Huang Yue-Hong, Chen Yun-Xin, Zhang Li-Juan, Chen Zhi-Xin, Wang Xiao-Zhong
Department of Gastroenterology, Fujian Medical University Union Hospital, Fuzhou, Fujian 350001, P.R. China.
Int J Mol Med. 2014 Sep;34(3):677-86. doi: 10.3892/ijmm.2014.1831. Epub 2014 Jul 2.
Liver fibrosis is the common pathological outcome for the majority of chronic liver diseases. Interleukin-10 (IL-10) is a cytokine that downregulates proinflammatory responses and has a modulatory effect on liver fibrogenesis. However, little is known regarding the effect of rat interleukin‑10 (rIL‑10) gene by hydrodynamics-based transfection (HBT) on liver fibrosis in rats. The aim of this study was to investigate the effect of the rIL-10 gene by HBT on the progression of liver fibrosis induced by porcine serum (PS) in rats and explore its possible mechanism. Plasmid‑expressing rIL-10 was transferred into rats by HBT and immunohistochemistry and RT-PCR were used to detect the major organ expressing rIL-10. Liver fibrosis was induced in rats by intraperitoneal administration of PS for 8 weeks. Plasmid pcDNA3-rIL-10 solution was administered weekly by HBT starting at the 5th week. Liver function and hepatic histology were examined. The possible molecular mechanisms of rIL-10 gene therapy were assessed in liver tissue and hepatic stellate cells (HSCs) co-cultured with BRL cells (a hepatocyte line) in vitro. The results showed rIL-10 expression occurred mainly in the liver following rIL-10 gene transfer by HBT. Maintaining a stable expression of rIL-10 in serum was assessed by repeated administration. The rIL-10 gene treatment attenuated liver inflammation and fibrosis in PS-induced fibrotic rats, reduced the deposition of collagen and the expression of α-smooth muscle actin (α-SMA) in fibrotic rats. The in vitro experiment showed that the expression of a-SMA and procollagen type I in HSCs co-cultured with the BRL‑transfected rIL-10 gene were significantly decreased. These findings indicate that rIL-10 gene therapy by HBT attenuates PS-induced liver fibrosis in rats and that its mechanism is associated with rIL-10 inhibiting the activation of HSCs and promoting the degeneration of collagen.
肝纤维化是大多数慢性肝病常见的病理转归。白细胞介素-10（IL-10）是一种下调促炎反应并对肝纤维化形成具有调节作用的细胞因子。然而，关于基于流体动力学转染（HBT）的大鼠白细胞介素-10（rIL-10）基因对大鼠肝纤维化的影响知之甚少。本研究旨在探讨通过HBT转染rIL-10基因对猪血清（PS）诱导的大鼠肝纤维化进程的影响，并探索其可能的机制。通过HBT将表达rIL-10的质粒转入大鼠体内，采用免疫组织化学和逆转录-聚合酶链反应（RT-PCR）检测表达rIL-10的主要器官。通过腹腔注射PS 8周诱导大鼠肝纤维化。从第5周开始每周通过HBT给予质粒pcDNA3-rIL-10溶液。检测肝功能和肝脏组织学。在体外与BRL细胞（一种肝细胞系）共培养的肝组织和肝星状细胞（HSCs）中评估rIL-10基因治疗的可能分子机制。结果显示，通过HBT进行rIL-10基因转移后，rIL-10主要在肝脏中表达。通过重复给药评估血清中rIL-10的稳定表达情况。rIL-10基因治疗减轻了PS诱导的纤维化大鼠的肝脏炎症和纤维化，减少了纤维化大鼠中胶原蛋白的沉积和α-平滑肌肌动蛋白（α-SMA）的表达。体外实验表明，与转染rIL-10基因的BRL细胞共培养的HSCs中，Ⅰ型α-SMA和前胶原的表达显著降低。这些研究结果表明，通过HBT进行rIL-10基因治疗可减轻PS诱导的大鼠肝纤维化，其机制与rIL-10抑制HSCs活化和促进胶原蛋白降解有关。
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