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[1]汤 蜜,李沁芸,李少斌,等.含羞草素对糖尿病大鼠肾脏缺氧损伤及HIF/PHD轴的影响[J].遵义医科大学学报,2019,42(05):527-533.
 Tang Mi,Li Qinyun,Li Shaobin,et al.Effects of L-mimosine on renal hypoxia and HIF/PHD axis in diabetic rats[J].Journal of Zunyi Medical University,2019,42(05):527-533.
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含羞草素对糖尿病大鼠肾脏缺氧损伤及HIF/PHD轴的影响()
     
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《遵义医科大学学报》[ISSN:1000-9035/CN:22-1262/O4]

卷:
第42卷
期数:
2019年05期
页码:
527-533
栏目:
基础医学研究
出版日期:
2019-10-25

文章信息/Info

Title:
Effects of L-mimosine on renal hypoxia and HIF/PHD axis in diabetic rats
文章编号:
1000-2715(2019)05-0527-07
作者:
汤 蜜12 李沁芸1李少斌12颜晓勇1余丽梅12杨亦彬12
(1.遵义医科大学附属医院 肾内科,贵州 遵义 563099; 2.遵义医科大学附属医院 细胞工程实验室再生医学科,贵州 遵义 563099)
Author(s):
Tang Mi12Li Qinyun1Li Shaobin12Yan Xiaoyong1Yu Limei12Yang Yibin12
(1.Department of Nephrology,Affiliated Hospital of Zunyi Medical University,Zunyi Guizhou 563099,China; 2.Department of Regenerative Medicine,Cell Engineering Laboratory,Affiliated Hospital of Zunyi Medical University,Zunyi Guizhou 563099,China)
关键词:
糖尿病肾病 缺氧 低氧诱导因子 脯氨酸羟化酶 血红素加氧酶-1
Keywords:
diabetic nephropathy hypoxia hypoxia-inducible factor proline hydroxylase heme oxygenase-1
分类号:
R587.2
DOI:
-
文献标志码:
A
摘要:
目的 通过含羞草素干预糖尿病大鼠,探讨其对糖尿病大鼠肾脏缺氧及HIF/PHD轴的影响。方法 将SD大鼠(n=24)随机分为对照组(NC组,n=8)、糖尿病组(DN组,n=8)和含羞草素治疗组(DL组,n=8)。糖尿病模型通过腹腔注射链脲佐菌素构建。腹腔注射含羞草素(50 mg/kg/d)于成模8周后的大鼠体内。分别于12、16周采集各组尿液和血糖值,处死大鼠并摘取双肾。缺氧探针法检测缺氧情况,免疫组织化学染色和RT-PCR检测HIF/PHD轴上的缺氧诱导因子-1α(HIF-1α)、脯氨酸羟化酶2(PHD2)以及血红素加氧酶-1(HO-1)的蛋白和mRNA表达。结果 模型组和含羞草素治疗组在两时点的血糖和24 h尿蛋白值均明显高于对照组(P<0.05),DL组24h尿蛋白低于DN组(P<0.05)。DN组、DL组的肾脏均可见不同程度的肾小球增大、部分球囊扩张、系膜基质增多、肾小管扩张等,DL组病理改变相对DN组减轻。肾组织缺氧探针显示:糖尿病组和含羞草素治疗组的阳性着色面积较对照组明显扩大(P<0.05),且治疗后面积显著减小(P<0.05)。免疫组化和PCR结果显示:模型组在两时点肾脏HIF-1α、PHD2、HO-1蛋白和mRNA表达均有不同程度的上调,但16周时HO-1蛋白、HIF-1α mRNA以及两时点HO-1 mRNA表达上调差异无统计学意义,并且16周较12周时表达呈现下调趋势,而DL组两时点肾脏HIF-1α、PHD2、HO-1蛋白表达显著高于DN组(P<0.05),两时点HIF-1α以及16周HO-1 mRNA表达也显著高于DN组(P<0.05)。结论 含羞草素可缓解糖尿病大鼠肾脏缺氧状态,并能上调HIF/PHD轴上的HIF-1α、PHD2、HO-1的表达水平。
Abstract:
ObjectiveTo investigate the effect of L-mimosine intervention on renal hypoxia and HIF/PHD axis in diabetic rats.Methods SD rats were randomly divided into three groups:(i)The control group(NC,n=8),(ii)The diabetic nephropathy group(DN,n=8),where rats were intraperitoneally injected with streptozotocin(STZ),(iii)The L-mim treatment group(DL,n=8),where rats were intraperitoneally injected with L-mimosine drugs for 8 weeks after STZ injection.At 12 weeks and 16 weeks,blood samples were taken to detect blood glucose,urine output and 24-hour urine protein changes.At the same time,rats were sacrificed and kidney tissues were obtained for further analyses.Hypoxia was detected by measuring the expression changes of hypoxia inducible factor-1α(HIF-1α),proline hydroxylase 2(PHD2),and heme oxygenase-1(HO-1)through hypoxia probe,immunohistochemistry and RT-PCR.Results Blood glucose and 24-hour proteinuria were significantly increased in both DN and DL groups,but urinary protein in DL group was lower than that in DN group.There were different degrees of glomerular enlargement,partial balloon dilation,increased mesangial matrix,and tubular dilatation on kidney in DN and DL groups.The pathological changes in DL group were relatively relieved.The hypoxic probe of the renal tissue showed positive in DN and DL groups.The coloration was significantly increased,but the positive staining degree and area of DL group were lower than those of DN group.Compared with NC group,DN group had two time points of kidney HIF-1α,PHD2 and HO-1 protein expressions.The expressions of protein and mRNA were adjusted to different degrees,but there was no statistically significant up-regulation of HO-1 protein,HIF-1α mRNA and HO-1 mRNA expression at two weeks.The expressions of HIF-1α,PHD2 and HO-1 protein in DL group were significantly higher than those in DN group.The expressions of HIF-1α and 16-week HO-1 mRNA at the two time points in DL group were also significantly higher than those in DN group.Conclusion L-mimosine intervention could alleviate renal hypoxia in diabetic rats,which may be related to the up-regulation of HIF-1α,PHD2 and HO-1 expressions on the HIF/PHD axis.

参考文献/References:

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备注/Memo

备注/Memo:
[基金项目]国家自然科学基金资助项目(NO:81260118); 遵义医学院博士科研启动基金资助项目(NO:[2006]13)。 [通信作者]杨亦彬,男,博士,主任医师,硕士生导师,研究方向:糖尿病肾病,E-mail:yyb1011@sina.com。
更新日期/Last Update: 2019-10-25