Seifi Behjat, Kadkhodaei Mehri, Bakhshi Enayatollah, Sajedizadeh Abdollah, Ranjbaran Mina, Hajiaqaei Mahdi
Department of Physiology, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
Department of Statistics and Computer, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran.
Iran J Pharm Res. 2024 May 11;23(1):e145620. doi: 10.5812/ijpr-145620. eCollection 2024 Jan-Dec.
To investigate the mechanisms of exercise therapeutics in preclinical animal models of chronic kidney disease (CKD), PAG (D, L-propargylglycine), an inhibitor of hydrogen sulfide production, was used to examine the protective effects of physical activity on oxidative stress and inflammation levels during CKD.
Male Wistar rats with CKD, induced by the 5/6 nephrectomy procedure and subjected to 8 weeks of exercise training, received injections of PAG, a cystathionine γ-lyase (CSE) inhibitor, at a dose of 19 mg/kg, i.p., twice a week during those 8 weeks. The systolic blood pressure (BP) and renal sympathetic nerve activity (RSNA) were assessed. Additionally, plasma creatinine, BUN, renal hydrogen sulfide (HS) levels, oxidative stress, and inflammatory markers were evaluated.
In the PAG group, inhibition of HS production significantly reversed the improvements in plasma creatinine, BUN, renal malondialdehyde (MDA) level, superoxide dismutase (SOD) activity, TNF-α, and IL-6 that were achieved by exercise. Additionally, high RSNA and high BP, which were also reversed in the PAG group, compared to the CKD group subjected to exercise training.
The results suggest that the improvement in BP, oxidative stress, and inflammation status by exercise in CKD may be at least partially due to CSE/HS signaling.
为了研究慢性肾脏病（CKD）临床前动物模型中运动疗法的机制，使用硫化氢生成抑制剂PAG（D，L-炔丙基甘氨酸）来检验体力活动对CKD期间氧化应激和炎症水平的保护作用。
通过5/6肾切除术诱导患有CKD的雄性Wistar大鼠，并使其接受8周的运动训练，在这8周期间，每周两次腹腔注射剂量为19mg/kg的PAG（一种胱硫醚γ-裂解酶（CSE）抑制剂）。评估收缩压（BP）和肾交感神经活动（RSNA）。此外，还评估了血浆肌酐、尿素氮、肾硫化氢（HS）水平、氧化应激和炎症标志物。
在PAG组中，HS生成的抑制显著逆转了运动所带来的血浆肌酐、尿素氮、肾丙二醛（MDA）水平、超氧化物歧化酶（SOD）活性、肿瘤坏死因子-α（TNF-α）和白细胞介素-6（IL-6）的改善。此外，与接受运动训练的CKD组相比，PAG组中较高的RSNA和较高的BP也得到了逆转。
结果表明，CKD患者通过运动改善血压、氧化应激和炎症状态可能至少部分归因于CSE/HS信号传导。
