Peng Jian, Yue Chunyan, Qiu Kai, Chen Jie, Aller Maria-Angeles, Ko Kwang Suk, Yang Heping
National Hepatobiliary and Enteric Surgery Research Center, Xiangya Hospital of Central South University, 87 Xiangya Road, Changsha, Hunan 410008, China.
Surgery Department, School of Medicine, Complutense University, Madrid, Spain.
ISRN Hepatol. 2013 Nov 17;2013:601071. doi: 10.1155/2013/601071. eCollection 2013.
Background. Cholestatic liver injury is a leading cause of chronic liver diseases involved with oxidative stress changes and inflammation; thus, antioxidant and anti-inflammation compound-rich guava may play a pivotal role in protecting against the cholestatic liver damages. Our aims for this study are to determine whether guava pulp (GP) has protective effects on cholestatic liver injury-induced mouse model and on interleukin-6 (IL-6) mediated proliferation of QBC939 cholangiocarcinoma cell line. Methods. Mice were induced to cholestatic liver damage by left and median bile duct ligation (LMBDL) surgery and then treated with GP. Plasma and liver samples were collected for biochemical and pathological assays. 5-Bromo-2'-deoxyuridine (BrdU) assay and Western blots were used to detect proliferation and gene expression in QBC939 cells, respectively. Results. Compared with LMBDL only group, in GP-treated mice, the levels of alanine aminotransferase (ALT) and bilirubin decreased, biliary epithelial cell proliferation and liver fibrogenesis were suppressed, Src/MEK/ERK1/2/c-Myc pathway and expressions of transforming growth factor β1(TGF-β1), tissue inhibitor of metalloproteinases TIMP), and procollagen 1α1(COL1α1) were downregulated significantly. Moreover, the GP extract reduced IL-6-enhanced QBC939 cell proliferation, p-ERK, and c-Myc expression as well. Conclusions. GP may provide a new perspective for the treatment of cholestatic liver injury.
背景。胆汁淤积性肝损伤是慢性肝病的主要病因,与氧化应激变化和炎症有关;因此,富含抗氧化剂和抗炎化合物的番石榴可能在预防胆汁淤积性肝损伤中发挥关键作用。本研究的目的是确定番石榴果肉(GP)对胆汁淤积性肝损伤诱导的小鼠模型以及白细胞介素-6(IL-6)介导的QBC939胆管癌细胞系增殖是否具有保护作用。方法。通过左和中胆管结扎(LMBDL)手术诱导小鼠发生胆汁淤积性肝损伤,然后用GP进行治疗。收集血浆和肝脏样本进行生化和病理分析。分别使用5-溴-2'-脱氧尿苷(BrdU)测定法和蛋白质免疫印迹法检测QBC939细胞中的增殖和基因表达。结果。与仅接受LMBDL手术的组相比,在接受GP治疗的小鼠中,丙氨酸转氨酶(ALT)和胆红素水平降低,胆管上皮细胞增殖和肝纤维化受到抑制,Src/MEK/ERK1/2/c-Myc信号通路以及转化生长因子β1(TGF-β1)、金属蛋白酶组织抑制剂(TIMP)和前胶原1α1(COL1α1)的表达均显著下调。此外,GP提取物还降低了IL-6增强的QBC939细胞增殖、p-ERK和c-Myc表达。结论。GP可能为胆汁淤积性肝损伤的治疗提供新的视角。