Department of Surgery, School of Clinical Medicine, Queen Mary Hospital, The University of Hong Kong, 102 Pokfulam Road, Hong Kong SAR, China.
Dr. Li Dak-Sum Research Centre, The University of Hong Kong, Hong Kong SAR, China.
Pediatr Surg Int. 2024 Aug 5;40(1):214. doi: 10.1007/s00383-024-05798-7.
We performed animal and organoid study to evaluate the anti-fibrotic effect of steroid on biliary atresia (BA) and the underlying patho-mechanism.
BA animal models were created by inoculation of mice on post-natal day 1 with rhesus rotavirus (RRV). They received either 20 µl phosphate-buffered saline (PBS) or steroid from day 21 to day 34. On day 34, their serum samples were collected for hormonal markers. Necrosis, fibrosis and CK 19 expression in the liver were evaluated. Liver organoids were developed and their morphology as well as bulk RNA sequencing data were analyzed.
Twenty-four mice developed BA features after RRV injection and were equally divided into steroid and PBS groups. On day 34, the weight gain of steroid group increased significantly than PBS group (p < 0.0001). All mice in the PBS group developed liver fibrosis but only one mouse in the steroid group did. Serum bilirubin and liver parenchymal enzymes were significantly lower in steroid group. The morphology of liver organoids were different between the two groups. A total of 6359 differentially expressed genes were found between steroid group and PBS group.
Based on our findings obtained from RRV-induced BA animal and organoid models, steroid has the potential to mitigate liver fibrosis in BA.
我们进行了动物和类器官研究，以评估类固醇对胆道闭锁（BA）的抗纤维化作用及其潜在的病理机制。
通过在出生后第 1 天给小鼠接种恒河猴轮状病毒（RRV）来建立 BA 动物模型。从第 21 天到第 34 天，它们分别接受 20µl 磷酸盐缓冲盐水（PBS）或类固醇治疗。在第 34 天，采集它们的血清样本用于激素标志物检测。评估肝脏的坏死、纤维化和 CK19 表达。开发了肝类器官，并分析了它们的形态和大量 RNA 测序数据。
24 只小鼠在 RRV 注射后出现 BA 特征，并被平均分为类固醇组和 PBS 组。在第 34 天，类固醇组的体重增加明显高于 PBS 组（p<0.0001）。PBS 组的所有小鼠均发生肝纤维化，但类固醇组只有 1 只小鼠发生。类固醇组的血清胆红素和肝实质酶明显较低。两组肝类器官的形态不同。在类固醇组和 PBS 组之间发现了 6359 个差异表达基因。
基于我们从 RRV 诱导的 BA 动物和类器官模型中获得的发现，类固醇有可能减轻 BA 中的肝纤维化。
