The mechanism(s) of vascular regression in adult organs remains an unexplored gap. Irradiation to the kidney results in vascular regression and renal failure. The goal of this work was to determine molecular mechanism(s) of radiation-induced vascular regression and its mitigation by the drug lisinopril. Female WAG/RijCmcr rats received either 13 Gy X-ray irradiation, sparing one leg, or no irradiation, the latter serving as age-matched controls. Some irradiated animals received lisinopril. Kidney miRNA-seq was performed 35 days postirradiation, before symptoms of nephropathy. MicroRNA expression profiles were compared with data from humans. MicroRNA targets were predicted using TargetScan and confirmed by qRT-PCR and Western blot. Renal vascular endothelial cell density was evaluated at 100 days to confirm vascular regression. The normal rat kidney microRNA profile resembled that of humans. MiR-34a was increased >7-fold and emerged as the predominant rat microRNA altered by radiation. Expression of Jagged1, a ligand in the Notch pathway of vascular development and a target of miR-34a-5p was decreased by radiation but not in irradiated rats receiving lisinopril. Radiation decreased endothelial cells in the kidneys at 100 days, confirming vascular regression. In conclusion, the results of this study showed that radiation greatly increased miRNA34-a in rat kidneys, while lisinopril mitigated radiation-induced decrease of the Notch ligand, Jagged1, a molecular target of miRNA34-a.

成人器官中血管退化的机制仍然是一个尚未探索的空白。对肾脏的照射会导致血管退化和肾衰竭。这项工作的目标是确定辐射引起的血管消退的分子机制及其药物赖诺普利的缓解作用。雌性 WAG/RijCmcr 大鼠接受 13 Gy X 射线照射（保留一条腿）或不接受照射，后者作为年龄匹配的对照。一些受辐射的动物接受了赖诺普利。肾脏 miRNA-seq 在放射后 35 天、肾病症状出现之前进行。将 MicroRNA 表达谱与人类数据进行了比较。使用 TargetScan 预测 MicroRNA 靶点，并通过 qRT-PCR 和蛋白质印迹进行确认。100 天时评估肾血管内皮细胞密度以确认血管消退。正常大鼠肾脏的 microRNA 谱与人类相似。MiR-34a 增加了 7 倍以上，并作为主要的大鼠 microRNA 因辐射而改变。Jagged1 是血管发育 Notch 通路中的一种配体，也是 miR-34a-5p 的靶标，其表达因辐射而降低，但在接受赖诺普利的受辐射大鼠中却没有降低。100 天时，辐射减少了肾脏内皮细胞，证实了血管退化。总之，这项研究的结果表明，辐射大大增加了大鼠肾脏中的 miRNA34-a，而赖诺普利减轻了辐射引起的 Notch 配体 Jagged1（miRNA34-a 的分子靶标）的减少。