ABSTRACT
Objective:To investigate the effect of sodium butyrate (NaB) on renal and intestinal injury after cardiac arrest and cardiopulmonary resuscitation (CA-CPR) and its related mechanism.Methods:Twenty-four domestic healthy male swines were randomly divided into 3 groups: sham group ( n=6), CA-CPR group ( n=10) and NaB group ( n=8). The animals only underwent operational preparation in the sham group. The animal model of CA and CPR was established by 9 min of ventricular fibrillation induced by electrical stimulation in the ventricle and then 6 min of CPR in the CA-CPR and NaB groups. At 5 min after resuscitation, a dose of 75 mg/kg of NaB was intravenously infused for 1 h in the NaB group, and meanwhile the same volume of vehicle was intravenously infused in the sham and CA-CPR groups. At 1, 2, 4, and 24 h after resuscitation, blood samples were collected to detect the renal and intestinal injury biomarkers, such as creatinine (Cr), blood urea nitrogen (BUN), intestinal fatty acid binding protein (IFABP), and diamine oxidase (DAO). At 24 h after resuscitation, renal and intestinal tissue specimens were harvested to detect the protein markers of cell autophagy including microtubule-associated protein light chain 3 Ⅱ (LC3Ⅱ) and p62 expression, and also renal and intestinal apoptosis. Statistical analysis was performed by SPSS software, and continuous variables were compared with one-way analysis of variance among the groups. Results:After CA-CPR, the renal and intestinal injury biomarkers including Cr, BUN, IFABP, and DAO were significantly increased at all time points after resuscitation in the CA-CPR and NaB groups compared with the sham group (all P<0.05). The injury biomarkers mentioned-above were significantly lower at all time points after resuscitation in the NaB group than in the CA-CPR group [Cr (μmol/L): (90±5) vs. (127±9) at 1 h, (135±14) vs. (168±9) at 2 h, (174±10) vs. (211±12) at 4 h, (192±10) vs. (253±13) at 24 h; BUN (mmol/L): (10.5±1.0) vs. (12.3±1.0) at 1 h, (12.2±1.2) vs. (15.3±0.9) at 2 h, (13.6±1.3) vs. (18.3±1.2) at 4 h, (15.4±1.4) vs. (21.5±1.4) at 24 h; IFABP (pg/mL): (502±33) vs. (554±32) at 1 h, (574±52) vs. (644±41) at 2 h, (646±44) vs. (732±43) at 4 h, (711±42) vs. (828±42) at 24 h; DAO (U/mL): (8.6±1.0) vs. (10.5±0.9) at 1 h, (10.6±1.2) vs. (12.8±1.0) at 2 h, (12.1±1.0) vs. (15.0±1.0) at 4 h, (14.1±1.1) vs. (17.6±1.0) at 24 h, (all P<0.05)]. Renal and intestinal tissue detection indicated that cell autophagy and apoptosis were significantly increased after resuscitation in the CA-CPR and NaB groups compared with the sham group, which was indicated by significantly increased LC3Ⅱ and decreased p62 expression, and markedly elevated apoptosis index (all P<0.05). However, cell autophagy and apoptosis in the kidney and intestine were significantly milder after resuscitation in the NaB group than in the CA-CPR group [renal LC3 Ⅱ: (1.15±0.17) vs. (2.23±0.31), p62: (1.60±0.10) vs. (1.17±0.08), apoptosis index (%): (21.2±5.3) vs. (50.9±7.9); intestinal LC3 Ⅱ: (1.03±0.17) vs. (1.71±0.21), p62: (1.30±0.29) vs. (0.79±0.29), apoptosis index (%): (25.6±6.1) vs. (61.7±10.7), all P<0.05]. Conclusions:NaB could alleviate the severity of renal and intestinal damage after CA-CPR in swine, and its protective mechanism may be related to the inhibition of cell autophagy and apoptosis.