[1]岳晓丹,常宝成,贾俊亚,等.清醒大鼠急性高血糖模型的建立及其 “肾毒性”损伤特点及机制研究[J].国际内分泌代谢杂志,2017,37(04):227-231.
　Yue Xiaodan*,Chang Baocheng,Jia Junya,et al.The modeling of acute hyperglycemia in conscious rats and the kidney damaging characteristics and mechanism[J].International Journal of Endocrinology and Metabolism,2017,37(04):227-231.
点击复制

清醒大鼠急性高血糖模型的建立及其 “肾毒性”损伤特点及机制研究()
分享到：

《国际内分泌代谢杂志》[ISSN:1673-4157/CN:12-1383/R]

卷:
37
期数:
2017年04期
页码:
227-231
栏目:
论著
出版日期:
2017-07-20

文章信息/Info

Title:
The modeling of acute hyperglycemia in conscious rats and the kidney damaging characteristics and mechanism
作者:
岳晓丹; 常宝成; 贾俊亚; 单春艳; 朱红; 杨菊红; 郑妙艳; 杨少华; 郭振红;  徐俊; 张欣荣; 王靖宇
300070 天津医科大学代谢病医院糖尿病肾病科,内分泌研究所,卫生部激素与发育重点实验室,天津市代谢性疾病重点实验室(岳晓丹,常宝成,单春艳,杨菊红,郑妙艳,杨少华,郭振红,徐俊,张欣荣,王靖宇); 300052 天津医科大学总医院肾科(贾俊亚); 300070 天津医科大学公共卫生学院流行病与卫生统计学系(朱红)
Author(s):
Yue Xiaodan*;  Chang Baocheng;  Jia Junya;  Shan Chunyan;  Zhu Hong;  Yang Juhong;  Zheng Miaoyan;  Yang Shaohua;  Guo Zhenhong;  Xu Jun;  Zhang Xinrong;  Wang Jingyu
*Department of Diabetic Nephropathy, Key Laboratory of Hormones and Development(Ministry of Health), Tianjin Key Laboratory of Metabolic Diseases, The Metabolic Diseases Hospital & Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin 300070, China
关键词:
高糖毒性;  肾小管;  氧化应激
Keywords:
Hyperglycemic toxicity;  Renal tubule;  Oxidative stress
文献标志码:
A
摘要:
目的 建立大鼠清醒状态下急性高血糖模型,观察急性高血糖引起肾损伤的特点,并探讨其可能机制。方法 应用随机数字表法将Sprague-Dawley大鼠分为高糖组和对照组(n=10),颈静脉置管术后行高葡萄糖钳夹实验建立急性高血糖模型。术后第5天高糖组经颈静脉置管泵入50%葡萄糖溶液,使血糖维持于16～18 mmol/L; 对照组以同等速度泵入生理盐水,实验持续6 h,留取24 h尿液后处死大鼠并取材。光镜和透射电镜观察肾脏结构损伤,检测肾功能、尿微量白蛋白(UMA)及肾损伤分子-1(KIM-1)等肾损伤指标,检测超氧化物歧化酶(SOD)、丙二醛及8-羟基-2'-脱氧鸟苷(8-OHdG)评估氧化应激水平。结果 高糖组出现明显肾脏结构和功能损伤。结构上可见近曲小管细胞肿胀,细胞内线粒体肿胀、排列紊乱; 与对照组相比,高糖组24 h UMA、KIM-1及中性粒细胞明胶酶相关载脂蛋白(NGAL)均显著升高(t=-2.969、-2.220、-2.791,P均<0.05),而血清及肾组织SOD活性明显下降(t=2.537、2.599,P均<0.05),血清丙二醛、肾组织丙二醛及尿8-OHdG明显升高(t=-2.532、-2.600、-2.968,P均<0.05)。结论 成功建立大鼠急性高血糖模型。急性高血糖可导致肾脏结构和功能损伤,以肾小管损伤为主,氧化应激及线粒体损伤参与急性高血糖“肾毒性”损伤的发生、发展。
Abstract:
Objective To establish the modeling of acute hyperglycemia, observe the characteristics of acute hyperglycemia induced kidney damages, and to explore its possible mechanisms.Methods Sprague-Dawley rats were divided into hyperglycemia group and control group according to the random number table, and underwent catheterization through jugular vein before acute hyperglycemic clamp to establish the modeling of acute hyperglycemia. Rats in hyperglycemia group were infused with 50% glucose solution at the 5th day after the surgery to maintain the blood glucose between 16 and 18 mmol/L, and rats in control group were infused with normal saline for 6 hours. Then 24-hour urine was collected and the rats were killed. Renal structure alterations were observed under optical and transmission electron microscope, renal injury were evaluated by detecting renal function, urinary microalbumin(UMA)and kidney injury molecule-1(KIM-1), and oxidative stress activation were assessed by detecting superoxide dismutase(SOD), malondialdehyde(MDA)and 8-hydroxy-2'-deoxyguanosine(8-OHdG).Results The renal morphologic and functional injuries were found in hyperglycemia group, and severe damages were found in tubular epithelial cells including the enlargement of epithelial cells, the swelling and disarrangment of mitochondria of epithelial cells. Compared with control group, UMA, KIM-1, and neutrophil gelatinase-associated lipocalin(NGAL)level were increased significantly in hyperglycemia group(t=-2.969, -2.220, -2.791, all P<0.05). Moreover, compared with control group, serum and renal SOD activity were decreased(t=2.537, 2.599, all P<0.05), while serum MDA, renal MDA and urinary 8-OHdG level were increased significantly in hyperglycemia group(t=-2.532,-2.600,-2.968, all P<0.05).Conclusions The acute hyperglycemia model in healthy rats are set up successfully. Acute hyperglycemia causes significant damages of renal morphology and functions, especially to tubular epithelial cells, mitochondria injuries and oxidative stress activation may play important roles in acute hyperglycemia induced kidney injuries.

参考文献/References:

[1] Francini F, Del Zotto H, Gagliardino JJ. Effect of an acute glucose overload on islet cell morphology and secretory function in the toad[J].Gen Comp Endocrinol,2001,122(2):130-138.DOI:10.1006/gcen.2001.7617.
[2] Akhtar S, Barash PG, Inzucchi SE. Scientific principles and clinical implications of perioperative glucose regulation and control[J].Anesth Analg,2010,110(2):478-497. DOI:10.1213/ANE.0b013e3181c6be63.
[3] Tonolo G, Cherchi S. Tubulointerstitial disease in diabetic nephropathy[J].Int J Nephrol Renovasc Dis,2014,7:107-115. DOI:10.2147/IJNRD.S37883.
[4] Comper WD. Albuminuria is controlled primarily by proximal tubules[J].Nat Rev Nephrol,2014,10(3):180. DOI:10.1038/nrneph.2013.58-c1.
[5] Bonventre JV. Can we target tubular damage to prevent renal function decline in diabetes?[J].Semin Nephrol,2012,32(5):452-462. DOI:10.1016/j.semnephrol.2012.07.008.
[6] Russo LM, Sandoval RM, Campos SB,et al. Impaired tubular uptake explains albuminuria in early diabetic nephropathy[J].J Am Soc Nephrol,2009,20(3):489-494. DOI:10.1681/ASN.2008050503.
[7] Medi B, Rovcanin B, Vujovic KS,et al. Evaluation of novel biomarkers of acute kidney injury: the possibilities and limitations[J].Curr Med Chem,2016,23(19):1981-1997.
[8] Bonventre JV. Kidney injury molecule-1: a translational journey[J].Trans Am Clin Climatol Assoc,2014,125:293-299.
[9] Ren H, Zhou X, Dai D,et al. Assessment of urinary kidney injury molecule-1 and interleukin-18 in the early post-burn period to predict acute kidney injury for various degrees of burn injury[J].BMC Nephrol,2015,16:142. DOI: 10.1186/s12882-015-0140-3.
[10] Parikh CR, Coca SG, Thiessen-Philbrook H,et al. Postoperative biomarkers predict acute kidney injury and poor outcomes after adult cardiac surgery[J].J Am Soc Nephrol,2011,22(9):1748-1757. DOI:10.1681/ASN.2010121302.
[11] Khalid U, Jenkins RH, Pino-Chavez G,et al. A localized ischemic preconditioning regimen increases tumor necrosis factor α expression in a rat model of kidney ischemia-reperfusion injury[J].Exp Clin Transplant,2015,13(6):535-542.
[12] Makris K, Markou N, Evodia E,et al. Urinary neutrophil gelatinase-associated lipocalin(NGAL)as an early marker of acute kidney injury in critically ill multiple trauma patients[J].Clin Chem Lab Med,2009,47(1):79-82. DOI: 10.1515/CCLM.2009.004.
[13] Moon SJ, Park HB, Yoon SY,et al. Urinary biomarkers for early detection of recovery in patients with acute kidney injury[J].J Korean Med Sci,2013,28(8):1181-1186. DOI:10.3346/jkms.2013.28.8.1181.
[14] Gorin Y, Wauquier F. Upstream regulators and downstream effectors of NADPH oxidases as novel therapeutic targets for diabetic kidney disease[J].Mol Cells,2015,38(4):285-296. DOI:10.14348/molcells.2015.0010.
[15] Sun L, Xie P, Wada J,et al. Rap1b GTPase ameliorates glucose-induced mitochondrial dysfunction[J].J Am Soc Nephrol,2008,19(12):2293-2301. DOI:10.1681/ASN.2008030336.

备注/Memo

备注/Memo:
基金项目:国家自然科学基金资助项目(81603461,81473472,81373864); 天津市应用基础与前沿技术研究计划(15JCYBJC50300,13JCZDJC30500,17JCZDJC34700); 卫生部激素与发育重点实验室开放课题(2014DX04); 天津医科大学科学基金项目(2015KYZM03)
通信作者:王靖宇,Email: elsa_0521@163.com
更新日期/Last Update: 2017-07-30