肾结石患者肾乳头密度和抑制钙化相关基因表达研究

胡恒龙; 朱云鹏; 李聪; 崔磊; 卢宇超; 张加桥; 秦保龙; 王庆; 王少刚; 郭小林

doi:10.13201/j.issn.1001-1420.2020.05.001

肾结石患者肾乳头密度和抑制钙化相关基因表达研究

- 华中科技大学同济医学院附属同济医院泌尿外科(武汉, 430030)
基金项目:
国家自然科学基金项目(No:81570631,81800626)

详细信息

通讯作者: 郭小林,E-mail:guoxiaolin@tjh.tjmu.edu.cn

中图分类号: R692.4

收稿日期: 2019-10-16

Papillary density and expression of ectopic calcification inhibitors in renal stone formers

- Deparment of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China

More Information

Corresponding author: GUO Xiaolin, E-mail: guoxiaolin@tjh.tjmu.edu.cn

Received Date: 16 October 2019

摘要

摘要: 目的:Randall钙斑是位于肾乳头间质的异位钙化,被认为是草酸钙结石的起始病变。这些钙盐沉积可能源于异位钙化相关基因表达失调,并在宏观上导致肾乳头密度增加。本研究拟探究肾结石患者和非结石对照者肾乳头CT值和钙化抑制相关基因表达的差异。方法:纳入60例具有腹部CT平扫影像的肾结石患者作为结石组。选取60例具有腹部CT影像,且与结石患者年龄性别相匹配非结石患者作为对照组。每组均各纳入男40例,女20例。两组平均年龄分别为(48.67±11.14)岁和(48.40±10.73)岁。在平扫CT上测量其肾脏上盏、中盏和下盏肾乳头密度并比较。检索和下载Gene Expression Omnibus数据库Randall钙斑芯片GSE73680数据文件。分析比较5种钙化抑制相关基因包括基质Gla蛋白(MGP)、骨桥蛋白(OPN)、骨钙素(OCN)、骨保护素(OPG)和富Gla蛋白(GRP)在结石组和对照组患者肾乳头组织的表达情况。结果:结石组患者肾乳头密度均值显著高于对照组\[(49.19±7.26) HU vs.(41.11±5.55) HU\]。与对照组相比,结石组肾乳头OPN、OPG、OCN和GRP表达分别是对照组1.93倍、1.16倍、1.57倍和2.04倍,P值分别为0.52、0.58、0.06和0.08。MGP在结石患者肾乳头表达下调3.15倍(P=0.05)。结论:结石患者肾乳头密度显著增高,抑制钙化相关基因MGP表达降低。
- 肾结石 /
- Randall钙斑 /
- 肾乳头密度 /
- 基质Gla蛋白 /
- 异位钙化
Abstract: objective: Randall's plaque is a kind of interstitial calcification in the renal papillary and is considered as the nidus for renal stone. The ectopic calcification may result from the dysregulation of calcification inhibitors and increase the papillary density. The aim of this study is to compare the renal papillary density and expressions ofcalcification inhibitors between stone formers and non-stone formers. Method: Sixty upper urinary tract stone formers and 60 age and sex matched non-stone formers were included.Both the stone formers and non-stone formers group included 40 males and 20 females. The mean age of the two groups were(48.67±11.14)years and(48.40±10.73) years, respectively. All the included subjects had non-contrast abdominal CT images. The renal papillary density of upper calyx, middle calyx and lower calyx were measured and compared. The Gene Expression Omnibus(GEO) database was retrieved. The Randall's plaque chip(GSE73680) data file was downloaded and analyzed. The papillary expression of calcification inhibitors including Matrix Gla protein(MGP), osteopontin(OPN), osteocalcin(OCN), osteoprotegerin(OPG) and Gla-rich protein(GRP)were evaluated and compared between stone and non-stone formers. Result: The mean renal papillary density of the stone formers was significantly higher than that of non-stone formers\[(49.19±7.26) HU vs.(41.11±5.55) HU\]. Compared with non-stone formers, the expression levels of OPN, OPG, OCN and GRP in stone formers increased 1.93, 1.16, 1.57 and 2.04 times, with P values of 0.52, 0.58, 0.06 and 0.08, respectively. And the expression of MGP in stone formers was down-regulated by 3.15 times(P=0.05).Conclusion: The papillary density was significantly increased and MGP expression is decreased in stone formers.
- nephrolithiasis /
- Randall's plaque /
- papillary density /
- matrix gla protein /
- ectopic calcification

HTML全文

参考文献(18)

[1]	Wang W,Fan J,Huang G,et al.Prevalence of Kidney Stones in Mainland China:A Systematic Review[J].Sci Rep,2017,7:41630-41630.
[2]	Sorokin I,Mamoulakis C,Miyazawa K,et al.Epidemiology of Stone Disease across the World[J].World J Urol,2017,35(9):1301-1320.
[3]	Skolarikos A,Straub M,Knoll T,et al.Metabolic Evaluation and Recurrence Prevention for Urinary Stone Patients:Eau Guidelines[J].Eur Urol,2015,67(4):750-763.
[4]	D'Costa MR,Haley WE,Mara KC,et al.Symptomatic and Radiographic Manifestations of Kidney Stone Recurrence and Their Prediction by Risk Factors:A Prospective Cohort Study[J].J Am Soc Nephrol,2019,30(7):1251-1260.
[5]	Rodgers A,Trinchieri A,Ather MH,et al.Vision for the future on urolithiasis:research,management,education and training-some personal views[J].Urolithiasis,2019,47(5):401-413.
[6]	Coe FL,Worcester EM,Evan AP.Idiopathic Hypercalciuria and Formation of Calcium Renal Stones[J].Nat Rev Nephrol,2016,12(9):519-533.
[7]	Pearle MS,Antonelli JA,Lotan Y.Urinary Lithiasis:Etiology,Epidemiology,and Pathogenesis[M]//Wein AJ,Kavoussi LR,Partin AW,et al.Campbell-Walsh Urology,11th ed.Philadelphia:Elsevier,2016:1170-1199.
[8]	Shavit L,Girfoglio D,Kirkham A,et al.Increased renal papillary density in kidney stone formers detectable by CT scan is a potential marker of stone risk,but is unrelated to underlying hypercalciuria[J].Urolithiasis,2016,44(5):471-475.
[9]	Ciudin A,Galvez MPL,Izquierdo RS,et al.Validation of Randall's Plaque Theory Using Unenhanced Abdominal Computed Tomography[J].Urology,2013,81(2):246-249.
[10]	Ferraro PM,Vittori M,Macis G,et al.Changes in Renal Papillary Density after Hydration Therapy in Calcium Stone Formers[J].BMC Urol,2018,18(1):101.
[11]	Schurgers LJ,Uitto J,Reutelingsperger CP.Vitamin K-Dependent Carboxylation of Matrix Gla-Protein:A Crucial Switch to Control Ectopic Mineralization[J].Trends Mol Med,2013,19(4):217-226.
[12]	Caballero D,Li Y,Ponsetto J,et al.Impaired Urinary Osteopontin Excretion in Npt2a-/-Mice[J].Am J Physiol Renal Physiol,2017,312(1):F77-F83.
[13]	Icer MA,Gezmen-Karadag M.The Multiple Functions and Mechanisms of Osteopontin[J].Clin Biochem,2018,59:17-24.
[14]	Moser SC,van der Eerden BCJ.Osteocalcin-a Versatile Bone-Derived Hormone[J].Front Endocrinol(Lausanne),2018,9:794.
[15]	Rochette L,Meloux A,Rigal E,et al.The Role of Osteoprotegerin in Vascular Calcification and Bone Metabolism:The Basis for Developing New Therapeutics[J].Calcif Tissue Int,2019,105(3):239-251.
[16]	Wang Q,Hu H,Dirie NI,et al.High Concentration of Calcium Promotes Mineralization in Nrk-52e Cells Via Inhibiting the Expression of Matrix Gla Protein[J].Urology,2018,119:161 e161-161 e167.
[17]	Khan A,Wang W,Khan SR.Calcium Oxalate Nephrolithiasis and Expression of Matrix Gla Protein in the Kidneys[J].World J Urol,2014,32(1):123-130.
[18]	Jia Z,Wang S,Tang J,et al.Does Crystal Deposition in Genetic Hypercalciuric Rat Kidney Tissue Share Similarities with Bone Formation?[J].Urology,2014,83(2):509.