Zhao Xuan, Hui Qing-Chen, Xu Rui, Gao Ning, Cao Ping
Department of Cardiology, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, Shandong 250014, P.R. China.
Department of Cardiology, People's Hospital of Dongying, Dongying, Shandong 257091, P.R. China.
Exp Ther Med. 2022 Jun 10;24(2):510. doi: 10.3892/etm.2022.11437. eCollection 2022 Aug.
Hypertension is a common cause of kidney injury and renal damage occurs earlier and is more serious in patients with hypertension and hyperhomocysteinaemia (HHCY). Folic acid (FA) is widely used to ameliorate the organ damage caused by HHCY. However, the effective dose of FA remains controversial and certain studies have suggested that FA increases the risk of cancer. Therefore, it is necessary to identify a safe, effective drug. Resveratrol (RSV) is a natural polyphenol antioxidant. Therefore, the present study explored the effects of RSV on renal damage in spontaneously hypertensive rats (SHRs) with HHCY and its potential underlying mechanism. SHRs were divided randomly into control, HHCY, HHCY + FA and HHCY + RSV groups. Blood pressure, plasma homocysteine, indexes of oxidative stress [serum malondialdehyde (MDA) and superoxide dismutase (SOD) levels] and indexes of renal function [glomerular filtration rate (GFR) and urinary albumin creatinine ratio (UACR)] were assessed. The mRNA and protein expression levels of nephrin and NAPDH oxidase (NOX)2 and NOX4 were detected via reverse transcription-quantitative PCR and western blotting. The results demonstrated that there was no significant difference in BP (blood pressure) among the groups, while the levels of homocysteine (HCY) in the HHCY intervention groups were significantly increased compared with the control. Both FA and RSV decreased the level of HCY, but the decrease was more obvious in the HHCY + FA group. Compared with the control the serum SOD levels and GFR were significantly decreased in the HHCY group, whereas the serum MDA levels and UACR were significantly increased. Moreover, the NOX2 and NOX4 expression levels were significantly increased, whereas those of nephrin were significantly decreased in the HHCY group. The changes caused by HHCY were significantly counteracted in both the HHCY + FA and HHCY + RSV groups and the antioxidant effect was markedly stronger in the HHCY + RSV group. In conclusion, RSV, like FA, potentially improved the renal function damage aggravated by HHCY in SHRs. Furthermore, RSV improved renal function mainly via the inhibition of oxidative stress. RSV may be a potential safe and effective treatment for HHCY-induced hypertensive renal damage.
高血压是肾损伤的常见原因,在高血压合并高同型半胱氨酸血症(HHCY)患者中,肾损害出现更早且更严重。叶酸(FA)被广泛用于改善HHCY所致的器官损害。然而,FA的有效剂量仍存在争议,且某些研究表明FA会增加癌症风险。因此,有必要确定一种安全、有效的药物。白藜芦醇(RSV)是一种天然多酚抗氧化剂。因此,本研究探讨了RSV对HHCY自发性高血压大鼠(SHR)肾损伤的影响及其潜在机制。将SHR随机分为对照组、HHCY组、HHCY + FA组和HHCY + RSV组。评估血压、血浆同型半胱氨酸、氧化应激指标[血清丙二醛(MDA)和超氧化物歧化酶(SOD)水平]以及肾功能指标[肾小球滤过率(GFR)和尿白蛋白肌酐比值(UACR)]。通过逆转录定量PCR和蛋白质印迹法检测nephrin、NAPDH氧化酶(NOX)2和NOX4的mRNA和蛋白表达水平。结果表明,各组间血压(BP)无显著差异,而HHCY干预组的同型半胱氨酸(HCY)水平较对照组显著升高。FA和RSV均降低了HCY水平,但在HHCY + FA组中降低更明显。与对照组相比,HHCY组血清SOD水平和GFR显著降低,而血清MDA水平和UACR显著升高。此外,HHCY组中NOX2和NOX4表达水平显著升高,而nephrin表达水平显著降低。HHCY + FA组和HHCY + RSV组均显著抵消了HHCY引起的变化,且HHCY + RSV组的抗氧化作用明显更强。总之,与FA一样,RSV可能改善了SHR中由HHCY加重的肾功能损害。此外,RSV主要通过抑制氧化应激改善肾功能。RSV可能是治疗HHCY诱导的高血压肾损害的一种潜在安全有效的药物。