Department of Functional Pathology, Shimane University Faculty of Medicine, Izumo, Japan.
Department of Oncology, Shimane University Faculty of Medicine, Izumo, Japan.
Biomed Res Int. 2019 Jan 16;2019:5049746. doi: 10.1155/2019/5049746. eCollection 2019.
The stroke-prone spontaneously hypertensive rat (SHRSP) suffers from severe hypertension and hypertensive organ damage such as cerebral stroke and kidney injury under salt-loading. By a quantitative trait locus (QTL) analysis between SHRSP and SHR (the stroke-resistant parental strain of SHRSP), two major QTLs for stroke susceptibility were identified on chromosomes 1 and 18 of SHRSP, which were confirmed in congenic strains constructed between SHRSP and SHR. As the progression of renal dysfunction was suggested to be one of the key factors inducing stroke in SHRSP, we examined effects of the stroke-related QTLs on kidney injury using two congenic strains harboring either of SHRSP-derived fragments of chromosomes 1 and 18 in the SHR genome. The congenic strains were challenged with 1% NaCl solution for 4 weeks; measurement of systolic blood pressure and urinary isoprostane level (a marker for oxidative stress) and evaluation of renal injury by quantification of genetic marker expression and histological examination were performed. We found that the congenic rats with SHRSP-derived fragment of chromosome 18 showed more severe renal damage with higher expression of (a genetic marker for renal fibrosis) and higher urinary isoprostane level. In contrast, the fragment of chromosome 1 from SHRSP did not give such effects on SHR. Blood pressure was not greater in either of the congenic strains when compared with SHR. We concluded that the QTL region on chromosome 18 might deteriorate salt-induced renal injury in SHR through a blood pressure-independent mechanism.
易发生中风的自发性高血压大鼠（SHRSP）在盐负荷下会出现严重的高血压和高血压器官损伤，如脑中风和肾脏损伤。通过对 SHRSP 和 SHR（SHRSP 的抗中风亲本品系）之间的数量性状基因座（QTL）分析，在 SHRSP 的第 1 和第 18 号染色体上鉴定出两个与中风易感性相关的主要 QTL，这些 QTL在 SHRSP 和 SHR 之间构建的同源系中得到了证实。由于肾功能障碍的进展被认为是 SHRSP 引起中风的关键因素之一，我们使用两种含有 SHRSP 来源的第 1 和第 18 号染色体片段的同源系，在 SHR 基因组中，检查了与中风相关的 QTL 对肾脏损伤的影响。这些同源系接受 1%NaCl 溶液处理 4 周；通过测量收缩压和尿异前列烷水平（氧化应激的标志物）以及通过遗传标记物表达的定量评估和组织学检查来评估肾脏损伤。我们发现，携带 SHRSP 第 18 号染色体衍生片段的同源系大鼠表现出更严重的肾脏损伤，其表达更高的 （肾脏纤维化的遗传标记物）和更高的尿异前列烷水平。相比之下，SHRSP 的第 1 号染色体片段并没有对 SHR 产生这样的影响。与 SHR 相比，两种同源系大鼠的血压都没有更高。我们得出结论，第 18 号染色体上的 QTL 区域可能通过与血压无关的机制恶化盐诱导的 SHR 肾脏损伤。
