新生鼠肾积水病肾组织转化生长因子β1、单核细胞趋化蛋白-1、胰岛素样生长因子-1、内皮素-1蛋白水平表达变化的意义

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[摘要]目的 探討新生鼠肾积水病肾组织转化生长因子β1（TGF-β1）、单核细胞趋化蛋白-1（MCP-1）、胰岛素样生长因子-1（IGF-1）、内皮素-1（ET-1）蛋白水平表达变化的意义。方法 选取新生48 h内的Wistar鼠72只，随机分为6组，每组12只，随机选择1组作为对照组，其余5组均制作成输尿管左侧部分梗阻的动物模型。通过HE染色法观察病肾组织的病理结构变化并对病肾组织做出相应的病理学分级;通过免疫组化SP法检测新生鼠的肾脏组织中TGF-β1、MCP-1、IGF-1、ET-1的蛋白水平表达情况。结果 在梗阻解除后12周，模型组中TGF-β1的蛋白表达量与对照组比较，差异无统计学意义（P>0.05）;模型组的ET-1、MCP-l蛋白表达量（6.20±1.16，3.34±0.06）高于对照组（2.27±0.73，0.71±0.25），差异有统计学意义（P<0.05）;模型组的IGF-1蛋白表达量（18.12±1.08）低于对照组（28.38±4.82），差异有统计学意义（P<0.05）。模型组各病理学分级（Ⅰ、Ⅱ、Ⅲ、Ⅳ级）新生鼠的TGF-β1蛋白表达量比较，差异均有统计学意义（P<0.05）。模型组Ⅱ级新生鼠的ET-1、MCP-1蛋白表达量与Ⅰ级的比较，差异无统计学意义（P>0.05），Ⅲ、Ⅳ级的ET-1、MCP-1蛋白表达量高于Ⅱ级，差异有统计学意义（P<0.05）。模型组Ⅱ、Ⅲ、Ⅳ级新生鼠的IGF-1蛋白表达量低于Ⅰ级，模型组Ⅳ级新生鼠的IGF-1蛋白表达量低于Ⅲ级，差异均有统计学意义（P<0.05），模型组Ⅱ级新生鼠的IGF-1蛋白表达量与Ⅲ级比较，差异无统计学意义（P>0.05）。TGF-β1、MCP-l、ET-1、IGF-1的蛋白表达量在梗阻解除后的不同时间点比较：梗阻解除后6、8、12周，模型组中的TGF-β1、MCP-l、ET-1蛋白表达量均低于梗阻解除后2周，IGF-1蛋白表达量高于梗阻解除后2周，差异有统计学意义（P<0.05）。模型组中梗阻解除后2周的TGF-β1、MCP-l、ET-1、IGF-1蛋白表达量与梗阻解除后0周比较，差异无统计学意义（P>0.05）。模型组中梗阻解除后8周的TGF-β1、MCP-l、ET-1、IGF-1蛋白表达量与梗阻解除后6周比较，差异无统计学意义（P>0.05）。梗阻解除后12周，模型组中的TGF-β1、MCP-l、ET-1蛋白表达量均低于梗阻解除后8周，IGF-1蛋白表达量高于梗阻解除后8周，差异有统计学意义（P<0.05）。TGF-β1的蛋白表达量与病理学分级均成正相关关系（r=0.873，P<0.01）;ET-1、MCP-1的蛋白表达量与病理学分级均成正相关关系（r=0.579、0.637，P<0.05）;IGF-1的蛋白表达量与病理学分级无明显的相关性（P>0.05）。结论 病肾组织的组织病理学改变随梗阻解除时间延长而逐渐恢复。TGF-β1的蛋白水平表达随梗阻病理学分级的增加而增加，随梗阻解除的时间延长而逐渐下降。TGF-β1可作为新生鼠肾积水病肾的损害程度及恢复情况判定的可靠指标。

[关键词]新生鼠;肾积水;蛋白水平

[中图分类号] R693     [文献标识码] A     [文章编号] 1674-4721（2019）9（b）-0015-06

Significance of expression changes of transforming growth factor β1， monocyte chemoattractant protein-1， insulin-like growth factor-1， endothelin-1 proteins in renal tissues of neonatal rats with hydronephrosis

TIAN Wen-chao1   MA Hong2   LIU Xian-xian3   ZHENG Bu-feng1   FU Ting-liang1

1. Department of Pediatric Surgery， Affiliated Hospital of Binzhou Medical College， Shandong Province， Binzhou   256603， China; 2. Department of Pediatric Surgery， Affiliated Hospital of Zunyi Medical College， Guizhou Province， Zunyi   563003， China; 3. Department of Infectious Diseases， Affiliated Hospital of Binzhou Medical College， Shandong Province，  Binzhou   256603， China

[Abstract] Objective To investigate the significance of changes in the expression of transforming growth factor β1 （TGF-β1）， monocyte chemoattractant protein-1 （MCP-1）， insulin-like growth factor-1 （IGF-1） and endothelin-1 （ET-1） proteins in renal tissue of neonatal rat hydronephrosis. Methods A total of 72 Wistar rats within 48 h of newborn were selected and randomly divided into 6 groups with 12 rats in each group. One group was randomly selected as the control group， the other 5 groups were all made into animal models of partial obstruction of the left ureter. The structural changes of the diseased kidney tissues were observed by HE staining and the pathological grades of the diseased kidney tissues were made accordingly. The expression of TGF-β1， MCP-1， IGF-1 and ET-1 in kidney tissue of Wistar rats were detected by immunohistochemical SP method. Results At 12 weeks after the obstruction was relieved， the protein expression of TGF-β1 in the model group was not significantly different from that in the control group （P>0.05）. The expression of ET-1 and MCP-l protein in the model group （6.20±1.16， 3.34±0.06） were higher than those in the control group （2.27±0.73， 0.71±0.25）， the differences were statistically significant （P<0.05）. The expression of IGF-1 protein in model group （18.12±1.08） was lower than that in control group （28.38±4.82）， and the difference was statistically significant （P<0.05）. Compared with the expression of TGF-β1 protein in all pathological grades （grade Ⅰ， Ⅱ， Ⅲ， Ⅳ） in the model group， the differences were statistically significant （P<0.05）. The expression of ET-1 and MCP-1 protein in model group Ⅱ newborn mices were not significantly different from those in model group Ⅰ （P>0.05）. The expression of ET-1 and MCP-1 protein in model group Ⅲ and Ⅳ were significantly higher than those in model group Ⅱ， the differences were statistically significant （P<0.05）. The expression of IGF-1 protein in model group Ⅱ， Ⅲ and Ⅳ newborn mices were lower than those in grade Ⅰ， while the expression of IGF-1 protein in model group Ⅳ newborn mices were lower than that in grade Ⅲ， the differences were statistically significant （P<0.05）. The expression of IGF-1 protein in model group Ⅱ newborn mices had no significant difference compared with grade Ⅲ （P>0.05）. Comparison of protein expressions about TGF-β1， MCP-l， ET-1 and IGF-1 at different time points after obstruction were relieved. The expression of TGF-β1， MCP-l， ET-1 protein in the model group were lower than 2 weeks after the obstruction were relieved， and the expression of IGF-1 protein was higher than 2 weeks after the obstruction were relieved， the differences were statistically significant （P<0.05）. In the model group， the expression of TGF-β1， MCP-l， ET-1， IGF-1 protein at 2 weeks after obstruction were relieved were not significantly different from that at 0 weeks after obstruction were relieved （P>0.05）. The expression of TGF-β1， MCP-l， ET-1， IGF-1 protein in the model group at 8 weeks after obstruction were relieved were not significantly different from those at 6 weeks after obstruction were relieved （P>0.05）. The expression of TGF-β1， MCP-l， ET-1 protein in model group were lower than those in 8 weeks after obstruction were relieved， and the expression of IGF-1 protein was higher than that in 8 weeks after obstruction were relieved， the differences were statistically significant （P<0.05）. The protein expression of TGF-β1 was positively correlated with pathological grade （r=0.873， P<0.01）. The protein expressions of ET-1 and MCP-1 were positively correlated with pathological grade （r=0.579， 0.637， P<0.05）. There was no significant correlation between IGF-1 protein expression and pathological grade （P>0.05）. Conclusion Histopathological changes of diseased kidney tissue gradually recover with the extension of obstruction relieving time. The expression of TGF-β1 protein level increases with the increase of pathological grade of obstruction， and gradually decreases with the extension of time to relieve obstruction. TGF-β1 can be used as a reliable index to judge the degree of renal damage and recovery of hydronephrosis in newborn rats.