The effect and significance of exogenous IGFBPrP1 on liver and kidney tissue in mice
-
摘要: 目的胶囊渗透压泵植入野生型小鼠皮下并持续恒量释放重组鼠胰岛素样生长因子结合蛋白相关蛋白1(rmIGFBPrP1),观察小鼠肝肾纤维化相关指标的表达,探讨rmIGFBPrP1对小鼠肝肾组织的影响及其可能的意义。方法将清洁级雄性C57BL/6野生型小鼠随机分为正常对照组、假手术组、模型组。采用胶囊渗透泵控释rmIGFBPrP1制备肝纤维化模型。HE染色、天狼猩红染色观察各组小鼠肝肾病理改变及胶原纤维沉积状况。免疫组织化学染色检测肝肾组织中IGFBPrP1、Smad3、p-Smad2/3、Ⅲ型胶原(CollagenⅢ)的表达和分布。原位缺口末端标记技术(TUNEL)检测肝细胞凋亡。结果与对照组和假手术组相比,模型组肝组织中胶原纤维含量增多,IGFBPrP1、Smad3、p-Smad2/3、CollagenⅢ表达增强(P<0.01)。模型组肾组织中仅IG-FBPrP1表达较对照组和假手术组有所增加,胶原纤维和其他指标表达未见差异(P>0.05)。TUNEL结果显示模型组肝细胞凋亡率增高,与正常组和假手术组相比,差异有统计学意义(P<0.01)。结论外源性IGFBPrP1可促进...
-
关键词:
- 胰岛素样生长因子结合蛋白相关蛋白1 /
- 肝硬化 /
- 细胞凋亡
Abstract: Objective To investigate the effect of exogenous recombinant mouse insulin-like growth factor binding protein related protein 1 (rmIGFBPrP1) on both liver and kidney tissue in mouse, and explore the mechanism of rmIGFBPrP1 on fibrosis.Methods A total of 26 clean male wild-type C57BL/6 mice were randomly divided into normal control group, sham-operated group and model group.The rmIGFBPrP1 which was released by capsule osmotic pump was used to make the model.HE staining and Sirius red staining were observed to investigate the pathological changes and deposition of collagen fibers in liver and kidney of mice.The expression and distribution of IGFBPrP1, Smad3, p-Smad2/3, III collagen (Collagen III) of liver and kidney tissues were detected by immunohistochemistry.Hepatocyte apoptosis was detected by DUTP nick end labeling (TUNEL) .Results Comparing with the control group and sham-operated group, the content of collagen fiber and the expression of IGFBPrP1, Smad3, p-Smad2/3, Collagen III increased (P<0.01) in the liver of model group, While only the expression of IGFBPrP1 in the kidney of model group increased than that in the control group and sham-operated group (P<0.01) , there is no difference of collagen fibers content and other indicators expression in these three groups (P>0.05) .TUNEL showed the increase in ratio of apoptotic liver cells in model group than that in normal group and sham-operated group (P<0.01) .Conclusion Exogenous IGFBPrP1 can promote hepatocyte apoptosis and liver fibrosis, while have little effect on the mice kidney.IGFBPrP1 may selectively induce organs and organization fibrosis in mice.-
Key words:
- insulin-like growth facter binding protein 1 /
- liver cirrhosis /
- apoptosis
-
[1]Lopez-Bermejo A, Khosravi J, Corless CL, et al.Generation ofanti-insulin-like growth factor-binding protein-related protein1 (IGFBPrP1/MAC25) monoclonal antibodies and immunoassay:quantification of IGFBPrP1 in human serum and distribution in hu-man fluids and tissues[J].J Clin Endocrinol Metab, 2003, 88 (7) :3401-3408. [2]Ma Y, Lu B, Ruan W, et al.Tumor suppressor gene insulin-likegrowth factor binding protein-related protein 1 (IGFBP-rP1) in-duces senescence-like growth arrest in colorectal cancer cells[J].Exp mol pathol, 2008, 85 (2) :141-145. [3]Pen A, Moreno MJ, Durocher Y, et al.Glioblastoma-secreted fac-tors induce IGFBP7 and angiogenesis by modulating Smad-2-de-pendent TGF-beta signaling[J].Oncogene, 2008, 20 (27) :6834-6844. [4]Liu LX, Huang S, Zhang QQ, et al.Insulin-like growth factorbinding protein-7 induces activation and transdifferentiation of he-patic stellate cells in vitro[J].World J Gastroenterology, 2009, 15 (26) :3246-3253. [5]Liu LX, Zhang HY, Zhang QQ.et al.Effects of insulin-likegrowth factor bingding protein 1 in mice with hepatic fibrosis inducedby thioacetamide[J].Chin Med J (Engl) , 2010, 123 (18) :2521-2526. [6] 曹平, 刘立新, 郭晓红, 等.Smad3沉默对IGFBPrP1诱导肝星状细胞分泌细胞外基质作用的影响[J].中华肝胆外科杂志, 2011, 2 (17) :142-146. [7]蔡卫民.肝脏炎症→纤维化→癌轴线分子生物学研究的某些进展[J].中华肝脏病杂志, 2009, 17 (10) :799-800 [8]辛绍杰, 赵景民, 王林杰, 等.病毒性肝炎肝细胞凋亡及与肝纤维化的关系[J].中华实验和临床病毒学杂志, 2000, 1 (14) :32-34. [9]Nousbeck J, Sarig O.Insulin-like growth factor-binding protein 7regulates keratinocyte proliferation, differentiation and apoptosis[J].J Invest Dermatol, 2010, 130 (2) :378-387. [10]Wajapeyee N, Serra RW.Oncogenic BRAF induces senescence andapoptosis through pathways mediated by the secreted protein IGFBP7[J].Cell, 2008, 132 (3) :363-374. [11]Chen RY, Chen HX.Intratumoral injection of pEGFC1-IGFBP7inhibits malignant melanoma growth in C57BL/6J mice by inducingapoptosis and down-regulating VEGF expression[J].Oncol Rep, 2010, 23 (4) :981-988.
本文二维码
计量
- 文章访问数: 3767
- HTML全文浏览量: 15
- PDF下载量: 6
- 被引次数: 0