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作 者:王焕[1] 尤冠巧[2] 郭利芹 徐可[1] 冯衍生 Wang Huan;You Guanqiao;Guo Liqin;Xu Ke;Feng Yansheng(Department of Nephrology,Xinxiang Central Hospital,Xinxiang,Henan 453000,China;Department of Nephrology,Henan Provincial People’s Hospital,Zhengzhou,Henan 450003,China)
机构地区:[1]新乡市中心医院肾内科,453000 [2]河南省人民医院肾内科,郑州450003 [3]新乡医学院药学院,453000
出 处:《中华医学遗传学杂志》2021年第10期1017-1020,共4页Chinese Journal of Medical Genetics
基 金:河南省医学科技攻关计划(201503150)。
摘 要:目的探讨长链非编码RNA Gm15645在糖尿病肾病足细胞损伤小鼠中的表达及其影响。方法将C57BLKs/Jdb/db小鼠(2型糖尿病小鼠)及同窝出生的db/m小鼠(健康小鼠)随机分组。将注射带有足细胞特异性标记NPHS2的lncRNAGm15645 shRNA慢病毒的db/db小鼠作为研究组,注射生理盐水的db/db小鼠作为空白组,注射无义慢病毒的db/db小鼠作为对照组;注射带有NPHS2标记的lncRNAGm15645慢病毒的db/m小鼠作为研究组,注射生理盐水的db/m小鼠作为空白组,注射无义慢病毒的db/m小鼠作为对照组。比较各组小鼠的PAS染色结果、肾组织结构变化、GSK-3β的相对表达量以及足细胞标记蛋白podocin的表达水平。结果过表达慢病毒组小鼠过表达lncRNAGm15645,podocin表达下调,且系膜细胞和基质增生增多,基底膜明显增厚,足突广泛融合,出现足细胞损伤。db/db研究组的Gm15645表达低于db/db空白组、db/db对照组(P<0.05),podocin的表达高于db/db空白组、db/db对照组(P<0.05)。Gm15645与podocin在肾组织中共染,靶基因为GSK-3β。结论lncRNAGm15645可作为糖尿病肾病足细胞损伤的早期标志,其机制可能为GSK-3β基因的反馈调节作用。Objective To explorethe influence of long non-coding(lnc)RNA Gm15645 on the podocyte injury in mice with diabetic nephropathy.Methods Male db/db mice(with Type 2 diabetes)with a genetic background of C57BLKs/J and db/m mice(healthy)born in littermates were randomly divided into three groups.db/db group was injected with lncRNAGm15645 shRNA lentivirus with a podocyte-specific marker NPHS2;db/db blank group was injected with saline,and db/db control group was injected withnon-sense lentivirus.The results of PAS staining,pathological changes of renal tissue,relative expression of GSK-3β,and podocin expression were compared.Results lncRNAGm15645 was overexpressed and podocin was down-regulated in the lentivirus overexpressed group.Mesangial cell proliferation,mesangial matrix hyperplasia,thickened basement membrane,widely fused foot process,and podocyte injury were observed by PAS staining.The expression of Gm15645 in the db/db group was significantly lower than that of the db/db blank group and db/db control group(P<0.05),while the expression of podocin was higher(P<0.05).Gm15645 was co-stained with podocin in renal tissue,and the target gene was GSK-3β.Conclusion lncRNAGm15645 may provide an early biomarker for the occurrence of podocyte injury in diabetic nephropathy.The mechanism may be related to the feedback regulation of GSK-3βgene.
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