奥曲肽抗肝纤维化的实验研究  

Therapeutic effects of octreotide on hepatofibrosis-induced with carbon tetrachloride in rats

作　　者：王志荣[1] 李定国[2] 陈锡美[1] 黄新[2] 魏红山[2] 汪余勤[2] 徐芹芳[2] 陆汉明[2] 

机构地区：[1]同济大学附属同济医院消化内科,上海200065 [2]上海第二医科大学附属新华医院消化内科

出　　处：《中华肝脏病杂志》2003年第7期408-411,共4页Chinese Journal of Hepatology

摘　　要：目的 观察奥曲肽(Oct)对大鼠实验性肝纤维化的治疗效果,并探讨其作用机制。方法 用四氯化碳诱导大鼠肝纤维化模型,将实验动物随机分为正常对照组、治疗前模型组、治疗后模型组和Oct治疗组。Oct治疗组给予Oct(50ng/100g)皮下注射,每日2次,连续用药30d,分别用放射免疫法检测血清层黏连蛋白(LN)、Ⅲ型前胶原(PC Ⅲ)及透明质酸(HA)。VG染色法组织切片观察组织病理变化,免疫组织化学法检测肝组织平滑肌肌动蛋白(α-SMA)和转化生长因子β_1(TGFβ_1)表达及逆转录聚合酶链反应法检测Ⅰ型和Ⅲ型前胶原mRNA表达。结果 治疗前和治疗后模型组大鼠血清HA(ng/L)为121.8±9.5和110.3±13.4,正常对照组为33.1±3.7、LN(μg/L)为85.7±12.1和78.2±7.9,正常对照组为37.1±6.3、PC Ⅲ(ng/L)为35.9±3.5和33.7±2.6,正常对照组为15.6±2.8。Oct组大鼠血清HA为55.8±7.2、LN为43.1±3.4、PC Ⅲ为27.8±3.4,与模型组大鼠比较,差异有显著性,t=2.76～11.07,P<0.05。Oct能显著降低纤维化大鼠肝组织纤维化积分,下调α—SMA和TGFβ_1蛋白质及I型和III前胶原mRNA表达水平。结论 Oct抑制肝星状细胞激活和转化、下调TGFβ_1蛋白质及I型和III型前胶mRNA表达而发挥抗肝纤维化作用。Objectives To investigate the therapeutic effects and mechanism of octreotide on experimental hepatic fibrosis in rats. Methods Hepatofibrotic rats models were established with carbon tetrachloride. All the experimental rats were divided into four groups: normal control group, pre-and post-treatment model group, and octreotide-treated group in which the rats were injected subcutaneously with octreotide at the dose of 50 ng/100 g, twice daily, for thirty days. Serum levels of hyaluronic acid (HA), laminin (LN) and pro-collagen type III peptide(PCIII) were detected by radioimmunoassay. Hepatic fibrosis scoring grade was assessed through Van-Gieson staining and observed under light microscope. Protein expression levels of a-smooth muscle actin (a-SMA) and transforming growth factor betal (TGF β1 were determined with immunohistochemical staining method. Messenger RNA (mRNA) levels of collagen type I and PCIII were detected by reverse transcription polymerase chain reaction. Results Serum levels of HA (ng/L), LN (μg/L) and PCIII (ng/L) in pre- and post-treatment model groups were higher than those in normal control group(121.8 ± 9.5 and 110.3 ± 13.4 vs 33.1 ± 3.7, 85.7 ± 12.1 and 78.2 ± 7.9 vs 37.1 ± 6.3, 35.9 ± 3.5 and 33.7 ± 2.6 vs 15.6 ± 2.8, respectively, t > 9.41, P < 0.05), and there was no significant difference between the two model groups. Concentrations of HA (55.8 ng/L ± 7.2 ng/L), LN (43.1 #g/L ± 3.4μg/L) and PCIII (27.8 ng/L ± 3.4 ng/L) decreased significantly in octreotide-treated group, compared with those in model groups (t > 2.76, P < 0.05). With histological analysis, fibrotic scoring grade in octreotide-treated group was obviously ameliorated, compared with that in model groups ( x2≥ 3.97, P< 0.05). Imaging analysis revealed that a -SMA and TGF β1 immunohistological staining areas were markedly shrinked in octreotide-treated group (t > 2.47, P < 0.05). In two model groups, PCIII and type I mRNA levels significantly up-regulated as compared with those in normal group (t ≥ 9.27, P

关 键 词：奥曲肽 肝纤维化 OCT 治疗 肝组织 免疫组织化学 

分 类 号：R575[医药卫生—消化系统] R969.4[医药卫生—内科学]