Department of Cardiology, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, Shandong, China.
Department of Neurosurgery, The First Affiliated Hospital of Shandong First Medical University, Jinan, Shandong, China.
Hypertens Res. 2020 Nov;43(11):1182-1191. doi: 10.1038/s41440-020-0471-8. Epub 2020 May 21.
Hypertension associated with hyperhomocysteinemia (HHcy) is associated with a high risk of vascular diseases. However, the mechanisms of HHcy-associated hypertensive renal damage and the efficacy of folic acid (FA) as a treatment have not been fully elucidated. The aim of the present study was to evaluate whether lowering the plasma homocysteine (Hcy) level using different doses of FA can reduce HHcy-associated glomerular injury in spontaneously hypertensive rats (SHRs) and to clarify the potential mechanisms of such effects. SHRs were randomized into a control group, HHcy group, HHcy + low-dose FA (LFA) group, and HHcy + high-dose FA (HFA) group. Compared with the control group, the HHcy group had reduced serum superoxide dismutase and GFR levels and elevated serum malondialdehyde and urinary albumin creatinine ratio levels. Increased extracellular matrix of the glomerulus and an increased glomerular sclerosis index, podocyte foot process effacement and fusion, as well as increased podocyte apoptosis, were observed in the HHcy group compared with the control group; these effects were associated with increased expression of NOX2 and NOX4 and decreased nephrin expression in renal tissue from SHRs with HHcy. HHcy-induced changes were counteracted by LFA and HFA treatment. Apart from lower levels of NOX2 in the HHcy + HFA group, there were no significant differences in other indicators between the HHcy + LFA and HHcy + HFA groups. These results suggest that even at a low dose, FA can reduce plasma Hcy and attenuate HHcy-induced glomerular injury by inhibiting oxidative stress and apoptosis.
高血压伴高同型半胱氨酸血症（HHcy）与血管疾病风险增加相关。然而，HHcy 相关高血压性肾损伤的机制以及叶酸（FA）作为治疗方法的疗效尚未完全阐明。本研究旨在评估使用不同剂量的 FA 降低血浆同型半胱氨酸（Hcy）水平是否可以减轻自发性高血压大鼠（SHR）中 HHcy 相关的肾小球损伤，并阐明这种作用的潜在机制。SHR 被随机分为对照组、HHcy 组、HHcy+低剂量 FA（LFA）组和 HHcy+高剂量 FA（HFA）组。与对照组相比，HHcy 组的血清超氧化物歧化酶和肾小球滤过率水平降低，而血清丙二醛和尿白蛋白肌酐比值水平升高。与对照组相比，HHcy 组的肾小球细胞外基质增加，肾小球硬化指数增加，足细胞足突消失和融合增加，以及足细胞凋亡增加；这些作用与 SHR 肾组织中 NOX2 和 NOX4 表达增加以及nephrin 表达减少有关。LFA 和 HFA 治疗可拮抗 HHcy 诱导的变化。除 HHcy+HFA 组中 NOX2 水平较低外，HHcy+LFA 组和 HHcy+HFA 组之间的其他指标无显著差异。这些结果表明，FA 即使在低剂量下也可以通过抑制氧化应激和细胞凋亡来降低血浆 Hcy 并减轻 HHcy 诱导的肾小球损伤。
