重组血管内皮生长因子165对大鼠肝纤维化的影响  

Portal vein infusion of recombinant vascular endothelial growth factor 165 mitigates liver fibrosis in cirrhotic rats

作　　者：于良立[1] 赵金满[1] 蒋伟伟[1] 

机构地区：[1]中国医科大学附属第一医院消化内科,辽宁省沈阳市110001

出　　处：《世界华人消化杂志》2011年第21期2214-2219,共6页World Chinese Journal of Digestology

摘　　要：目的:探讨经门静脉导入重组血管内皮生长因子165对大鼠肝纤维化的影响.方法:♂SD大鼠50只,体质量180-220g,完全随机分成正常组10只、诱导模型组40只.采用硫代乙酰胺诱导模型方法,10wk后成模25只,随机分为模型实验组15只和模型对照组10只,实验组经门静脉插管并植入Alzet微渗泵灌注血管内皮生长因子入门静脉,持续作用2wk.正常组和模型对照组行开腹后关腹对照处理.2wk后处死大鼠,HE染色观察肝脏病理组织学改变;放射免疫法检测血清HA、LN含量;免疫组织化学法检测肝组织内Ⅰ、Ⅳ型胶原含量.结果:模型对照组肝细胞变性坏死、弥漫纤维结缔组织增生,有假小叶形成.而模型实验组变性坏死程度减轻,纤维结缔组织增生范围缩小,肝纤维化分级较模型对照组有明显的改善,差异具有统计学意义(P<0.01).与正常组比较,模型对照组血清HA、LN浓度急剧增高,差异具有统计学意义(741.60μg/L±72.83μg/Lvs46.11μg/L±12.10μg/L;92.80μg/L±8.41μg/Lvs27.74μg/L±3.29μg/L;均P<0.01);模型实验组血清HA、LN浓度与模型对照组比较显著下降,差异具有统计学意义(412.63μg/L±85.18μg/Lvs741.60μg/L±72.83μg/L;58.87μg/L±5.46μg/Lvs92.80μg/L±8.41μg/L;均P<0.01);Ⅰ、Ⅳ型胶原免疫组织化学定量分析结果显示,模型实验组明显低于模型对照组,差异具有统计学意义(6.84±0.96,8.25±0.82vs18.32±1.86,20.84±2.42,均P<0.01).结论:经门静脉灌注重组血管内皮生长因子165具有减缓大鼠肝纤维化的作用.AIM： To evaluate the effect of portal vein infu- sion of recombinant vascular endothelial growth factor （VEGF） 165 on liver fibrosis in rats with cirrhosis. METHODS： Fifty male SD rats were randomly divided into normal group （n = 10） and model group （n = 40）. The model group was used to in- duce cirrhosis using the thioacetamide approach. After 10 wk, 25 cirrhotic rats were randomly divided into experimental group （n = 15） and model control group （n = 10）. The experimen- tal group was intubated for implantation of an Alzet osmotic pump, which was used to infuse recombinant VEGF165 via the portal vein for 2 wk. The normal group and model control groupunderwent sham operation. All rats were killed after 2 wk, and HE staining was used to observe the pathological changes in liver tissue. Serum hyaluronic acid and laminin were measured us- ing radioimmunoassay method. Immunohisto- chemistry was used to detect the expression of type I and type IV collagen in the liver. RESULTS： Degeneration and necrosis of liver cells, diffuse proliferation of fibrous connective tissue and formation of pseudo lobules occurred in the model control group. In the experimental group, degeneration and necrosis of liver cells were milder and the rate of liver fibrosis was improved significantly compared to the model control group （P 〈 0.01）. Compared to the nor- mal group, serum hyaluronic acid and laminin concentrations increased significantly in the model control group （P 〈 0.01）. However, serum concentrations of hyaluronic acid and laminin was significantly lower in the experimental group than in the model control group （412.63 μg/L ±85.18 μg/L vs 741.60 μg/L ±72.83 μg/L; 58.87 μg/L ± 5.46μg/L vs 92.80 μg/L ± 8.41 μg/L; both P 〈 0.01）. The expression levels of type I and type IV collagen in the liver was signifi- cantly lower in the experimental group than in the model control group （6.84 ±0.96, 8.25± 0.82 vs 18.38± 1.86, 20.86± 2.48, all P 〈 0.01）.CONCLUSION： Portal vein

关 键 词：血管内皮生长因子 肝纤维化 血管生成 

分 类 号：R575.2[医药卫生—消化系统]