Feng-Zhen Lian1, Pan Cheng1, Cheng-Shao Ruan1, Xin-Xin Ling1, Xiao-Yun Wang1, Ming Pan1, Mei-Ling Chen2, Ai-Zong Shen3, Shan Gao4. 1. Department of Pharmacology, Basic Medical College, Anhui Medical University, Hefei, 230032, China. 2. Cancer Hospital, Chinese Academy of Sciences, Hefei, 230032, China. 3. The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, 230001, P.R. China. Electronic address: ahslyysaz@126.com. 4. Department of Pharmacology, Basic Medical College, Anhui Medical University, Hefei, 230032, China; Cancer Hospital, Chinese Academy of Sciences, Hefei, 230032, China. Electronic address: gaoshan@ahmu.edu.cn.
Abstract
AIM: Cardiovascular diseases, such as coronary heart disease and myocardial infarction (MI) are currently considered as the leading causes of death and disability. The aim of the present study is to investigate the effects of Xin-Ji-Er-Kang (XJEK) on kidney injury and renal oxidative stress. In addition, the associated mechanism involved in these processes was examined in an MI model, and particularly focused on the nuclear factor erythroid 2-related factor (NRF2)/heme oxygenase-1 (HO-1) pathway. MATERIALS AND METHODS: A total of 138 Sprague-Dawley rats were used in the present study. The control group was designated as 0 wk (n = 8). A total of 3 phases (2, 4, 6 wk) of administration were used in the sham-operated groups (sham, n = 10), MI groups (MI, n = 10), MI + XJEK groups (XJEK, n = 10) and MI + fosinopril groups (fosinopril, n = 10). Additional 10 rats were used to evaluate the infarct area. At 2, 4 or 6 wk post-MI, the hemodynamic parameters were monitored, the rats were sacrificed, then blood, heart and renal tissues were collected for furtherly analysis. RESULTS: The results indicated that XJEK administration continuously ameliorated renal hypertrophy index, blood urea nitrogen and cystatin C concentrations. XJEK further improved post-MI cardiac function by limiting scar formation and caused a downregulation in the hemodynamic parameters at the end of 2 and 4 wk. The hemodynamic parameters were upregulated after 6 wk treatment with XJEKcompared with those noted in the MI groups. Similarly, XJEK treatment for 2 wk potentiated Nrf2 nuclear translocation and HO-1 expression and inhibited the deficiency of nuclear Nrf2 and HO-1 at 6 wk post-MI compared with that of the MI groups, indicating the attenuation of the renal oxidative stress condition. The levels of malondialdehyde and angiotensin II (Ang II) in plasma and renal tissues, as well as the levels of aldosterone, 8-hydroxydeoxyguanosine, angiotensin II type 1 receptor and NADPH Oxidase-4 in the kidney tissue significantly decreased following XJEK treatment for 6 wk. In addition, the XJEK treatment groups revealed a significant upregulation in the activity of superoxide dismutase and in the total antioxidant capacity activity compared with those noted in the corresponding MI groups. CONCLUSION: These results demonstrated that progressive nephropathy in MI rats was associated with intrarenal activation of the renin-angiotensin-aldosterone system. Concomitantly, this process was associated with oxidative stress and impaired Nrf2 activation. The improvement in the severity of nephropathy by XJEK in this model may be associated with the reversal of these abnormalities.
AIM: Cardiovascular diseases, such as coronary heart disease and myocardial infarction (MI) are currently considered as the leading causes of death and disability. The aim of the present study is to investigate the effects of Xin-Ji-Er-Kang (XJEK) on kidney injury and renal oxidative stress. In addition, the associated mechanism involved in these processes was examined in an MI model, and particularly focused on the nuclear factor erythroid 2-related factor (NRF2)/heme oxygenase-1 (HO-1) pathway. MATERIALS AND METHODS: A total of 138 Sprague-Dawley rats were used in the present study. The control group was designated as 0 wk (n = 8). A total of 3 phases (2, 4, 6 wk) of administration were used in the sham-operated groups (sham, n = 10), MI groups (MI, n = 10), MI + XJEK groups (XJEK, n = 10) and MI + fosinopril groups (fosinopril, n = 10). Additional 10 rats were used to evaluate the infarct area. At 2, 4 or 6 wk post-MI, the hemodynamic parameters were monitored, the rats were sacrificed, then blood, heart and renal tissues were collected for furtherly analysis. RESULTS: The results indicated that XJEK administration continuously ameliorated renal hypertrophy index, blood ureanitrogen and cystatin C concentrations. XJEK further improved post-MI cardiac function by limiting scar formation and caused a downregulation in the hemodynamic parameters at the end of 2 and 4 wk. The hemodynamic parameters were upregulated after 6 wk treatment with XJEKcompared with those noted in the MI groups. Similarly, XJEK treatment for 2 wk potentiated Nrf2 nuclear translocation and HO-1 expression and inhibited the deficiency of nuclear Nrf2 and HO-1 at 6 wk post-MI compared with that of the MI groups, indicating the attenuation of the renal oxidative stress condition. The levels of malondialdehyde and angiotensin II (Ang II) in plasma and renal tissues, as well as the levels of aldosterone, 8-hydroxydeoxyguanosine, angiotensin II type 1 receptor and NADPH Oxidase-4 in the kidney tissue significantly decreased following XJEK treatment for 6 wk. In addition, the XJEK treatment groups revealed a significant upregulation in the activity of superoxide dismutase and in the total antioxidant capacity activity compared with those noted in the corresponding MI groups. CONCLUSION: These results demonstrated that progressive nephropathy in MI rats was associated with intrarenal activation of the renin-angiotensin-aldosterone system. Concomitantly, this process was associated with oxidative stress and impaired Nrf2 activation. The improvement in the severity of nephropathy by XJEK in this model may be associated with the reversal of these abnormalities.