The Possibility of Urinary Liver-Type Fatty Acid-Binding Protein as a Biomarker of Renal Hypoxia in Spontaneously Diabetic Torii Fatty Rats

被引：16

作者：

Tanabe, Jun ^{[1
]}

Ogura, Yuji ^{[2
]}

Nakabayashi, Mikie ^{[3
]}

Nagai, Yoshio ^{[4
]}

Watanabe, Shiika ^{[1
]}

Sugaya, Takeshi ^{[1
]}

Ohata, Keiichi ^{[1
]}

Ichikawa, Daisuke ^{[1
]}

Inoue, Kazuho ^{[5
]}

Hoshino, Seiko ^{[5
]}

Kimura, Kenjiro ^{[6
]}

Shibagaki, Yugo ^{[1
]}

Ono, Yumie ^{[3
]}

Kamijo-Ikemori, Atsuko ^{[1
,5
]}

机构：

[1] St Marianna Univ, Sch Med, Dept Internal Med, Div Nephrol & Hypertens, Kawasaki, Kanagawa, Japan

[2] St Marianna Univ, Sch Med, Dept Physiol, Kawasaki, Kanagawa, Japan

[3] Meiji Univ, Sch Sci & Technol, Dept Elect & Bioinformat, Kawasaki, Kanagawa, Japan

[4] St Marianna Univ, Sch Med, Dept Internal Med, Div Metab & Endocrinol, Kawasaki, Kanagawa, Japan

[5] St Marianna Univ, Sch Med, Dept Anat, Kawasaki, Kanagawa, Japan

[6] JCHO Tokyo Takanawa Hosp, Tokyo, Japan

来源：

KIDNEY & BLOOD PRESSURE RESEARCH | 2019年 / 44卷 / 06期

基金：

日本学术振兴会;

关键词：

Diabetes; Diabetic kidney disease; Hypoxia; Kidney; Liver-type fatty acid-binding protein; Tubulointerstitial damage; TUBULOINTERSTITIAL INJURY; OXYGEN-CONSUMPTION; KIDNEY-DISEASE; RECEPTOR; HYPERGLYCEMIA; NEPHROPATHY; REFLECTS;

D O I：

10.1159/000503926

中图分类号：

Q4 [生理学];

学科分类号：

071003 ;

摘要：

Background: Renal hypoxia is an aggravating factor for tubulointerstitial damage, which is strongly associated with renal prognosis in diabetic kidney disease (DKD). Therefore, urinary markers that can detect renal hypoxia are useful for monitoring DKD. Objective: To determine the correlation between urinary liver-type fatty acid-binding protein (L-FABP) and renal hypoxia using a novel animal model of type 2 diabetes. Methods: Male spontaneously diabetic Torii (SDT) fatty rats (n = 6) were used as an animal model of type 2 diabetes. Age- and sex-matched Sprague-Dawley (SD) rats (n = 8) were used as controls. Body weight, systolic blood pressure, and blood glucose levels were measured at 8, 12, 16, and 24 weeks of age. Urine samples and serum and kidney tissues were collected at 24 weeks of age. Microvascular blood flow index (BFI) was measured using diffuse correlation spectroscopy before sampling both the serum and kidneys for the evaluation of renal microcirculation at the corticomedullary junction. Results: Obesity, hyperglycemia, and hypertension were observed in the SDT fatty rats. Focal glomerular sclerosis, moderate interstitial inflammation, and fibrosis were significantly more frequent in SDT fatty rats than in SD rats. While the frequency of peritubular endothelial cells and phosphoendothelial nitric oxide synthase levels were similar in both types of rats, the degree of renal hypoxia-inducible factor-1 alpha (HIF-1 alpha) expression was significantly higher (and with no change in renal vascular endothelial growth factor expression levels) in the SDT fatty rats. Urinary L-FABP levels were significantly higher and renal microvascular BFI was significantly lower in the SDT fatty rats than in the SD rats. Urinary L-FABP levels exhibited a significant positive correlation with renal HIF-1 alpha expression and a significant negative correlation with renal microvascular BFI. Conclusions: Urinary L-FABP levels reflect the degree of renal hypoxia in DKD in a type 2 diabetic animal model. Urinary L-FABP may thus prove useful as a renal hypoxia marker for monitoring DKD in patients with type 2 diabetes in clinical practice.

引用

页码：1476 / 1492

页数：17

共 46 条

[41] Hypertension with diabetes mellitus: significance from an epidemiological perspective for Japanese [J].

Tatsumi, Yukako ;

Ohkubo, Takayoshi .

HYPERTENSION RESEARCH, 2017, 40 (09) :795-806

[42]

Tuttle KR, 2014, AM J KIDNEY DIS, V64, P510, DOI [10.2337/dc14-1296, 10.1053/j.ajkd.2014.08.001]

[43] Urinary Level of Liver-Type Fatty Acid Binding Protein Reflects the Degree of Tubulointerstitial Damage in Polycystic Kidney Disease [J].

Watanabe, Shiika ;

Ichikawa, Daisuke ;

Sugaya, Takeshi ;

Ohata, Keiichi ;

Inoue, Kazuho ;

Hoshino, Seiko ;

Kimura, Kenjiro ;

Shibagaki, Yugo ;

Kamijo-Ikemori, Atsuko .

KIDNEY & BLOOD PRESSURE RESEARCH, 2018, 43 (06) :1716-1729

[44] Renal L-type fatty acid-binding protein in acute ischemic injury [J].

Yamamoto, Tokunori ;

Noiri, Eisei ;

Ono, Yoshinari ;

Doi, Kent ;

Negishi, Kousuke ;

Kamijo, Atsuko ;

Kimura, Kenjiro ;

Fujita, Toshiro ;

Kinukawa, Tsuneo ;

Taniguchi, Hideki ;

Nakamura, Kazuo ;

Goto, Momokazu ;

Shinozaki, Naoshi ;

Ohshima, Shinichi ;

Sugaya, Takeshi .

JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY, 2007, 18 (11) :2894-2902

[45] Urinary Excretion of Liver Type Fatty Acid Binding Protein Accurately Reflects the Degree of Tubulointerstitial Damage [J].

Yokoyama, Takeshi ;

Kamijo-Ikemori, Atsuko ;

Sugaya, Takeshi ;

Hoshino, Seiko ;

Yasuda, Takashi ;

Kimura, Kenjiro .

AMERICAN JOURNAL OF PATHOLOGY, 2009, 174 (06) :2096-2106

[46] Time-dependent blood flow and oxygenation in human skeletal muscles measured with noninvasive near-infrared diffuse optical spectroscopies [J].

Yu, GQ ;

Durduran, T ;

Lech, G ;

Zhou, C ;

Chance, B ;

Mohler, ER ;

Yodh, AG .

JOURNAL OF BIOMEDICAL OPTICS, 2005, 10 (02)

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