ABSTRACT
Objective To investigate whether hydrogen-rich saline could ameliorate the expressions of cytokines in a rat model of inflammatory pain through activating heme oxygenase-1 (HO-1).Methods Eighty male Sprague-Dawley (SD) rats,weighing 180 ～ 220 g,were randomly divided into five groups (n =16 in each group):Control group (Con),inflammation pain group (CFA),inflammation pain + hydrogen-rich saline group (CFA + H2),inflammation pain + HO-1 inhibitor Znpp-Ⅸ group (CFA + Znpp-Ⅸ),and inflammation pain + hydrogen-rich saline + HO-1inhibitor Znpp-Ⅸ group (CFA + H2 + Znpp-Ⅸ).The mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL) were tested on days 1 (T1),2 (T2),3 (T3),5 (T4),7 (T5),and 14 (T6) after inflammation pain.The expressions of spinal HO-1 mRNA and protein were measured with real-time quantitative polymerase chain reaction (RT-PCR) and Western blot,and spinal inflammatory cytokines were measured with enzyme-linked immunosorbent assay (ELISA) on day 7 after inflammatory pain.Results Compared to Con group,MWT and TWL were significantly reduced;the spinal HO-1 mRNA level,protein expression and activity were increased;and the levels of tumor necrosis factor-α (TNF-α),interleukin (IL)-1β,IL-6 and IL-10 in spinal tissues were also increased in CFA group (P ＜ 0.05).Compared to CFA group,MWT and TWL were significantly increased;the spinal HO-1 mRNA level,protein expression and activity were further increased;and the levels of TNF-α,IL-1β and IL-6 were decreased,while IL-10 was further increased in CFA + H2group (P ＜ 0.05).Compared to CFA + H2 group,MWT and TWL were decreased;the spinal HO-1 mR-NA level,protein expression and activity were decreased;and the levels of TNF-α,IL-1β and IL-6 in spinal tissue were significantly increased,while IL-10 was decreased in CFA + H2 + Znpp-Ⅸ group (P ＜0.05).Conclusions Hydrogen-rich saline can ameliorate the mechanical and thermal allodynia in a rat model of inflammatory pain,and reduce the release of inflammatory cytokines via activating HO-1.
ABSTRACT
Objective To investigate the relationship and mechanism of the heme oxygenase-1 expression in peripheral blood mononuclear cells (PBMC) and the oxidative stress in diabetic nephropathy. Methods Two groups of diabetic patients with or without diabetic nephropathy and a normal control group were enrolled in this study. Fasting blood glucose (FBG), HbA1c, serum MDA level, ROS level, HO-1 mRNA level and HO-1 protein expression in PBMC were determined. Results In control group, diabetic group and diabetic nephropathy group , the MDA levels significantly increased[(14.23±5.07)nmol/ml vs (24.90±7.12)nmol/ml vs (43.83±16.97)nmol/ml](F＝37.022,P＜0.01), the ROS levels significantly increased (113.18±58.59 vs 364.54±88.67 vs 524.35±162.51)(F＝68.369,P＜0.01) and the HO-1 protein expression also increased significantly (22.84±9.98 vs 36.72±15.85 vs 58.1±15.93)(F＝31.302,P＜0.01). There was a positive correlation among the HO-1 mRNA, protein expression and MDA level(r＝0.407,0.429,P＜0.05). Conclusions There existed a severer oxidative stress condition in patients with diabetic nephropathy compared with the patients without diabetic nephropathy. HO-1 could be a potential pathway to ameliorate oxidative stress in diabetic kidney disease patients.