慢性肾脏病患者血清HIF-1α的表达及临床意义

杨树云; 吉敏; 赵文喜; 李晓娜; 李芮; 沈待羽; 孙紫娟; 赏石丽; 陈靖珊; 李俊

doi:10.12259/j.issn.2095-610X.S20210136

慢性肾脏病患者血清HIF-1α的表达及临床意义

doi: 10.12259/j.issn.2095-610X.S20210136

1.
昆明医科大学第一附属医院肾内科，云南昆明　650032
2.
镇雄县人民医院肾内科，云南镇雄　657200
3.
楚雄州医院肾内科，云南楚雄　675000
4.
云南省第三人民医院肾内科，云南昆明　650011

基金项目: 云南省科技厅-昆明医科大学应用基础研究联合专项基金资助项目[2017FE467（-041）]；昆明医科大学教研教改基金资助项目（2018-JY-Y-041）

详细信息

作者简介:
杨树云（1994～），女，云南普洱人，在读硕士研究生，主要从事肾脏病研究和临床工作

通讯作者:
李俊，E-mail： 1418411108@qq.com

中图分类号: R692.5
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出版历程
- 收稿日期: 2020-11-24
- 刊出日期: 2021-01-25

Expression and Significance of Serum HIF-1α in Patients with Chronic Kidney Disease

1.
Dept.of Nephrology，The 1st Affiliated Hospital of Kunming Medical University，Kunming Yunnan 650032
2.
Dept.of Nephrology，The People’s Hospital of Zhengxiong County，Zhengxiong Yunnan 657200
3.
Dept.of Nephrology，The People’s Hospital of Chuxiong Prefecture，Chuxiong Yunnan 675000
4.
Dept.of Nephrology，The 3rd Hospital of Yunnan Province，Kunming Yunnan 650011，China

摘要

摘要: 目的研究慢性肾脏病（chronic kidney disease，CKD）患者血清中的缺氧诱导因子-1α（hypoxia inducible factors-1α，HIF-1α）的表达情况，分析其与血清纤维化指标Ⅲ型前胶原氨基末端肽（type Ⅲprocollagen amino terminal peptide，PⅢNP）、CKD患者临床指标的关系，探讨HIF-1α在CKD中的临床应用价值。方法随机抽取63例CKD患者为研究对象，根据CKD分期对研究对象进行分组，CKD1～2期30例患者为A组，CKD3期17例患者为B组，CKD4～5期16例患者为C组，ELISA法检测入组患者血清中HIF-1α及PⅢNP的表达，同时收集入组患者的临床资料，包括姓名、性别、年龄、血常规、肝功能、肾功能、离子、24 h尿蛋白。结果 HIF-1α与PⅢNP、血肌酐（serum creatinine，Scr）、血尿素氮（blood urea nitrogen，BUN）、γ-谷氨酰转肽酶（γ-glutamyltranspeptidase，γ-GT）呈正相关（P < 0.05），而与肾小球滤过率（glomerular filtration rate，GFR）、血红蛋白（hemoglobin，HB）、血钙呈负相关（ P < 0.05），与中性粒细胞与淋巴细胞比值（neutropil-to-lymphocyte ratio，NLR）、血小板与淋巴细胞比值（platelet-to-lymphocyte ratio，PLR）、白蛋白（albumin，ALB）、血磷、24 h尿蛋白无相关性（ P > 0.05）。结论 HIF-1α与血清纤维化指标PⅢNP、肾功能、CKD并发症相关，可能参与CKD疾病的进展，可作为评价CKD的指标之一。
- 慢性肾脏病 /
- HIF-1α /
- PⅢNP /
- 肾间质纤维化
Abstract: Objective To study the expression of HIF-1α in the serum of CKD patients, analyze the relationship between it and serum fibrosis index PⅢNP, and the clinical indicators of CKD patients, and explore the clinical application value of HIF-1α in CKD. Methods A total of 63 CKD patients were randomly selected as the research object, and the research objects were grouped according to the CKD stage. 30 patients in CKD1-2 were in group A, 17 patients in CKD3 were in group B, and 16 patients in CKD4-5 were in group C.ELISA method was used to detect the expression of HIF-1α and PⅢNP in the serum of the enrolled patients, and the clinical data of the enrolled patients were collected, including gender, age, blood routine, liver function, renal function, ions, and 24-hour urine protein. Results HIF-1α was positively correlated with PⅢNP, Scr, BUN, γ-GT（P < 0.05）, negatively correlated with GFR, HB, Blood calcium（ P < 0.05）, There was no correlation with NLR, PLR, ALB, Phosphorus and 24-hour urine protein（ P > 0.05）. Conclusion HIF-1α is associated with serum fibrosis indexes, renal function, CKD complications, and may be involved in the progression of CKD disease, which can be used as one of the indicators for evaluating CKD.
- Chronic kidney disease /
- HIF-1α /
- PⅢNP /
- Renal interstitial fibrosis

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表 1 A、B、C组一般资料比较（ $\bar{x}\pm s$ ）

Table 1. Comparison of general information in groups A，B and C（ $\bar{x}\pm s$ ）

指标	A组	B组	C组	F/χ²	P
年龄（岁）	44.60 ± 14.58	54.47 ± 13.94	48.54 ± 14.02	2.923	0.061
男/女	13/17	9/8	9/7	0.826	0.661

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表 2 A、B、C组HIF-1α、PⅢNP及其他临床检验结果（ $\bar{x}\pm s$ ）

Table 2. Comparison of HIF-1α and PⅢNP in groups A，B and C（ $\bar{x}\pm s$ ）

指标	A组	B组	C组	F	P
HIF-1α（pg/mL）	14.47 ± 6.50	16.03 ± 4.55	31.22 ± 10.16^#△	3.588	0.034^*
PⅢNP（ng/mL）	8.66 ± 3.12	9.77 ± 2.21	17.01 ± 4.90^#△	3.755	0.029^*
HB（g/L）	145.53 ± 19.57	131.47 ± 28.79^#	101.19 ± 20.16^#△	20.232	< 0.001 ^*
PLT（10⁹/L）	235.30 ± 70.75	249.35 ± 83.61^#	187.25 ± 47.86^△	3.690	0.031^*
NLR	1.98 ± 0.21	2.27 ± 1.05	5.08 ± 2.56	1.992	0.145
PLR	0.02 ± 0.01	0.02 ± 0.01	0.05 ± 0.03	1.893	0.160
γ-GT（IU/L）	23.75 ± 15.83	24.39 ± 15.16	25.12 ± 5.06	0.035	0.966
Ca（mmol/L）	2.24 ± 0.16	2.29 ± 0.16^#	2.05 ± 0.18^△	9.572	< 0.001 ^*
P（mmol/L）	1.10 ± 0.16	1.77 ± 0.59	2.09 ± 0.64	1.799	0.174
ALB（g/L）	37.19 ± 7.90	38.59 ± 6.97	35.96 ± 5.22	0.574	0.566
24 h尿蛋白（g/L）	1.10 ± 0.30	1.05 ± 0.28	2.18 ± 0.60	2.301	0.109
三组间比较，*P < 0.05；与A组比较， ^#P < 0.05；与B组比较， ^△P < 0.05。

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表 3 HIF-1α与实验指标相关性

Table 3. Correlation between HIF-1α and experimental indicators

指标	r	P
PⅢNP	0.98	< 0.001 ^*
SCR	0.62	< 0.001 ^*
BUN	0.49	< 0.001 ^*
GFR	−0.26	0.040^*
HB	−0.35	0.005^*
NLR	0.10	0.44
PLR	0.10	0.417
γ-GT	0.27	0.034^*
Ca	−0.26	0.042^*
P	0.08	0.529
ALB	0.08	0.529
24 h尿蛋白	0.01	0.997
*P < 0.05表示有相关性。

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参考文献(15)

[1]	Tanaka,Tetsuhiro. Expanding roles of the hypoxia-response network in chronic kidney disease[J]. Clinical and Experimental Nephrology,2016,20(6):835-844.
[2]	Eknoyan G,Lameire N,Eckardt K,et al. KDIGO 2012 clinical practice guideline for the evaluation and management of chronic kidney disease[J]. Kidney Int,2013,3(1):5-14. doi: 10.1038/kisup.2012.77
[3]	Liu M,Ning X,Li R,et al. Signalling pathways involved in hypoxia-induced renal fibrosis[J]. Journal of Cellular and Molecular Medicine,2017,21(7):1248-1259.
[4]	Li H,Jia Y,Wang Y. Targeting HIF-1α signaling pathway for gastric cancer treatment[J]. Pharmazie,2019,74(1):3-7.
[5]	Nordquist L,Friederich-Persson M,Fasching A,et al. Activation of hypoxia-inducible factors prevents diabetic nephropathy[J]. Journal of the American Society of Nephrology,2015,26(2):328-338. doi: 10.1681/ASN.2013090990
[6]	Hu J,Wang W,Zhang F,et al. Hypoxia inducible factor-1α mediates the profibrotic effect of albumin in renal tubular cells[J]. Scientific Reports,2017,7(1):15878. doi: 10.1038/s41598-017-15972-8
[7]	贺峥,张磊,金晓明. 肾纤维化发生的细胞及分子生物学机制研究进展[J].国际免疫学杂志,2016,39(5):488-492. doi: 10.3760/cma.j.issn.1673-4394.2016.05.016
[8]	侯海生,王秋艳,陈少川. 血清学指标和瞬时弹性成像技术联合诊断慢性乙型肝炎纤维化和预测肝硬化食管静脉曲张程度的价值[J].肝脏,2019,24(4):432-435.
[9]	Su Y,Gu H,Weng D,et al. Association of serum levels of laminin,type IV collagen,procollagenⅢ N-terminal peptide,and hyaluronic acid with the progression of interstitial lung disease[J]. Medicine,2017,96(18):e6617.
[10]	Fenton A,Jesky M D,Ferro C J,et al. Serum endotrophin,a type VI collagen cleavage product,is associated with increased mortality in chronic kidney disease[J]. Plos One,2017,12(4):e0175200. doi: 10.1371/journal.pone.0175200
[11]	Baumann B,Hayashida T,Liang X,et al. Hypoxia-inducible factor-1α promotes glomerulosclerosis and regulates COL1A2 expression through interactions with Smad3[J]. Kidney International,2016,90(4):797-808. doi: 10.1016/j.kint.2016.05.026
[12]	Fassett R G,Robertson I K,Ball M J,et al. Effects of atorvastatinon oxidative stress in chronic kidney disease[J]. Nephrology,2015,20(10):697-705.
[13]	Uçar H,Gür M,Gözükara M Y,et al. Gamma glutamyltransferase activity is independently associated with oxidative stress rather than SYNTAX score[J]. Scandinavian Journal of Clinical and Laboratory Investigation,2015,75(1):7-12.
[14]	Koury M J,Haase V H. Anemia in kidney disease:harnessing hypoxia responses for therapy[J]. Nature Reviews Nephrology,2015,11(7):394. doi: 10.1038/nrneph.2015.82
[15]	Souma T,Nezu M,Nakano D,et al. Erythropoietin synthesis in renal myofibroblasts is restored by activation of hypoxia signaling[J]. Journal of the American Society of Nephrology,2016,27(2):428-438.

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