The Affiliated Rehabilitation Hospital, Chongqing Medical University, Chongqing, P. R. China.
Department of Cardiology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, P. R. China.
PLoS One. 2024 Jul 25;19(7):e0306137. doi: 10.1371/journal.pone.0306137. eCollection 2024.
Hypertensive nephropathy (HN) is one of the main causes of end-stage renal disease (ESRD), leading to serious morbidity and mortality in hypertensive patients. However, existing treatment for hypertensive nephropathy are still very limited. It has been demonstrated that aerobic exercise has beneficial effects on the treatment of hypertension. However, the underlying mechanisms of exercise in HN remain unclear.
The spontaneously hypertensive rats (SHR) were trained for 8 weeks on a treadmill with different exercise prescriptions. We detected the effects of moderate intensity continuous training (MICT) and high intensity interval training (HIIT) on inflammatory response, renal function, and renal fibrosis in SHR. We further investigated the relationship between TLR4 and the NLRC4 inflammasome in vitro HN model.
MICT improved renal fibrosis and renal injury, attenuating the inflammatory response by inhibiting TLR4/NF-κB pathway and the activation of NLRC4 inflammasome. However, these changes were not observed in the HIIT group. Additionally, repression of TLR4/NF-κB pathway by TAK-242 inhibited activation of NLRC4 inflammasome and alleviated the fibrosis in Ang II-induced HK-2 cells.
MICT ameliorated renal damage, inflammatory response, and renal fibrosis via repressing TLR4/NF-κB pathway and the activation of NLRC4 inflammasome. This study might provide new references for exercise prescriptions of hypertension.
高血压肾病（HN）是终末期肾病（ESRD）的主要原因之一，导致高血压患者的发病率和死亡率很高。然而，现有的高血压肾病治疗方法仍然非常有限。已经证明，有氧运动对高血压的治疗有有益的作用。然而，运动对 HN 的潜在机制尚不清楚。
我们对自发性高血压大鼠（SHR）进行了 8 周的跑步机训练，并采用了不同的运动方案。我们检测了中等强度持续训练（MICT）和高强度间歇训练（HIIT）对 SHR 炎症反应、肾功能和肾纤维化的影响。我们进一步研究了 TLR4 和 NLRC4 炎症小体在体外 HN 模型中的关系。
MICT 通过抑制 TLR4/NF-κB 通路和 NLRC4 炎症小体的激活，改善了肾纤维化和肾损伤，减轻了炎症反应。然而，在 HIIT 组中没有观察到这些变化。此外，TAK-242 抑制 TLR4/NF-κB 通路抑制了 Ang II 诱导的 HK-2 细胞中 NLRC4 炎症小体的激活，并减轻了纤维化。
MICT 通过抑制 TLR4/NF-κB 通路和 NLRC4 炎症小体的激活，改善了肾损伤、炎症反应和肾纤维化。这项研究可能为高血压的运动方案提供新的参考。
