中暑死法医学鉴定分子标志物研究现状及进展

doi:10.3969/j.issn.1671-2072.2025.04.004

摘要/Abstract

摘要： 近年来，世界范围内极端高温天气频发，中暑死亡人数明显增加。而中暑死尸体解剖和组织病理学检查缺乏具有典型诊断价值的征象，主要表现为内部脏器缺血或淤血水肿、神经细胞坏死等非特异性改变，因此中暑死的法医学鉴定难度较大。随着对中暑死研究的深入，利用死后生化检测、免疫组织化学、红外光谱等技术寻找中暑死鉴定标志物的研究不断取得进展。通过总结目前中暑死法医学鉴定研究现状，并按照器官系统对近年来中暑死诊断分子标志物研究进展进行综述，以期为中暑死的法医学鉴定提供参考。

关键词: 法医病理学, 生物标志物, 中暑死, 死因鉴定

Abstract: In recent years, extreme heat events have become increasingly frequent worldwide, leading to a significant rise in heatstroke-related mortality. However, the autopsy and histological examinations of heatstroke deaths exhibit nonspecific findings, such as ischemia, congestion, edema of internal organs, and neuronal necrosis. These factors pose substantial challenges to the forensic determination of such cases. With advancements in research, postmortem biochemical analysis, immunohistochemistry, and infrared spectroscopy have shown promise in identifying diagnostic markers for heatstroke deaths. This review discusses the current state of forensic determination of heatstroke deaths, and summarizes recent progress of diagnostic markers based on organ systems. The aim is to provide new insights and references for the forensic diagnosis of heatstroke-related deaths.

Key words: forensic pathology, biomarker, heatstroke-related death, cause of death determination

中图分类号:

刘慧讷, 潘美辰, 孙天迎, 马楚雄, 朱玮玮, 董红梅. 中暑死法医学鉴定分子标志物研究现状及进展[J]. 中国司法鉴定, 2025(4): 40-54.

LIU Huine, PAN Meichen, SUN Tianying, MA Chuxiong, ZHU Weiwei, DONG Hongmei. Current Status and Advances of Molecular Biomarkers for Forensic Identification of Heatstroke Deaths[J]. Chinese Journal of Forensic Sciences, 2025(4): 40-54.

参考文献

[ 1 ] 葛均波，徐永健，王辰. 内科学[M]. 9版. 北京：人民卫生出版社，2018.
[ 2 ] BOUCHAMA A，ABUYASSIN B，LEHE C，et al. Classic and exertional heatstroke[J]. Nature Reviews Disease Primers，2022，8（1）：8.
[ 3 ] 丛斌. 法医病理学[M]. 5版. 北京：人民卫生出版社，2016.
[ 4 ] 陈丽，宫志敏，应圣洁，等. 2013—2018年上海市闵行区高温中暑与高温热浪的关系[J]. 上海预防医学，2021，33（8）：726-731.
[ 5 ] 张微，冯杨荣，柴树人. 2020—2024年宁波市重症中暑病例特征分析[J]. 中国公共卫生管理，2025，41（1）：140-142.
[ 6 ] 陈非儿，东春阳，张江华，等. 2013—2023年热浪对上海居民中暑的影响[J]. 环境与职业医学，2024，41（6）：610-616.
[ 7 ] 王志刚，张育萍，李娜，等. 2018—2021年张家港市高温中暑病例流行病学特征及与气象因子的关系[J]. 职业与健康，2024，40（11）：1513-1517.
[ 8 ] KENNEY W L，CRAIGHEAD D H，ALEXANDER L M. Heat waves，aging，and human cardiovascular health[J]. Medicine and Science in Sports and Exercise，2014，46（10）：1891-1899.
[ 9 ] BOUCHAMA A，DEHBI M，MOHAMED G，et al. Prognostic factors in heat wave related deaths：A meta-analysis[J]. Archives of Internal Medicine，2007，167（20）：2170-2176.
[10] FORSYTH N，SOLAN T. It’s getting hot in here：Heat stroke in children and young people for paediatric clinicians[J]. Paediatrics and Child Health，2022，32（12）：471-475.
[11] EPSTEIN Y，YANOVICH R. Heatstroke[J]. The New England Journal of Medicine，2019，380（25）：2449-59.
[12] ZHOU Y W，LI L，LIU L，et al. Heat stroke deaths caused by electric blankets：Case report and review of the literature[J]. The American Journal of Forensic Medicine and Pathology，2006，27（4）：324-327.
[13] LIU S Y，XING L，WANG Q，et al. Association between early stage-related factors and mortality in patients with exertional heat stroke：A retrospective study of 214 cases[J]. International Journal of General Medicine，2021，14：4629-4638.
[14] NIXDORF-MILLER A，HUNSAKER D M，HUNS AKER J C 3rd. Hypothermia and hyperthermia medicolegal investigation of morbidity and mortality from exposure to environmental temperature extremes[J]. Archives of Pathology & Laboratory Medicine，2006，130（9）：1297-1304.
[15] INOUE H，TSUJI A，KUDO K，et al. Pulmonary fat embolism induced by exposure to high ambient temperature in rats with a fatty liver[J]. International Journal of Legal Medicine，2005，119（5）：275-279.
[16] 胡金花，许小明，李艳红. 中暑死亡误鉴冠心病猝死 1例[J]. 南昌大学学报（医学版），2010，50（12）：99.
[17] IKEDA T，TANI N，WATANABE M，et al. Evaluation of cytokines and structural proteins to analyze the pathology of febrile central nervous system disease[J]. Legal Medicine，2021，51：101864.
[18] WANG Q，ISHIKAWA T，MICHIUE T，et al. Evaluation of human brain damage in fatalities due to extreme environmental temperature by quantification of basic fibroblast growth factor （bFGF），glial fibrillary acidic protein （GFAP），S100β and single-stranded DNA （ssDNA） immunoreactivities[J]. Forensic Science International，2012，219（1/2/3）：259-264.
[19] SHEPLEY B R，AINSLIE P N，HOILAND R L，et al. Negligible influence of moderate to severe hyperthermia on blood-brain barrier permeability and neuronal parenchymal integrity in healthy men[J]. Journal of Applied Physiology，2021，130（3）：792-800.
[20] QUAN L，ISHIKAWA T，MICHIUE T，et al. Quantitative analysis of ubiquitin-immunoreactivity in the midbrain periaqueductal gray matter with regard to the causes of death in forensic autopsy[J]. Legal Medicine，2005，7（3）：151-156.
[21] TANI N，IKEDA T，SHIDA A，et al. Postmortem water contents of major organs with regard to the cause of death[J]. Journal of Forensic and Legal Medicine，2019，65：48-54.
[22] DU Y，XU J T，JIN H N，et al. Increased cerebral expressions of MMPs，CLDN5，OCLN，ZO1 and AQPs are associated with brain edema following fatal heat stroke[J]. Scientific Reports，2017，7（1）：1691.
[23] ZHU B L，ISHIKAWA T，MICHIUE T，et al. Postmortem serum catecholamine levels in relation to the cause of death[J]. Forensic Science International，2007，173（2/3）：122-129.
[24] ISHIKAWA T，QUAN L，MICHIUE T，et al. Postmortem catecholamine levels in pericardial and cerebrospinal fluids with regard to the cause of death in medicolegal autopsy[J]. Forensic Science International，2013，228（1/2/3）：52-60.
[25] ISHIKAWA T，INAMORI-KAWAMOTO O，QUAN L，et al. Postmortem urinary catecholamine levels with regard to the cause of death[J]. Legal Medicine，2014，16（6）：344-349.
[26] ISHIKAWA T，YOSHIDA C，MICHIUE T，et al. Immunohistochemistry of catecholamines in the hypothalamic-pituitary-adrenal system with special regard to fatal hypothermia and hyperthermia[J]. Legal Medicine，2010，12（3）：121-127.
[27] ISHIKAWA T，QUAN L，LI D R，et al. Postmortem biochemistry and immunohistochemistry of adrenocorticotropic hormone with special regard to fatal hypothermia[J]. Forensic Science International，2008，179（2/3）：147-151.
[28] LIN H C，DENG K F，ZHANG J，et al. Biochemical detection of fatal hypothermia and hyperthermia in affected rat hypothalamus tissues by Fourier transform infrared spectroscopy[J]. Bioscience Reports，2019，39（3）：BSR 20181633.
[29] YOSHIDA C，ISHIKAWA T，MICHIUE T，et al. Postmortem biochemistry and immunohistochemistry of chromogranin A as a stress marker with special regard to fatal hypothermia and hyperthermia[J]. International Journal of Legal Medicine，2011，125（1）：11-20.
[30] QUAN L，ISHIKAWA T，HARA J，et al. Postmortem serotonin levels in cerebrospinal and pericardial fluids with regard to the cause of death in medicolegal autopsy[J]. Legal Medicine，2011，13（2）：75-78.
[31] ZHU B L，ISHIKAWA T，MICHIUE T，et al. Postmortem cardiac troponin T levels in the blood and pericardial fluid. Part 1. Analysis with special regard to traumatic causes of death[J]. Legal Medicine，2006，8（2）：86-93.
[32] ZHU B L，ISHIKAWA T，MICHIUE T，et al. Postmortem cardiac troponin I and creatine kinase MB levels in the blood and pericardial fluid as markers of myocardial damage in medicolegal autopsy[J]. Legal Medicine，2007，9（5）：241-250.
[33] DERVIŠEVIĆ E，HASIĆ S，KATICA M，et al. Heat-related biomarkers：Focus on the correlation of troponin I and 70 kDa heat shock protein[J]. Heliyon，2023，9（4）：e14565.
[34] ZHU B L，ISHIKAWA T，MICHIUE T，et al. Postmortem pericardial natriuretic peptides as markers of cardiac function in medico-legal autopsies[J]. International Journal of Legal Medicine，2007，121（1）：28-35.
[35] CHEN J H，MICHIUE T，ISHIKAWA T，MAEDA H. Molecular pathology of natriuretic peptides in the myocardium with special regard to fatal intoxication，hypothermia，and hyperthermia [J]. International Journal of Legal Medicine，2012，126（5）：747-56.
[36] CHEN J H，INAMORI-KAWAMOTO O，MICHIUE T，et al. Cardiac biomarkers in blood，and pericardial and cerebrospinal fluids of forensic autopsy cases：A reassessment with special regard to postmortem interval[J]. Legal Medicine，2015，17（5）：343-350.
[37] TAKASU S，MATSUMOTO S，KANTO Y，et al. Relationship between N-terminal pro-brain natriuretic peptide concentration and heart-type fatty acid-binding protein in postmortem urine[J]. Legal Medicine，2024，70：102479.
[38] HISAMURA W，TAKASU S，IWADATE K. Usefulness of heart-type fatty acid-binding protein measurement in postmortem urine specimens[J]. The American Journal of Forensic Medicine and Pathology，2024，45（1）：26-32.
[39] INOUE H，IKEDA N，TSUJI A，et al. Pulmonary fat embolization as a diagnostic finding for heat exposure[J]. Legal Medicine，2009，11（1）：1-3.
[40] LIU J，LI Q，ZOU Z M，et al. The pathogenesis and management of heatstroke and heatstroke-induced lung injury[J]. Burns & Trauma，2025，13：tkae048.
[41] FINESCHI V，D’ERRICO S，NERI M，et al. Heat stroke in an incubator：An immunohistochemical study in a fatal case[J]. International Journal of Legal Medicine，2005，119（2）：94-97.
[42] WEGNER A，DOBERENTZ E，MADEA B. Death in the sauna-vitality markers for heat exposure[J]. International Journal of Legal Medicine，2021，135（3）：903-908.
[43] INOUE H，NAKAGAWA Y，IKEMURA M，et al. Mole-cular-biological analysis of acute lung injury （ALI） induced by heat exposure and/or intravenous administration of oleic acid[J]. Legal Medicine，2012，14（6）：304-308.
[44] WANG Q，ISHIKAWA T，MICHIUE T，et al. Molecular pathology of pulmonary edema in forensic autopsy cases with special regard to fatal hyperthermia and hypothermia[J]. Forensic Science International，2013，228（1/2/3）：137-141.
[45] GENG Y，MA Q，LIU Y N，et al. Heatstroke induces liver injury via IL-1β and HMGB1-induced pyroptosis[J]. Journal of Hepatology，2015，63（3）：622-633.
[46] SCHLADER Z J，DAVIS M S，BOUCHAMA A. Biomarkers of heatstroke-induced organ injury and repair[J]. Experimental Physiology，2022，107（10）：1159-1171.
[47] MICHIUE T，ISHIKAWA T，KAWAMOTO O，et al. Postmortem serum levels of amylase and gamma glutamyl transferase （GGT） as markers of systemic tissue damage in forensic autopsy[J]. Legal Medicine，2013，15（2）：79-84.
[48] WANG Z J，TUO Y，LI B，et al. Preliminary study on fatal hyperthermia in rat liver tissue by fourier transform infrared microspectroscopy[J]. Australian Journal of Forensic Sciences，2017，49（4）：468-478.
[49] YIN X Y，WANG W. Predictive value of serum myoglobin and lactate dehydrogenase in rhabdomyolysis-induced acute kidney injury from severe heatstroke[J]. American Journal of Translational Research，2024，16（4）：1477-1483.
[50] ZHU B L，ISHIDA K，QUAN L，et al. Postmortem serum uric acid and creatinine levels in relation to the causes of death[J]. Forensic Science International，2002，125（1）：59-66.
[51] ZHU B L，ISHIKAWA T，MICHIUE T，et al. Differences in postmortem urea nitrogen，creatinine and uric acid levels between blood and pericardial fluid in acute death[J]. Legal Medicine，2007，9（3）：115-122.
[52] ZHU B L，ISHIKAWA T，MICHIUE T，et al. Evaluation of postmortem urea nitrogen，creatinine and uric acid levels in pericardial fluid in forensic autopsy[J]. Legal Medicine，2005，7（5）：287-292.
[53] WANG Q，MICHIUE T，ISHIKAWA T，et al. Combined analyses of creatine kinase MB，cardiac troponin I and myoglobin in pericardial and cerebrospinal fluids to investigate myocardial and skeletal muscle injury in medicolegal autopsy cases[J]. Legal Medicine，2011，13（5）：226-232.
[54] ABE H，YAJIMA D，HOSHIOKA Y，et al. Myoglobinemia markers with potential applications in forensic sample analysis：Lipid markers in myoglobinemia for postmortem blood[J]. International Journal of Legal Medicine，2017，131（6）：1739-1746.
[55] ISHIKAWA T，ZHU B L，LI D R，et al. Immunohistochemical investigation of ubiquitin and myoglobin in the kidney in medicolegal autopsy cases[J]. Forensic Science International，2007，171（2/3）：136-141.
[56] 王志军，申山山，邓恺飞，等. 高温环境下死亡大鼠肾傅里叶显微红外光谱变化[J]. 法医学杂志，2015，31（4）：257-261.
[57] FUJITA M Q，ZHU B L，ISHIDA K，et al. Serum C-reactive protein levels in postmortem blood—An analysis with special reference to the cause of death and survival time[J]. Forensic Science International，2002，130（2/3）：160-166.
[58] MAEDA H，ZHU B L，BESSHO Y，et al. Postmortem serum nitrogen compounds and C-reactive protein levels with special regard to investigation of fatal hyperthermia[J]. Forensic Science Medicine and Pathology，2008，4（3）：175-180.
[59] ISHIKAWA T，HAMEL M，ZHU B L，et al. Comparative evaluation of postmortem serum concentrations of neopterin and C-reactive protein[J]. Forensic Science International，2008，179（2/3）：135-143.
[60] NISHIO H，SUZUKI K. Three cases of suspected hyperthermia with remarkable elevation of serum mast cell tryptase[J]. Forensic Science International，2005，149（1）：51-55.
[61] LI D R，QUAN L，ZHU B L，et al. Evaluation of postmortem calcium and magnesium levels in the pericardial fluid with regard to the cause of death in medicolegal autopsy[J]. Legal Medicine，2009，11：S276-S278.
[62] KAWAMOTO O，MICHIUE T，ISHIKAWA T，et al. Comprehensive evaluation of pericardial biochemical markers in death investigation[J]. Forensic Science International，2013，224（1/2/3）：73-79.
[63] INGHAM A I，BYARD R W. The potential significance of elevated vitreous sodium levels at autopsy[J]. Journal of Forensic and Legal Medicine，2009，16（8）：437-440.
[64] THIERAUF A，MUSSHOFF F，MADEA B. Post-mortem biochemical investigations of vitreous humor[J]. Forensic Science International，2009，192（1/2/3）：78-82.
[65] CHEN J H，MICHIUE T，INAMORI-KAWAMOTO O，et al. Comprehensive investigation of postmortem glucose levels in blood and body fluids with regard to the cause of death in forensic autopsy cases[J]. Legal Medicine，2015，17（6）：475-482.
[66] LIN H C，ZOU D H，LUO Y W，et al. Postmortem diagnosis of fatal hypothermia hyperthermia by spectrochemical analysis of plasma[J]. Forensic Science Medicine and Pathology，2019，15（3）：332-341.
[67] TUO Y，ZHANG K，WANG L，et al. Characterization and postmortem diagnosis of fatal heatstroke using Attenuated Total Reflectance Fourier transform infrared spectroscopy combined with chemometrics[J]. Spectroscopy Letters，2020，53（5）：372-382.
[68] CIOFFI A，CECANNECCHIA C，BALDARI B，et al. Fatal heat stroke：A case report and literature review[J]. Forensic Sciences，2024，4（3）：417-431.

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