Background Polycystic liver disease (PLD) is hereditary liver disease in which the number of cysts increases over time, causing various abdominal symptoms and a poor quality of life. Although effective treatment for PLD has not been established, we recently reported that long-term exercise ameliorated liver cyst formation and fibrosis with activation of AMP-activated protein kinase (AMPK) in polycystic kidney (PCK) rats, a PLD model. Therefore, the aim of this study was to investigate whether metformin, an indirect AMPK activator, was effective in PCK rats. Methods PCK rats were randomly divided into a control (Con) group and a metformin group (Met group). The Met group was treated orally with metformin in drinking water. After 12 weeks, liver function, histology and signaling cascades of PLD were examined in the groups. Results Metformin did not affect body weight or liver weight, but it reduced liver cyst formation, fibrosis and Ki-67-positive cells around the cyst. Metformin increased the phosphorylation of AMPK and decreased the phosphorylation of mammalian target of rapamycin and extracellular signal-regulated kinase and the expression of cystic fibrosis transmembrane conductance regulator, aquaporin I, transforming growth factor-β and type 1 collagen in the liver. Conclusions Metformin slows the development of cyst formation and fibrosis with activation of AMPK and inhibition of signaling cascades responsible for cellular proliferation and fibrosis in the liver of PCK rats.

中文翻译：

---

在多囊性肝病的实验模型中，二甲双胍减缓了肝囊肿的形成和纤维化。

背景技术多囊性肝病（PLD）是一种遗传性肝病，其中囊肿的数量随时间增加，导致各种腹部症状和不良的生活质量。尽管尚未建立有效的PLD治疗方法，但我们最近报道，长期运动可通过激活PLD模型多囊肾（PCK）大鼠中的AMP激活的蛋白激酶（AMPK）来改善肝囊肿的形成和纤维化。因此，本研究的目的是研究二甲双胍（一种间接的AMPK激活剂）是否对PCK大鼠有效。方法将PCK大鼠随机分为对照组（Con）组和二甲双胍组（Met组）。Met组在饮用水中口服二甲双胍治疗。12周后，检查各组的肝功能，PLD的组织学和信号传导级联。结果二甲双胍不影响体重或肝脏重量，但减少了肝囊肿的形成，纤维化和囊肿周围Ki-67阳性细胞。二甲双胍增加了AMPK的磷酸化，并降低了哺乳动物雷帕霉素靶标和细胞外信号调节激酶的磷酸化，并降低了肝脏中囊性纤维化跨膜电导调节剂，水通道蛋白I，转化生长因子-β和1型胶原的表达。结论二甲双胍可通过激活AMPK并抑制PCK大鼠肝脏中细胞增殖和纤维化的信号级联反应而减缓囊肿形成和纤维化的发展。二甲双胍增加了AMPK的磷酸化，并降低了哺乳动物雷帕霉素靶标和细胞外信号调节激酶的磷酸化，并降低了肝脏中囊性纤维化跨膜电导调节剂，水通道蛋白I，转化生长因子-β和1型胶原的表达。结论二甲双胍可通过激活AMPK并抑制PCK大鼠肝脏中细胞增殖和纤维化的信号级联反应而减缓囊肿形成和纤维化的发展。二甲双胍增加了AMPK的磷酸化，并降低了哺乳动物雷帕霉素靶标和细胞外信号调节激酶的磷酸化，并降低了肝脏中囊性纤维化跨膜电导调节剂，水通道蛋白I，转化生长因子-β和1型胶原的表达。结论二甲双胍可通过激活AMPK并抑制PCK大鼠肝脏中细胞增殖和纤维化的信号级联反应而减缓囊肿形成和纤维化的发展。