Ma Hucheng, Shi Xiaolei, Yuan Xianwen, Ding Yitao
Department of Hepatobiliary Surgery, Affiliated DrumTower Hospital of Nanjing University Medical School, Jiangsu Province, China.
Ann Hepatol. 2016 Mar-Apr;15(2):260-70. doi: 10.5604/16652681.1193723.
Uncontrolled hapatic inflammatory response is regarded as the primary pathological mechanism of acute liver failure and impairs the regeneration of hepatocytes and stem cell grafts. Interleukin-1 plays a key role for activating immune and inflammatory response. Recently, siRNA has made quite a few progresses in treating inflammatory response.
To assess the effect of IL-1? siRNA adenovirus on MSC and the therapeutic effect of MSC combined with IL-1? siRNA adenovirus in ALF.
We implanted MSC or/and IL-1? siRNA adenovirus via the tail vein, using CCl4-induced ALF in a mice model. Mice were sacrificed at different time points. Blood samples and liver tissues were collected. Hepatic injury, liver regeneration, cytokines (CXCL1, IL-1?, IL-10, IL-6, VEGF and HGF), animal survival and vital MSC were assessed after cell transplantation.
MSC combined with IL-1? siRNA reduced the inflammatory levels and prevented liver failure. These animals administrated with MSC and IL-1? siRNA also exhibited improved liver regeneration and increased survival rates. Immunohistochemistry and fluorescence microscopy revealed the number of vital MSC in ALF + MSC + IL-1? siRNA group were significantly more than that in ALF + MSC group.
IL-1? siRNA adenovirus could enhance MSC ability of tissue regeneration through increasing its survival rate. Accordingly, combination of IL-1? siRNA adenovirus and MSC had a synergistic effect on acute liver failure.
失控的肝脏炎症反应被认为是急性肝衰竭的主要病理机制，会损害肝细胞和干细胞移植的再生。白细胞介素-1在激活免疫和炎症反应中起关键作用。最近，小干扰RNA（siRNA）在治疗炎症反应方面取得了不少进展。
评估白细胞介素-1α siRNA腺病毒对间充质干细胞（MSC）的作用以及MSC联合白细胞介素-1α siRNA腺病毒在急性肝衰竭（ALF）中的治疗效果。
我们通过尾静脉注射MSC或/和白细胞介素-1α siRNA腺病毒，采用四氯化碳诱导的小鼠急性肝衰竭模型。在不同时间点处死小鼠。采集血样和肝组织。在细胞移植后评估肝损伤、肝再生、细胞因子（CXCL1、白细胞介素-1α、白细胞介素-10、白细胞介素-6、血管内皮生长因子和肝细胞生长因子）、动物存活率和存活的MSC。
MSC联合白细胞介素-1α siRNA降低了炎症水平并预防了肝衰竭。给予MSC和白细胞介素-1α siRNA的这些动物还表现出肝再生改善和存活率提高。免疫组织化学和荧光显微镜检查显示，急性肝衰竭+MSC+白细胞介素-1α siRNA组中存活的MSC数量明显多于急性肝衰竭+MSC组。
白细胞介素-1α siRNA腺病毒可通过提高其存活率增强MSC的组织再生能力。因此，白细胞介素-1α siRNA腺病毒与MSC联合应用对急性肝衰竭具有协同作用。
