Role of high mobility group box - 1 protein in pathogenesis of acute kidney injury induced by heat stroke in mice
10.3760/cma.j.issn.1001-7097.2019.06.007
- VernacularTitle:高迁移率族蛋白1在小鼠热射病相关急性肾损伤发病机制中的意义
- Author:
Weihua WU
1
;
Liang CAI
;
Wenfei DING
;
Yuan LI
;
Wei ZHANG
;
Zheng JIANG
;
Lichao GAO
;
Jiang LIU
;
Santao OU
;
Jian LIU
Author Information
1. 西南医科大学附属医院肾病内科/四川省肾脏疾病临床医学研究中心
- Keywords:
Heat stroke;
Metabolomics;
High mobility group proteins;
Advanced glycosylation end product-specific receptor;
Acute kidney injury;
Mitochondria
- From:
Chinese Journal of Nephrology
2019;35(6):441-449
- CountryChina
- Language:Chinese
-
Abstract:
Objective To observe the differential expression of high mobility group box - 1 protein (HMGB1) in renal tissues of heat stroke mice models, and to explore its role in the pathogenesis of heat stroke associated acute kidney injury(HS-associated AKI). Methods According to random number table, 20 healthy male C57BL/6J mice were randomly divided into 2 groups, including normal control (n=10) and heat stroke group (n=10). The mice in heat stroke group were given with a 2-hour-exposure in biological simulation chamber (temperature 41℃, humidity 70％). Heat stroke was defined as anal temperature lasting more than 40 degrees Celsius. A 18F - deoxyglucose nuclide labeled vivo imaging was conducted with micro - positron emission tomography(PET)/computer tomography (CT). Serum creatinine was examined with blood example. In order to evaluate the pathological changes, HE stain was conducted with kidney tissue, and mitochondrial morphological changes in kidney tissue were observed by transmission electron microscopy. The expressions of HMGB1 and apoptosis inducing factor mitochondria associated 2 (Aifm2) were examined by immunohistochemical method, and the levels of HMGB1 and RAGE were examined by Western blotting. The cell apoptosis of renal tissue was detected by terminal deoxynucleotidyl transferase -mediated dUTP - biotin nick end labeling assay (TUNEL). The metabolomics of kidney tissue in mice were detected by liquid chromatography - mass spectrometry (LC - MS), and the pathway enrichment analysis was carried out by KEEG database. Results (1) The body temperature of the mice in heat shock group was significantly higher than that in normal control group 45 min after model establishment (P＜0.05). The level of serum creatinine in heat shock group was significantly higher than that in normal control group (P＜0.05), and the levels of 18F - deoxyglucose increased in skeletal muscle and visceral tissue of the mice in heat - shock group. (2) HE staining showed hemorrhage in collecting duct and tubular endothelial cell swelling, and mitochondrial swelling and deformation were observed by transmission electron microscopy in kidney tissue of the heat shock group. (3) Immunohistochemical method showed that the levels of Aifm2 and HMGB1 in heat shock group were higher (P＜0.05). (4) Western blotting showed that the levels of HMGB1 and RAGE in heat shock group were higher than those in normal control group (P＜0.05). (5) TUNEL showed that the number of cells with positive stain in kidney tissue of the heat shock group was higher than that in normal control group (P＜0.05). (6) Between normal control group and heat shock group, 136 differential metabolites were detected in kidney tissues. After analysis by KEGG database, pathway abnormalities such as unsaturated fatty acid metabolism disorder may be associated with HS - associated AKI, and many differential metabolites such as adrenic acid may be important regulatory points in the pathogenesis. Conclusion Acute kidney injury is a common complication of heat shock. It may be related to the dysfunction of renal mitochondria and activation of apoptotic pathway caused by systemic hypercatabolism, which may be related to the disorder of unsaturated fatty acid metabolism and activation of HMGB1. Some differential metabolites may be of high value in HS- associated AKI studies.
