2024年4月12日发(作者：)

α-酮戊二酸对胆汁淤积性肝损伤的

缓解作用及机制研究

摘 要

目的：探究α-酮戊二酸（α-KG）对胆汁淤积性肝损伤（BDL）

的缓解作用及其机制。

方法：将健康雄性大鼠随机分为正常对照组、BDL组和α-KG

处理组，每组8只。BDL和α-KG处理组分别采用手术方法实

施胆管结扎和每天饲喂0.5g/kgα-KG。观察治疗4周后各组

大鼠肝功能、病理学和细胞凋亡指标的变化，并检测胆汁渗漏、

TGF-β1、Smad2/3等信号通路的影响。

结果：与BDL组相比，α-KG处理组的肝功能指标如ALT、AST、

ALP等降低，肝组织病理学损伤得到缓解，细胞凋亡明显减少。

α-KG处理能够显著减少biliary leak的发生，在肝脏组织

中抑制TGF-β1信号通路并提高活化的Smad2/3的表达。

结论：α-KG可以通过调节TGF-β1/Smad信号通路、减少凋

亡细胞和减轻胆汁渗漏等多个方面发挥对BDL诱导的肝损伤的

保护作用，是一种具有潜在治疗价值的药物。

关键词：α-酮戊二酸，胆汁淤积性肝损伤，TGF-β1/Smad信

号通路，细胞凋亡，胆汁渗漏

Abstract

Objective: To explore the protective effects of α-

ketoglutarate (α-KG) against bile duct ligation

(BDL)-induced liver injury and its underlying

mechanisms.

Methods: Male Wistar rats were randomly divided into

three groups: the normal control group, BDL group, and

α-KG treatment group (8 rats per group). BDL rats

were established by surgical ligation of the bile duct,

while the α-KG treatment group received daily oral

administration of 0.5 g/kg α-KG. After 4 weeks of

treatment, liver function, histopathology, and

apoptosis were assessed. Furthermore, bile leakage,

TGF-β1, and the Smad2/3 signaling pathway were also

investigated.

Results: Treatment with α-KG resulted in a

significant reduction in ALT, AST, and ALP levels

compared to the BDL group. α-KG treatment also

attenuated the liver histopathological changes and

decreased the number of apoptotic cells. Additionally,

α-KG inhibited bile leakage and downregulated the

TGF-β1 signaling pathway in the liver tissue, while

activating Smad2/3 expression.