Jing Zhang1, Mingjun Zhu1, Shiyu Zhang1, Shiyang Xie1, Yuan Gao1, Youping Wang2. 1. Central Laboratory and Division of Cardiology, First Affiliated Hospital, Henan University of Traditional Chinese Medicine, Zhengzhou 450000, China. 2. Central Laboratory and Division of Cardiology, First Affiliated Hospital, Henan University of Traditional Chinese Medicine, Zhengzhou 450000, China. Electronic address: wangyp8@163.com.
Abstract
BACKGROUND: Triptolide (TP), a principal bioactive component of traditional Chinese medicine Tripterygium wilfordii Hook. F., has been shown to have immunosuppressive/anti-inflammatory actions in vitro. Moreover, it is well established that inflammatory mechanisms contribute to the progression of hypertension-induced renal injury. Therefore, this study was performed to determine the protective effects of TP on renal injury in salt-sensitive hypertension and to identify the possible mechanisms for TP-induced protection. METHODS: Ten-week-old male C57BL/6 mice were subjected to uninephrectomy and deoxycorticosterone acetate (DOCA)-salt treatment with or without intraperitoneal administration of various concentrations of TP. RESULTS: Five weeks after the treatment, systolic blood pressure measured by tail-cuff plethysmography increased in DOCA-salt-treated mice, but no difference was found between DOCA-salt-treated mice with or without TP treatment. Treatment with TP dose-dependently attenuated increments in urinary albumin and 8-isoprostane excretion, and glomerulosclerosis and tubulointerstitial injury and fibrosis in DOCA-salt-treated mice. Moreover, our data showed that treatment with TP dose-dependently inhibited DOCA-salt-induced interstitial monocyte/macrophage infiltration associated with decreases in renal levels of proinflammatory cytokine/chemokine and adhesion molecule, as well as renal activated NF-κB concentrations. Our results also demonstrated that suppression of inflammatory responses with dexamethasone, an immunosuppressive agent, alleviated DOCA-salt hypertension-induced renal injury. CONCLUSIONS: TP treatment induced renal protection associated with inhibition of monocyte/macrophage-mediated inflammatory responses without lowering blood pressure. Thus, our data for the first time indicate that TP treatment ameliorates renal injury possibly via attenuating inflammatory responses in salt-sensitive hypertension.
BACKGROUND:Triptolide (TP), a principal bioactive component of traditional Chinese medicine Tripterygium wilfordii Hook. F., has been shown to have immunosuppressive/anti-inflammatory actions in vitro. Moreover, it is well established that inflammatory mechanisms contribute to the progression of hypertension-induced renal injury. Therefore, this study was performed to determine the protective effects of TP on renal injury in salt-sensitive hypertension and to identify the possible mechanisms for TP-induced protection. METHODS: Ten-week-old male C57BL/6 mice were subjected to uninephrectomy and deoxycorticosterone acetate (DOCA)-salt treatment with or without intraperitoneal administration of various concentrations of TP. RESULTS: Five weeks after the treatment, systolic blood pressure measured by tail-cuff plethysmography increased in DOCA-salt-treated mice, but no difference was found between DOCA-salt-treated mice with or without TP treatment. Treatment with TP dose-dependently attenuated increments in urinary albumin and 8-isoprostane excretion, and glomerulosclerosis and tubulointerstitial injury and fibrosis in DOCA-salt-treated mice. Moreover, our data showed that treatment with TP dose-dependently inhibited DOCA-salt-induced interstitial monocyte/macrophage infiltration associated with decreases in renal levels of proinflammatory cytokine/chemokine and adhesion molecule, as well as renal activated NF-κB concentrations. Our results also demonstrated that suppression of inflammatory responses with dexamethasone, an immunosuppressive agent, alleviated DOCA-salthypertension-induced renal injury. CONCLUSIONS:TP treatment induced renal protection associated with inhibition of monocyte/macrophage-mediated inflammatory responses without lowering blood pressure. Thus, our data for the first time indicate that TP treatment ameliorates renal injury possibly via attenuating inflammatory responses in salt-sensitive hypertension.