小球miRNA表达谱的影响,确认在DN发病过程中发挥关键作用的miRNA.方法 8周龄KKAy小鼠随机分为氧沙坦治疗组(10 mg·kg-1·d-1)和非治疗组,C57BL/6小鼠作为正常对照组.于20周龄检测体质量、随机血糖、尿微量白蛋白、尿肌酐,观察肾脏形态改变.应用磁珠灌注法分离肾小球,提取总RNA,应用Affymetrix GeneChip miRNA芯片,分析KKAv小鼠肾小球microRNA表达谱的变化,以及氯沙坦对microRNA表达谱的影响.结果 KKAy小鼠的体质量和血糖较正常对照C57BL/6组小鼠显著升高(均P＜ 0.05),氯沙坦治疗显著改善2型糖尿病KKAy小鼠的尿白蛋白/肌酐比值[( 539.71±100.23) mg/g比(728.00±177.19) mg/g,P＜0.05]和肾脏病理损害,而对血糖无影响.miRNA芯片分析结果发现,与正常对照C57BL/6小鼠相比,20周龄KKAy小鼠肾小球内10个miRNA的表达上调；12个miRNA的表达下调.与KKAy非治疗组小鼠相比,20周龄氯沙坦治疗组KKAy小鼠肾小球内共有4个miRNA表达下调,其中miR-503和miR-181d在KKAy非治疗组小鼠肾小球内的表达显著上调,氯沙坦治疗可抑制其过表达.结论 miR-503和miR-181d在糖尿病KKAy小鼠肾小球内的表达显著上调,氯沙坦治疗可抑制其在糖尿病状态下的异常表达,可能为糖尿病肾病新的治疗靶点.
目的 分析糖尿病腎病(DN)髮病過程中腎小毬miRNA錶達譜的變化,觀察血管緊張素受體拮抗劑(ARB)氯沙坦對DN腎小毬miRNA錶達譜的影響,確認在DN髮病過程中髮揮關鍵作用的miRNA.方法 8週齡KKAy小鼠隨機分為氧沙坦治療組(10 mg·kg-1·d-1)和非治療組,C57BL/6小鼠作為正常對照組.于20週齡檢測體質量、隨機血糖、尿微量白蛋白、尿肌酐,觀察腎髒形態改變.應用磁珠灌註法分離腎小毬,提取總RNA,應用Affymetrix GeneChip miRNA芯片,分析KKAv小鼠腎小毬microRNA錶達譜的變化,以及氯沙坦對microRNA錶達譜的影響.結果 KKAy小鼠的體質量和血糖較正常對照C57BL/6組小鼠顯著升高(均P＜ 0.05),氯沙坦治療顯著改善2型糖尿病KKAy小鼠的尿白蛋白/肌酐比值[( 539.71±100.23) mg/g比(728.00±177.19) mg/g,P＜0.05]和腎髒病理損害,而對血糖無影響.miRNA芯片分析結果髮現,與正常對照C57BL/6小鼠相比,20週齡KKAy小鼠腎小毬內10箇miRNA的錶達上調；12箇miRNA的錶達下調.與KKAy非治療組小鼠相比,20週齡氯沙坦治療組KKAy小鼠腎小毬內共有4箇miRNA錶達下調,其中miR-503和miR-181d在KKAy非治療組小鼠腎小毬內的錶達顯著上調,氯沙坦治療可抑製其過錶達.結論 miR-503和miR-181d在糖尿病KKAy小鼠腎小毬內的錶達顯著上調,氯沙坦治療可抑製其在糖尿病狀態下的異常錶達,可能為糖尿病腎病新的治療靶點.
목적 분석당뇨병신병(DN)발병과정중신소구miRNA표체보적변화,관찰혈관긴장소수체길항제(ARB)록사탄대DN신소구miRNA표체보적영향,학인재DN발병과정중발휘관건작용적miRNA.방법 8주령KKAy소서수궤분위양사탄치료조(10 mg·kg-1·d-1)화비치료조,C57BL/6소서작위정상대조조.우20주령검측체질량、수궤혈당、뇨미량백단백、뇨기항,관찰신장형태개변.응용자주관주법분리신소구,제취총RNA,응용Affymetrix GeneChip miRNA심편,분석KKAv소서신소구microRNA표체보적변화,이급록사탄대microRNA표체보적영향.결과 KKAy소서적체질량화혈당교정상대조C57BL/6조소서현저승고(균P＜ 0.05),록사탄치료현저개선2형당뇨병KKAy소서적뇨백단백/기항비치[( 539.71±100.23) mg/g비(728.00±177.19) mg/g,P＜0.05]화신장병리손해,이대혈당무영향.miRNA심편분석결과발현,여정상대조C57BL/6소서상비,20주령KKAy소서신소구내10개miRNA적표체상조；12개miRNA적표체하조.여KKAy비치료조소서상비,20주령록사탄치료조KKAy소서신소구내공유4개miRNA표체하조,기중miR-503화miR-181d재KKAy비치료조소서신소구내적표체현저상조,록사탄치료가억제기과표체.결론 miR-503화miR-181d재당뇨병KKAy소서신소구내적표체현저상조,록사탄치료가억제기재당뇨병상태하적이상표체,가능위당뇨병신병신적치료파점.
Objective To identify susceptible miRNAs for the pathogenesis of diabetic nephropathy (DN) and the molecular targets of losartan treatment. Methods The 8-week age KKAy mice were divided into losartan treatment group (10 mg· kg-1· d-1) and non-treatment group,C57BL/6 mice were used as the control group.At age of 20 weeks,body weight,random blood glucose,urinary albumin and urinary creatinine were tested,and kidney morphology was observed.Glomeroli were separated by magnetic beads perfusion,and total RNA were extracted.MiRNAs expression profiles were analyzed by the Affymetrix GeneChip miRNAs arrays. Results At age of 20 weeks,KKAy mice developed higher body weight,higher blood glucose and higher urinary microalbumin creatinine ratio than C57BL/6 mice,and the glomerular basement membrane thickened,mesangial matrix widened.Losartan treatment markedly improved the level of urinary albumin creatinine ratio [(539.71±100.23) mg/g vs (728±177.19) mg/g,P＜0.05)] and pathological lesion of KKAy mice.The miRNA array analysis showed that there were 22 miRNAs differentially expressed between KKAy non-treatment mice and C57BL/6 mice glomeruli at age of 20 weeks.Among them,10 miRNAs were up-regulated,and 12 miRNAs were down-regulated.The expression of 4 miRNAs was down-regulated in glumeruli of KKAy mice treated by losartan compared with that of non-treatment mice.The expressions of miRNA-503 and miRNA-181d were significantly up-regulated in the glumeruli of KKAy mice and inhibited by losartan treatment, Conclusion The expressions of miRNA-503 and miRNA-181d are significantly up-regulated in the glumeruli of KKAy mice and inhibited by losartan treatment,which may be new therapeutic targets of DN.
