Effects of different low-dose of insulin glargine on antioxidation of organs in burned rats with delayed resuscitation / 中华危重病急救医学

ABSTRACT

Objective:To study the antioxidant protective effects of different low-dose of insulin glargine on organs of burned rats with delayed resuscitation.Methods:Forty male Sprague-Dawley (SD) rats were randomly divided into sham group, delayed resuscitation control group, and insulin glargine 0.5, 1.0, and 2.0 U groups, with 8 rats in each group. The rats were immersed in hot water (95.0±0.5) ℃ for 15 s to establish the third-degree scald model with 30% total body surface area. The rats in the sham group were immersed in a 37 ℃ water bath for 15 s. Insulin glargine (0.5, 1.0, 2.0 U·kg -1·d -1) was injected subcutaneously in corresponding insulin glargine group 2 hours after injury, and the same amount of normal saline was injected intraperitoneally in the delayed resuscitation control group. Intraperitoneal injection of normal saline 40 mL/kg simulated delayed resuscitation 6 hours after injury in all groups. Abdominal aortic blood samples, heart and kidney tissue were collected immediately after simulating burn in the sham group, and 24 hours after burn in other four groups. The blood glucose, myocardial enzymes [lactate dehydrogenase (LDH), creatine kinase (CK), α-hydroxybutyrate dehydrogenase (α-HBDH), and aspartate aminotransferase (AST)] and renal function indexes [blood urea nitrogen (BUN) and serum creatinine (SCr)] were measured by spectrophotometry, and the isoenzyme MB of creatine kinase (CK-MB) level was determined by immunosuppression method to evaluate the effects of different low-dose insulin glargine intervention on blood glucose, cardiac and renal functions in scalded rats with delayed resuscitation. The oxidative and antioxidant indices [xanthine oxidase (XOD), myeloperoxidase (MPO), copper-zinc superoxide dismutase (CuZn-SOD), catalase (CAT), glutathione peroxidase (GSH-Px), and total antioxidant capacity (T-AOC)] from the heart and kidney tissues of rats were detected by spectrophotometry to analyze the antioxidant effects of different low-dose insulin glargine interventions. Results:Compared with the sham group, the blood glucose of the rats in the delayed resuscitation control group was significantly increased, the heart and kidney functions were significantly reduced, the oxidation capacity was enhanced, and the antioxidant indicators were significantly reduced. After the intervention of insulin glargine, with the increase of insulin glargine dose, the blood glucose, myocardial enzyme and renal function indicators of rats showed a gradual downward trend, the oxidation indicators continued to decrease, and the antioxidant indicators showed a gradual upward trend. When the dose was 2.0 U·kg -1·d -1, the blood glucose, LDH, CK, CK-MB, α-HBDH, AST, BUN, SCr, XOD and MPO were significantly lower than those in the delayed resuscitation control group [blood glucose (mmol/L) 5.91±0.25 vs. 11.76±0.36, LDH (U/L) 3 332.12±51.61 vs. 5 008.94±490.12, CK (kU/L) 0.49±0.03 vs. 0.85±0.04, CK-MB (U/L) 125.40±12.19 vs. 267.52±11.63, α-HBDH (U/L) 122.99±5.37 vs. 240.85±13.99, AST (U/L) 11.95±1.81 vs. 17.87±1.57, BUN (mmol/L) 4.72±0.15 vs. 7.16±0.34, SCr (μmol/L) 87.11±6.51 vs. 137.50±11.36, XOD (U/g) 166.29±3.27 vs. 204.90±4.82 in heart tissue, 63.51±1.46 vs. 79.69±1.75 in kidney tissue, MPO (U/g) 1.05±0.02 vs. 1.55±0.06 in heart tissue, 1.04±0.04 vs. 1.87±0.01 in kidney tissue, all P < 0.05], and CuZn-SOD, CAT, GSH-Px and T-AOC were significantly higher than those in the delayed resuscitation control group [CuZn-SOD (kU/g) 82.95±2.69 vs. 56.52±2.26 in heart tissue, 94.50±2.73 vs. 62.02±1.66 in kidney tissue, CAT (U/g) 36.07±2.01 vs. 15.15±2.22 in heart tissue, 184.49±4.53 vs. 156.02±3.96 in kidney tissue, GSH-Px (kU/g) 231.93±8.03 vs. 179.48±3.15 in heart tissue, 239.63±7.30 vs. 172.20±2.09 in kidney tissue, T-AOC (kU/g) 4.85±0.23 vs. 2.71±0.11 in heart tissue, 5.51±0.08 vs. 3.50±0.07 in kidney tissue, all P < 0.05]. Conclusion:Different low-dose of insulin glargine (≤2.0 U·kg -1·d -1) could exert antioxidant protection on the heart and kidney of rats with delayed resuscitation after burns, with a dose-dependent manner.