Graduate Center for Nutritional Sciences, Univ. of Kentucky, Lexington, KY 40536, USA.
Am J Physiol Renal Physiol. 2012 Mar 1;302(5):F561-70. doi: 10.1152/ajprenal.00355.2011. Epub 2011 Dec 7.
cGMP-dependent protein kinase (PKG) is a multifunctional protein. Whether PKG plays a role in ischemia-reperfusion-induced kidney injury (IRI) is unknown. In this study, using an in vivo mouse model of renal IRI, we determined the effect of renal IRI on kidney PKG-I levels and also evaluated whether overexpression of PKG-I attenuates renal IRI. Our studies demonstrated that PKG-I levels (mRNA and protein) were significantly decreased in the kidney from mice undergoing renal IRI. Moreover, PKG-I transgenic mice had less renal IRI, showing improved renal function and less tubular damage compared with their wild-type littermates. Transgenic mice in the renal IRI group had decreased tubular cell apoptosis accompanied by decreased caspase 3 levels/activity and increased Bcl-2 and Bag-1 levels. In addition, transgenic mice undergoing renal IRI demonstrated reduced macrophage infiltration into the kidney and reduced production of inflammatory cytokines. In vitro studies showed that peritoneal macrophages isolated from transgenic mice had decreased migration compared with control macrophages. Taken together, these results suggest that PKG-I protects against renal IRI, at least in part through inhibiting inflammatory cell infiltration into the kidney, reducing kidney inflammation, and inhibiting tubular cell apoptosis.
环磷酸鸟苷依赖的蛋白激酶（PKG）是一种多功能蛋白。PKG 是否在缺血再灌注诱导的肾损伤（IRI）中发挥作用尚不清楚。在这项研究中，我们使用体内小鼠肾 IRI 模型，确定了肾 IRI 对肾脏 PKG-I 水平的影响，并评估了 PKG-I 的过表达是否减轻了肾 IRI。我们的研究表明，发生肾 IRI 的小鼠肾脏中的 PKG-I 水平（mRNA 和蛋白）显著降低。此外，与野生型同窝仔相比，PKG-I 转基因小鼠的肾 IRI 程度较轻，表现为肾功能改善，肾小管损伤减少。肾 IRI 组的转基因小鼠的肾小管细胞凋亡减少，同时 caspase 3 水平/活性降低，Bcl-2 和 Bag-1 水平升高。此外，发生肾 IRI 的转基因小鼠的肾脏中巨噬细胞浸润减少，炎症细胞因子的产生减少。体外研究表明，与对照巨噬细胞相比，从转基因小鼠分离的腹腔巨噬细胞的迁移减少。综上所述，这些结果表明 PKG-I 可预防肾 IRI，至少部分是通过抑制炎症细胞浸润肾脏、减轻肾脏炎症和抑制肾小管细胞凋亡来实现的。
