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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可促进小鼠肝细胞凋亡和肝纤维化的形成,而对小鼠肾组织影响甚微。IGFBPrP1致小鼠脏器组织纤维化可能具有选择性。
OBJECTIVE To study the effect of rmIGFBPrP1 on liver and kidney in mice and to investigate the effect of rmIGFBPrP1 on the expression of rmIGFBP-1, The impact of organization and its possible implications. Methods Clean-grade male C57BL / 6 wild-type mice were randomly divided into normal control group, sham operation group and model group. The hepatic fibrosis model was prepared by controlled release of rmIGFBPrP1 by capsule osmotic pump. Hematoxylin and eosin staining and Sirius red staining were used to observe the pathological changes of liver and kidney and collagen deposition in mice. Immunohistochemical staining was used to detect the expression and distribution of IGFBPrP1, Smad3, p-Smad2 / 3 and CollagenⅢ in liver and kidney tissues. In situ nick end labeling (TUNEL) was used to detect hepatocyte apoptosis. Results Compared with the control group and the sham operation group, the collagen fibers in the model group increased and the expressions of IGFBPrP1, Smad3, p-Smad2 / 3 and Collagen Ⅲ increased (P <0.01). The expression of IG-FBPrP1 in model group was higher than that in control group and sham-operated group, but there was no difference between collagen fibers and other indexes (P> 0.05). The results of TUNEL showed that the rate of hepatocyte apoptosis in model group was higher than that in normal group and sham operation group (P <0.01). Conclusion Exogenous IGFBPrP1 can promote hepatocyte apoptosis and hepatic fibrosis in mice, but has little effect on mouse kidney tissue. IGFBPrP1 Mice Organ Tissue Fibrosis May Be Selective.