ABSTRACT
Objective:To observe the protective effect of Angong Niuhuang pill on brain function of rats with sepsis, explore its protective mechanism, and provide the experimental basis for clinical application of Angong Niuhuang pill in the treatment of sepsis-associated encephalopathy (SAE).Methods:Thirty male Sprague-Dawley (SD) rats were divided into sham operation group, sepsis model group and Angong Niuhuang pill group according to random number table method, with 10 rats in each group. The sepsis model was established by cecal ligation and puncture (CLP); rats in sham operation group received open and closed abdomen. The rats in the Angong Niuhuang pill group were given Angong Niuhuang pill (0.3 g/kg) by gastric irrigation daily for 3 days before CLP, and the drugs were administrated 12 hours after modeling again. After 24 hours of CLP, the neuroreflex scores were evaluated, white blood cell count (WBC), the levels of serum neuron-specific enolase (NSE) and S100β were detected. Then the brain tissue was harvested. After hematoxylin-eosin (HE) staining, the pathological changes of brain tissue were observed under the light microscope. The mRNA expressions of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in brain tissue were detected by polymerase chain reaction.Results:Compared with the sham operation group, the total score of neuroreflex scores in the sepsis model group and the Angong Niuhuang pill group were significantly reduced (4.43±1.40, 6.57±1.90 vs. 9.40±0.84, both P < 0.05), WBC, serum NSE, S100β were significantly increased [WBC (×10 9/L): 8.07±1.32, 5.84±0.94 vs. 3.60±0.32; NSE (μg/L): 1.04±0.14, 0.61±0.07 vs. 0.16±0.04; S100β (ng/L): 255.624±30.25, 97.72±15.41 vs. 46.88±12.03, all P < 0.05], and the mRNA expressions of IL-6 and TNF-α in brain tissue were significantly increased [IL-6 mRNA (2 -ΔΔCt): 5.668±2.195, 3.605±1.014 vs. 0.997±0.329; TNF-α mRNA (2 -ΔΔCt): 18.996±0.913, 1.746±0.710 vs. 0.674±0.132, all P < 0.05]. Compared with the sepsis model group, the total score of neuroreflex scores in the Angong Niuhuang pill group was significantly increased (6.57±1.90 vs. 4.43±1.40, P < 0.05), WBC, serum NSE, S100β concentration, and the mRNA expressions of IL-6 and TNF-α in the brain were significantly reduced [WBC (×10 9/L): 5.84±0.94 vs. 8.07±1.32, NSE (μg/L): 0.61±0.07 vs. 1.04±0.14, S100β (ng/L): 97.72±15.41 vs. 255.62±30.25, IL-6 mRNA (2 -ΔΔCt): 3.605±1.014 vs. 5.668±2.195, TNF-α mRNA (2 -ΔΔCt): 1.746±0.710 vs. 18.996±0.913, all P < 0.05]. Brain histopathological observation showed that the hippocampal neurons in the sepsis model group were disordered arrangement, a large number of neuronal nuclei were contracted, and the tissue was loose with obvious edema. Compared with the sepsis model group, the Angong Niuhuang pill group had less nuclear shrinkage and tissue edema. Conclusions:The pretreatment of the Angong Niuhuang pill can improve the brain dysfunction of septic rats and reduce the expression of pro-inflammatory cytokines in the brain. It is speculated that the Angong Niuhuang pill can protect the brain function in sepsis by inhibiting the inflammatory reaction in the brain.
ABSTRACT
Objective To investigate the diagnostic value of neuron-specific enolase(NSE),central nervous system specific protein (S100β),interleukin-6 (IL-6) in sepsis-associated encephalopathy (SAE).Methods Clinical data of patients admitted to ICU and diagnosed with sepsis were collected from January 2015 to June 2016 in Xiangya Hospital,Central South University.SAE was defined as cerebral dysfunction in the presence of sepsis that also fulfilled the exclusion criteria.The acute physiology and chronic health score (APACHE Ⅱ),sequential organ failure assessment (SOFA),NSE,S100β,IL-6,ICU stay time and 28-day mortality were compared between the two groups.NSE,S1003 and IL-6 were measured on the 1 st and 3rd day in ICU to determine the optimal cut-off value of SAE.Results Among 59 enrolled patients,36 were assigned to SAE group while 23 were non-SAE group.The SAE group had a significantly higher APACHE Ⅱ and SOFA scores,as well as the length of ICU stay (P ＜ 0.01).The levels of NSE,S1003 and IL-6 in the two groups both increased on the 1st day,and decreased on the 3rd day.The level of NSE on the 1st day [19.28 (13.00,30.52) μg/L vs 16.61 (7.58,22.01 μg/L)] and the 3rd day[16.03 (9.40,21.29) μg/L vs 11.39(8.49,15.00) μg/L,P=0.029],IL-6 on the 1st day[676.25(81.34,5 000.00) mg/L vs [209.10(42.27,648.20) mg/L,P =0.005] and the 3rd day [157.10 (72.85,687.63) mg/L vs 55.92 (31.62,177.00) mg/L,P =0.026] of SAE group was significantly higher than those of non-SAE group.However S100β between groups on the 1st day [0.33(0.15,0.54) μg/L vs 0.23(0.16,0.53) μg/L] and the 3rd day[0.19(0.10,0.29) μg/L vs 0.10(0.05,0.17) μg/L] was neither significant (P ＞0.05).The diagnostic values for SAE of NSE,S1003 and IL-6 were 14.36 μg/L,0.14 μg/L and 91.305 mg/L with sensitivity 61.1％,61.1％,72.2％ and specificity 73.9％,69.6％,69.6％,respectively.The diagnostic AUC of NSE and IL-6 combination was 0.774,95％ CI 0.651-0.896.Conclusion All sepsis patients have different degrees of brain injury.NSE combined with IL-6 on the 3rd day in ICU demonstrates the diagnostic significance of SAE.
ABSTRACT
Objective To investigate the diagnostic value of neuron-specific enolase(NSE),central nervous system specific protein (S100β),interleukin-6 (IL-6) in sepsis-associated encephalopathy (SAE).Methods Clinical data of patients admitted to ICU and diagnosed with sepsis were collected from January 2015 to June 2016 in Xiangya Hospital,Central South University.SAE was defined as cerebral dysfunction in the presence of sepsis that also fulfilled the exclusion criteria.The acute physiology and chronic health score (APACHE Ⅱ),sequential organ failure assessment (SOFA),NSE,S100β,IL-6,ICU stay time and 28-day mortality were compared between the two groups.NSE,S1003 and IL-6 were measured on the 1 st and 3rd day in ICU to determine the optimal cut-off value of SAE.Results Among 59 enrolled patients,36 were assigned to SAE group while 23 were non-SAE group.The SAE group had a significantly higher APACHE Ⅱ and SOFA scores,as well as the length of ICU stay (P ＜ 0.01).The levels of NSE,S1003 and IL-6 in the two groups both increased on the 1st day,and decreased on the 3rd day.The level of NSE on the 1st day [19.28 (13.00,30.52) μg/L vs 16.61 (7.58,22.01 μg/L)] and the 3rd day[16.03 (9.40,21.29) μg/L vs 11.39(8.49,15.00) μg/L,P=0.029],IL-6 on the 1st day[676.25(81.34,5 000.00) mg/L vs [209.10(42.27,648.20) mg/L,P =0.005] and the 3rd day [157.10 (72.85,687.63) mg/L vs 55.92 (31.62,177.00) mg/L,P =0.026] of SAE group was significantly higher than those of non-SAE group.However S100β between groups on the 1st day [0.33(0.15,0.54) μg/L vs 0.23(0.16,0.53) μg/L] and the 3rd day[0.19(0.10,0.29) μg/L vs 0.10(0.05,0.17) μg/L] was neither significant (P ＞0.05).The diagnostic values for SAE of NSE,S1003 and IL-6 were 14.36 μg/L,0.14 μg/L and 91.305 mg/L with sensitivity 61.1％,61.1％,72.2％ and specificity 73.9％,69.6％,69.6％,respectively.The diagnostic AUC of NSE and IL-6 combination was 0.774,95％ CI 0.651-0.896.Conclusion All sepsis patients have different degrees of brain injury.NSE combined with IL-6 on the 3rd day in ICU demonstrates the diagnostic significance of SAE.