ABSTRACT
Objective To investigate the effect and mechanism of metformin on inflammatory cytokines after cerebral ischemia-reperfusion injury in rats.Methods A rat model of middle cerebral artery occlusion (MCAO)was established by suture method.The neurological function was evaluated by modified neurological function score (mNSS).The apoptosis was detected by TUNEL method.The levels of interleukin-6 (IL-6),interleukin-8(IL-8) and tumor necrosis factor alpha (TNF-α) in serum were detected by enzyme-linked immunosorbent assay (ELISA).The expression levels of hypoxia inducible factor-1α(HIF-1α),BAX and BCL-2 protein in brain tissue was detected by Western Blot.Results Compared with the control group,the neurological function scores and the tissue cell apoptosis of the rats with cerebral ischemia injury was both significantly increased (all P＜0.01).Compared with the model group,metformin could alleviate the rats' neurological damage after cerebral ischemia-reperfusion,and the expression of IL-6,IL-8 and TNF-α in serum were significantly decreased (all P＜0.01).The expression of HIF-1α and BAX proteins were significantly down-regulated and the BCL-2 protein was up-regulated by metformin in rat brain tissue so as to regulate the expression of apoptosis-related proteins and reduce the apoptosis of brain tissue cells.Conclusions Metformin can reduce the expression of inflammatory cytokines and inhibit the apoptosis,which may play a protective role for cerebral ischemia-reperfusion injury.The mechanism may be related to the regulation of apoptosis-related protein expression,inhibition of HIF-1α expression,and inhibition of the release of related inflammatory factors TNF-α,IL-6 and IL-8.
ABSTRACT
Objective To study the changes rule of serum procalcitonin (PCT) and PCT clearance rate (PCTc) in patients with severe craniocerebral injury complicated with pulmonary infection and analyze the values of PCT and PCTc in the patients' therapeutic effect and prognosis.Methods A retrospective controlled analysis was conducted, the clinical data of 58 patients with severe craniocerebral injury complicated with pulmonary infection admitted into the Department of Neurology of the Forth Hospital of Tianjin from December 2012 to December 2016 were collected, and within 24 hours after definite diagnosis (before treatment) and after treatment for 1, 3, 7 days, the levels of PCT and percentages of PCTc were measured by rapid semi quantitative method. According to the therapeutic results of treatments, including antibiotics, airway management, nutritional support, etc., the patients were divided into an effective group and a deteriorative group. The changes rule of levels of serum PCT and percentages of PCTc before treatment and 1, 3, 7 days after treatment were dynamically evaluated. The receiver operating characteristic curve (ROC curve) was drawn and the area under the ROC curve (AUC) was calculated, and the sensitivity, specificity and diagnostic accordance rate of the combined treatment were assessed.Results Of 58 cases 32 (55.2%) after active treatment had promising therapeutic results or better prognosis (effective group), and the disease situations in 26 patients (44.8%) were deteriorating(deteriorative group). With prolonged treatment in effective group, the serum level of PCT was decreased gradually, while the deteriorative group showed a tendency firstly decreased and then increased, reaching to the valley on the 1st day after treatment, on the 3rd day beginning to increase and reaching the peak on the 7th day; the levels of PCT in effective group were significantly lower than those in deteriorative group at each time point after treatment on 1, 3, 7 days (μg/L: 1 day was 2.67±0.77 vs. 3.24±0.90, 3 days was 1.38±0.63 vs. 3.31±0.85, 7 days was 0.61±0.16 vs. 3.82±1.05, allP < 0.05); The PCTc rates in the effective group were significantly higher than those in the deteriorative group at each time point on 1, 3 and 7 d [1 day was (17.53±9.94)% vs. (12.31±7.55)%, 3 days was (60.34±13.55)% vs. (8.31±4.69)%, 7 days was (82.47±15.11)% vs. (-5.82±9.60)%, allP < 0.05]. After treatment for 3 days, 7 days, the AUC of PCT were 0.532 and 0.688, and the diagnosis cut-off values were 2.42 and 1.86 respectively; on 1, 3, 7 days after treatment, the AUC of PCTc were 0.529, 0.547, 0.775, and the diagnostic cut-off values were 15.67, 35.94 and 70.55 respectively. Further the final outcome was recognized as the gold standard: after treatment for 7 days, the PCT sensitivity was 80.1%, specificity 75%, the coincidence rate 77.6%; 7 days after treatment, the sensitivity of PCTc was 92.3%, the specificity 87.5%, the coincidencerate 89.7%.Conclusion The dynamic observations on serum PCT and PCTc have relatively good evaluation values on the therapeutic effect and prognosis of patients with severe craniocerebral injury complicated with pulmonary infection.