Cha Seung Ah, Park Byung Mun, Jung Yu Jin, Kim Soo Mi, Kang Kyung Pyo, Kim Won, Kim Suhn Hee
Department of Physiology, Chonbuk National University Medical School, Jeonju, Republic of Korea.
Internal Medicine, Chonbuk National University Medical School, Jeonju, Republic of Korea.
Peptides. 2015 Jul;69:33-9. doi: 10.1016/j.peptides.2015.03.026. Epub 2015 Apr 6.
To understand the pathophysiology of ischemia/reperfusion (I/R) - induced acute kidney injury (AKI), the present study defined changes in renal function, plasma renotropic hormones and its receptors in the kidney 2, 5, or 7 days after 45 min-renal ischemia in rats. Blood urea nitrogen, plasma creatinine, and osmolarity increased 2 days after I/R injury and tended to return to control level 7 days after I/R injury. Decreased renal function tended to return to control level 5 days after I/R injury. However, plasma concentrations of atrial natriuretic peptide and renin did not change. In control kidney, natriuretic peptide receptor (NPR)-A, -B and -C mRNAs were highly expressed in medulla (ME), inner cortex (IC), and outer cortex (OC), respectively, and tonicity-responsive enhancer binding protein (TonEBP), auqaporin-2 (AQP-2) and eNOS mRNAs were highly expressed in ME. NPR-A and -B mRNA expressions were markedly decreased 2 days after I/R injury. On 5 days after I/R injury, NPR-A mRNA expression increased in OC and recovered to control level in IC but not in ME. NPR-B mRNA expression was increased in OC, and recovered to control level in IC and ME. NPR-C mRNA expression was markedly decreased in OC 2 and 5 days after I/R injury. TonEBP, APQ-2 and eNOS mRNA expressions were markedly decreased 2 days after I/R injury and did not recover in ME 7 days after I/R injury. Therefore, we suggest that there is a regional heterogeneity of regulation of renal NPRs, TonEBP, and APQ-2 mRNA in AKI.
为了解缺血/再灌注(I/R)诱导的急性肾损伤(AKI)的病理生理学,本研究确定了大鼠肾缺血45分钟后2、5或7天肾功能、血浆促肾激素及其在肾脏中的受体的变化。I/R损伤后2天血尿素氮、血浆肌酐和渗透压升高,I/R损伤后7天趋于恢复至对照水平。肾功能下降在I/R损伤后5天趋于恢复至对照水平。然而,血浆心房利钠肽和肾素浓度未发生变化。在对照肾脏中,利钠肽受体(NPR)-A、-B和-C mRNA分别在髓质(ME)、内皮质(IC)和外皮质(OC)中高表达,而渗透压反应增强子结合蛋白(TonEBP)、水通道蛋白-2(AQP-2)和内皮型一氧化氮合酶(eNOS)mRNA在ME中高表达。I/R损伤后2天NPR-A和-B mRNA表达明显降低。I/R损伤后5天,OC中NPR-A mRNA表达增加,IC中恢复至对照水平,但ME中未恢复。OC中NPR-B mRNA表达增加,IC和ME中恢复至对照水平。I/R损伤后2天和5天OC中NPR-C mRNA表达明显降低。I/R损伤后2天TonEBP、APQ-2和eNOS mRNA表达明显降低,I/R损伤后7天ME中未恢复。因此,我们认为AKI中肾NPRs、TonEBP和APQ-2 mRNA的调节存在区域异质性。