Background: Ischemia-reperfusion injury (IRI) is a major cause of acute kidney injury (AKI) and increases the risk of subsequently developing chronic kidney disease. Angiogenesis has been shown to play an important role in reducing renal injury after ischemia reperfusion. In this study, we investigated whether IMD could reduce renal IRI by promoting angiogenesis.
Methods: The kidneys of Wistar rats were subjected to 45 min of warm ischemia followed by 24 h of reperfusion. IMD was overexpressed in vivo using the vector pcDNA3.1-IMD transfected by an ultrasound-mediated system. The renal injury after ischemia reperfusion was assessed by detection of the serum creatinine concentration and histologic examinations of renal tissues stained by PAS and H&E. Real-time PCR and Western blotting were used to determine the mRNA and protein levels, respectively. Histological examinations were used to assess the expression of CD31, MMP2, MMP9, ET-1, VEGF and VEGFR2 in tissues.
Results: Renal function and renal histological damage were significantly ameliorated in IMD-transfected rats after ischemia reperfusion. Compared to the IRI, IMD significantly promoted angiogenesis. IMD also upregulated the protein and mRNA expression levels of VEGF and VEGFR2 and downregulated the expression level of MMP2, MMP9 and ET-1.
Conclusion: IMD could protect the kidney after renal ischemia-reperfusion injury by promoting angiogenesis and reducing the destruction of the perivascular matrix.



中文翻译：

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Intermedin 减轻肾缺血再灌注损伤并增强 Wistar 大鼠的新生血管形成

背景：缺血再灌注损伤 (IRI) 是急性肾损伤 (AKI) 的主要原因，并增加了随后发展为慢性肾病的风险。血管生成已被证明在减少缺血再灌注后的肾损伤中起重要作用。在这项研究中，我们研究了 IMD 是否可以通过促进血管生成来降低肾脏 IRI。
方法：对 Wistar 大鼠的肾脏进行 45 分钟的热缺血，然后再进行 24 小时的再灌注。使用由超声介导系统转染的载体 pcDNA3.1-IMD 在体内过表达 IMD。通过检测血清肌酐浓度和PAS和H&E染色的肾组织的组织学检查来评估缺血再灌注后的肾损伤。实时荧光定量 PCR 和蛋白质印迹分别用于确定 mRNA 和蛋白质水平。组织学检查用于评估组织中CD31、MMP2、MMP9、ET-1、VEGF和VEGFR2的表达。
结果：缺血再灌注后 IMD 转染的大鼠肾功能和肾组织学损伤显着改善。与IRI相比，IMD显着促进血管生成。IMD还上调VEGF和VEGFR2的蛋白和mRNA表达水平，下调MMP2、MMP9和ET-1的表达水平。
结论： IMD通过促进血管生成、减少血管周围基质的破坏，对肾缺血再灌注损伤后的肾脏具有保护作用。