Xia Wanrong, Yao Hongji, Mu Tongxin, Liu Hui, Chen Jianhua, Feng Shi, Wen Shilei
Key Laboratory of Tropical Translational Medicine of Ministry of Education and Key Laboratory of Brain Science Research Transformation in Tropical Environment of Hainan Province, School of Basic Medicine and Life Sciences, Hainan Medical University, Haikou, Hainan 571199, P.R. China.
Department of Human Anatomy, College of Basic Medicine and Life Sciences, Hainan Medical University, Haikou, Hainan 571199, P.R. China.
Exp Ther Med. 2025 Jul 3;30(3):167. doi: 10.3892/etm.2025.12917. eCollection 2025 Sep.
Common bile duct ligation (BDL) in rats is a widely used animal model for the study of cholestatic liver injury; however, it has a high mortality rate and leads to rapid disease progression. To address these limitations, the present study developed a simplified partial BDL (p-BDL) procedure by inserting a 26G disposable venous indwelling needle during ligation of the common bile duct, and subsequently removing the needle to create a narrow passage through the ligature points. The rats were euthanized 1 or 2 months after the procedure for histological, immunohistochemical and gelatin zymography analyses of the liver. Notably, no animals died during the experimental period, demonstrating the low mortality rate of the model. When assessed 1 month post-p-BDL, the rats exhibited mild liver fibrosis, while at 2 months, severe liver fibrosis was observed. Corresponding changes in liver function indices were also noted. Specifically, markers of liver fibrosis, including collagen I, collagen III and α-smooth muscle actin, as well as matrix metalloproteinase (MMP)-2 and MMP-9, which contribute to extracellular matrix degradation, were significantly upregulated following p-BDL. These findings are similar to those observed following BDL, and indicate that the p-BDL model was successfully established. This model mitigates the drawbacks of traditional BDL and mimics chronic cholestatic cirrhosis, as observed clinically.
大鼠胆总管结扎（BDL）是一种广泛用于研究胆汁淤积性肝损伤的动物模型；然而，该模型死亡率高且疾病进展迅速。为解决这些局限性，本研究开发了一种简化的部分BDL（p-BDL）方法，即在结扎胆总管时插入一根26G一次性静脉留置针，随后拔出该针以在结扎点处形成一条狭窄通道。术后1或2个月对大鼠实施安乐死，以对肝脏进行组织学、免疫组织化学和明胶酶谱分析。值得注意的是，实验期间无动物死亡，表明该模型死亡率低。在p-BDL术后1个月进行评估时，大鼠表现出轻度肝纤维化，而在2个月时观察到严重肝纤维化。肝功能指标也出现了相应变化。具体而言，肝纤维化标志物，包括I型胶原、III型胶原和α-平滑肌肌动蛋白，以及参与细胞外基质降解的基质金属蛋白酶（MMP）-2和MMP-9，在p-BDL后均显著上调。这些发现与BDL后观察到的结果相似，表明成功建立了p-BDL模型。该模型减轻了传统BDL的缺点，并模拟了临床上观察到的慢性胆汁淤积性肝硬化。
