Hepatology: 脂蛋白Z(LP-Z)是一种新型肝毒性脂蛋白,可以预测酒精性肝炎的疾病预后

2021-11-30 MedSci原创 MedSci原创

脂蛋白(lipoprotein)是一类由富含固醇脂、甘油三酯的疏水性内核和由蛋白质、磷脂、胆固醇等组成的外壳构成的球状微粒。

在过去十年中,酒精相关性肝病 (ALD)在全世界均呈上升趋势,酒精性肝炎 (AH) 是最危险的ALD形式,死亡率高达 50%,而且ALD 已成为美国和美国肝移植的主要原因。有研究最近在存在高胆红素的个体中发现了一种异常的脂蛋白,使用核磁共振 (NMR) 检查后将该颗粒命名为脂蛋白 Z (LP-Z)。LP-Z 是一种低密度脂蛋白 (LDL) 样颗粒,携带更高含量的甘油三酯 (TG) 和游离的胆固醇 (FC),但与LDL相比,胆固醇酯 (CE) 的含量减少。

 

肝脏不仅产生循环的主要前体脂蛋白,包括极低密度脂蛋白(VLDL)和高密度脂蛋白(HDL),肝脏也是负责肝外脂蛋白的循环代谢,如卵磷脂胆固醇酰基转移酶 (LCAT) 和肝脂肪酶 (HL),也称为如脂肪酶 C 肝型 (LIPC)。因此,本项研究旨在探究LP-Z在AH的诊断、其积累的机制以及诊断和治疗意义。

 

为此,研究人员使用核磁共振波谱测量患者的血清LP-Z水平(核磁共振波谱是一种完善的临床检测方法)。与对照组(包括酗酒者和肝硬化)相比,四个AH队列中 LP-Z 的血清水平显着升高。对于Z指数的定义是由LP-Z与含载脂蛋白B的总脂蛋白的比率计算的,代表与正常极低密度脂蛋白 (VLDL) 代谢的偏差程度。高Z指数与90天死亡率相关,独立于终末期肝病模型,并提供额外的预后价值。Z-index ≤ 0.6 和 Z-index 在两周内下降 ≥ 0.1 都预测了更低的90天的存活率。肝组织的 RNAseq 分析表明,负责将VLDL 肝外转化为 LDL 和 AH 疾病严重程度的酶的表达呈负相关。为了评估LP-Z中的FC是否有助于 AH 的发病机制,研究还发现 AH 患者肝脏外植体中的 FC 水平显着改变。

 

本项研究证实AH中脂蛋白代谢受损会导致体循环中LP-Z的积累,这对过量的FC具有肝毒性。Z-index≤0.6可以预测90天存活率,而且这个指标独立于疾病预测的常规生物标志物。

原始出处:

Kunpeng Hu. Et al. Lipoprotein Z, A novel hepatotoxic lipoprotein, predicts outcome in alcoholic hepatitis. Hepatology. 2021.

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    2021-12-01 gwc384
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