论文部分内容阅读
目的探讨携带人白细胞介素10(hIL-10)基因的腺病毒的抗炎和抗纤维化作用。方法实验大鼠分为实验组(60只)和对照组(15只)。实验组均分为3组,腹腔分别注射40%四氯化碳(CCl4)石蜡油溶液(CCl4组)、CCl4+EGFP(Ad-EGFP组)和CCl4+hIL-10(Ad-hIL-10组)。依据用药时间又分为治疗1周组、2周组、3周组和4周组。检测肝功能和肝纤维化4项指标,观察肝脏组织病理变化。采用免疫荧光双标记法和激光扫描共聚焦显微镜观察活化肝星状细胞(HSC)中hIL-10表达。结果治疗1周组中,Ad-hIL-10组的TBil、ALT、AST降低和ALB增高比Ad-EGFP组和CCl4组明显(P<0.05)。Ad-hIL-10组的ALT、AST降低和TP、ALB升高程度:4周组>3周组>2周组>1周组(P<0.05)。治疗4周组中,Ad-hIL-10组肝纤维化4项指标均低于CCl4组(P<0.05)。Ad-hIL-10组肝脏纤维化程度明显较CCl4组轻。肝脏HSC中的hIL-10表达与α-平滑肌肌动蛋白(α-SMA)表达呈负相关(r=-0.812,P<0.05)。结论携带hIL-10基因的腺病毒具有抗炎和抗纤维化的作用。其抗纤维化的机制可能与其抑制HSC的活化有关。
Objective To investigate the anti-inflammatory and anti-fibrotic effect of adenovirus carrying human interleukin 10 (hIL-10) gene. Methods Experimental rats were divided into experimental group (60 rats) and control group (15 rats). The experimental groups were divided into 3 groups: CCl4 group, CCl4 + EGFP group, CCl4 + hIL-10 group (Ad-hIL-10 group) were injected intraperitoneally with 40% CCl4 paraffin oil solution ). According to medication time is divided into treatment 1 week group, 2 weeks group, 3 weeks group and 4 weeks group. Liver function and liver fibrosis were detected 4 indicators, pathological changes observed in liver tissue. The expression of hIL-10 in activated hepatic stellate cells (HSC) was observed by immunofluorescence double labeling and laser scanning confocal microscopy. Results In the 1-week treatment group, the decrease of TBil, ALT, AST and the increase of ALB in Ad-hIL-10 group were more obvious than those in Ad-EGFP group and CCl4 group (P <0.05). The levels of ALT and AST and the levels of ALB and ALB in Ad-hIL-10 group were higher than that in Ad-hIL-10 group: 4 weeks group> 3 weeks group> 2 weeks group> 1 week group (P <0.05). Four weeks treatment group, four indicators of liver fibrosis in Ad-hIL-10 group were lower than CCl4 group (P <0.05). The degree of hepatic fibrosis in Ad-hIL-10 group was significantly lighter than that in CCl4 group. The expression of hIL-10 in hepatic HSC was negatively correlated with the expression of α-smooth muscle actin (α-SMA) (r = -0.812, P <0.05). Conclusion Adenovirus carrying hIL-10 gene has anti-inflammatory and anti-fibrotic effects. Its anti-fibrosis mechanism may be related to its inhibition of HSC activation.