Effect of intensive insulin therapy on high mobility group box-1/nuclear factor-ΚB pathway in severe traumatic brain injury patient with stress hyperglycemia

Abstract

To explore the effect of intensive insulin therapy (IIT) on high mobility group box-1/nuclear factor-ΚB (HMGB1/NF-ΚB) signaling pathway in severe traumatic brain injury (sTBI) patient with stress hyperglycemia. Sixty-one sTBI patients with stress hyperglycemia [Glasgow coma scale (GCS) ≤ 8, three times of random blood glucose levels > 11.1 mmoL/L, glycosylated hemoglobin (HbA1c) < 0.065] admitted to the Affiliated Huaian No.1 People's Hospital of Nanjing Medical University from July 2015 to October 2017 were enrolled. Patients were divided into IIT group (29 cases, keeping blood glucose at 4.4-7.8 mmol/L) and conventional glycemic therapy (CGT) group (32 cases, keeping blood glucose at 7.8-12.2 mmo/L) according to the random number table method. Before treatment and 1, 7 and 14 days after treatment, the levels of plasma HMGB1 and tumor necrosis factor-α (TNF-α) were measured by enzyme linked immunosorbent assay (ELISA); C-reactive protein (CRP) was determined by automatic biochemical analyzer, and NF-ΚB p65 gene expression in peripheral blood mononuclear cells was detected by real-time quantitative polymerase chain reaction (PCR). Nine patients were withdrawn from the observation because the 4 consecutive blood glucose monitoring did not reach the target value, combined with severe infection, or abandoned the treatment with serious brain damage. Finally, 52 patients were enrolled in the analysis, including 28 in CGT group and 24 in IIT group. The levels of plasma HMGB1, TNF-α, CRP and the expression of NF-ΚB gene in monocytes of the two groups at 1 day after treatment were significantly higher than those before treatment, and reached the peak value, then gradually decreased. After 7 days of treatment, they were significantly lower than 1 day. The levels of plasma CRP and TNF-α in the IIT group were significantly lower than those in the CGT group [CRP (mg/L): 36.7±4.4 vs. 45.1±6.1, TNF-α (ng/L): 42.4±9.7 vs. 53.2±9.1, both P < 0.05], the level of HMGB1 in plasma and the expression of NF-ΚB p65 in monocytes were significantly lower than those in the CGT group after 14 days of treatment [HMGB1 (μg/L): 60.1±8.7 vs. 80.5±9.1, NF-ΚB p65 (ΔCt): 35.8±8.5 vs. 53.5±7.3, both P < 0.05]. IIT inhibits the inflammatory response in sTBI patients with stress hyperglycemia through HMGB1/NF-ΚB pathway.