單株抗體腎臟損傷分子-1(KIM-1)在鑑別死後自溶和急性腎小管壞死之評估

Evaluation of the effect of monoclonal antibody KIM-1 in differentiating between postmortem autolysis and acute tubular necrosis

梁育瑞(Yu-Ray Liang)

指導教授 ： 孫家棟

國立臺灣大學/醫學院/法醫學研究所/碩士(2017年)

https://doi.org/10.6342/NTU201701571

摘要

急性腎小管壞死的表現存在於許多病態生理致病因素，其中懷疑毒藥物中毒所造成急性腎衰竭最具診斷上的意義，且有助於刑事偵查上的幫助。屍體的分解啟始於個體的死亡，特別是發生死後自溶時，可能會影響司法解剖中急性腎小管壞死的組織病理之判定。因此，需要有其他可用於輔助診斷的分子病理標記來鑑別急性腎小管壞死與死後自溶。其中腎臟損傷分子-1(KIM-1)為第一型穿膜醣蛋白，可作為細胞修復及再生的媒介因子。當腎臟受到缺血或藥物所致的急性腎臟損傷時，其表現量會快速地大幅增加，亦能利用免疫組織化學染色來偵測其於腎臟組織內的表現。本研究透過法醫解剖實務案例的呈現，收集6件外觀未明顯腐敗、並經組織病理診斷存在有急性腎小管壞死案例，以及6件外觀檢查可觀察到早期腐敗情況之案例。觀察其腎臟內組織病理型態的變化，且欲評估利用KIM-1單株抗體鑑別死後自溶與急性腎小管壞死之價值。結果顯示，在未明顯腐敗的案例中，可觀察到不明顯或部分自溶現象，此外有腎小管上皮破裂與腎小管上皮螺旋等特徵；而在早期腐敗的案例中，腎臟組織內皆呈明顯死後自溶現象，急性腎小管壞死的特徵則相對不明顯。在免疫組織化學染色中，所有案例皆有KIM-1的陽性表現。KIM-1主要表現於細胞質，而部分案例內表現於細胞膜(案例三)、細胞殘骸(案例三)及細胞核內(案例一、四)。然而，在早期腐敗的案例內，KIM-1則僅表現於部分腎小管中的細胞殘骸內。由研究結果可知，當發生死後自溶時，利用免疫組織化學染色法偵測KIM-1蛋白的表現，初步結果顯示其可輔助傳統的組織病理檢查，更為精確地標示出急性腎小管壞死之存在。

關鍵字

急性腎小管壞死 ； 自溶 ； 免疫組織化學染色 ； 腎臟損傷分子-1 ； 組織病理學

並列摘要

The presence of acute tubular necrosis has many pathophysiologic etiological factors. Among them, suspected drug-induced intoxication associated acute renal failure is especially worth noting and have significant influence in crime investigation. Decomposition, especially autolysis, begins from somatic death, which may mask the histopathologic diagnosis of acute tubular necrosis in forensic autopsied examination. So, useful diagnostic biomarkers would be required to differentiate acute tubular necrosis from autolysis. Kidney injury molecule-1(KIM-1) is a type I transmembrane glycoprotein as a mediator of cell recovery and regeneration. The expression of KIM-1 proteins is increased rapidly in the injured renal tissues under ischemic or toxic conditions. Also, immunohistochemistry could be used to recognize the expression of KIM-1 in injured renal tissues. In this study, we collected 6 victims who were histopathologically diagnosed to have acute tubular necrosis without apparent decomposition and 6 victims with early decomposition. We analyzed morphological changes in renal tissues, and assess the effect of monoclonal antibody KIM-1 in all subjects via immunohistochemical staining. Results showed that the H&E stain revealed subtle or partial autolysis, tubulorrhexis and tubular epithelial whorls in cases without apparent external decomposition. Autolysis was more common noticed in the cases with early decomposition which was hard to identify the acute tubular necrosis or not. Immunohistochemical analysis, positive reactions of KIM-1 protein were seen in all collected cases. The location of KIM-1 was expressed mainly in cytoplasm, and occasionally on cell membrane (case 3), in cell debris (case 3) or even in nucleus (case 1, 4). However, in cases with early decomposition, the positive reactions of KIM-1 were seen scattered in cell debris. Preliminary results reveal that detecting the expression of KIM-1 protein could assist regular histopathological examination in diagnosing the existence of acute tubular necrosis.

並列關鍵字

acute tubular necrosis ； autolysis ； immunohistochemistry ； KIM-1 ； histopathology

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