1.Inhibition of Cdk5/p25 by TFP5 protects dopaminergic neurons in MPTP-induced mouse model of Parkinson's disease
Qishan ZHANG ; Renbin HUANG ; Yuangao LIAO ; Zhong JI ; Yong GU ; Suyue PAN ; Yafang HU
Chinese Journal of Behavioral Medicine and Brain Science 2015;24(12):1057-1061
Objective To study the neuroprotective role of TFP5 in a MPTP-induced mouse model of Parkinson's disease (PD).Methods C57BL/6 mice were used as experimental animals.Briefly, 5 consecutive days of intraperitoneal injection of 25 mg/Kg 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) was applied to induce mouse PD model.The mice were randomized into 5 groups including control group,model group, scrambled TFP5 peptide (Scb) group, TFP5 group and roscovitine group.On the 7th day after the first injection of MPTP,behavior tests were performed, and then western blot method was employed to detect the expression of p25 and phosphorylated MEF2D in substantia nigra.Tyrosine hydroxylase (TH) immunohistochemical staining was performed to observe the apoptosis of dopaminergic neurons in substantia nigra pars compacta (SNpc) 28 days after the first injection of MPTP.Results MPTP increased the expression of p25 (0.48±0.10 vs 0.26±0.02, P<0.05) and phosphorylated MEF2D (0.81±0.10 vs 0.22±0.02, P<0.05) in substantia nigra, but decreased the number of dopaminergic neurons in SNpc (348.67±24.40 vs 463.29± 19.61, P<0.05),resulting in motor impairment in the model mice (P<0.05).Intraperitoneal injection of 30mg/Kg of TFP5 for 3 days effectively reduced the excessive phosphorylation of MEF2D (0.25 ± 0.12 vs 0.81 ± 0.10, P< 0.05) in substantia nigra, rescued dopaminergic neuron reduction of SNpc (422.92±8.41 vs 348.67±24.40, P<0.05), and improved the motor ability of the model mice (P <0.05).Roscovitine exerted almost same neuroprotective role as TFP5 ,while Scb had no protective effect.Conclusion TFP5 can rescue MPTP-induced damage of dopaminergic neurons in substantia nigra, and thus improve motor impairment of model mice,which may be mediated by the inhibition of Cdk5/p25 activity.
2.The relationship between the level of serum lipoprotein associated phospholipase A2 and the condition and prognosis of patients with acute ischemic stroke
Limei CAO ; Bin JIANG ; Yuangao LIAO
Journal of Apoplexy and Nervous Diseases 2020;37(10):877-880
Objective To investigate the relationship between the level of Lp-PLA2 and the condition as well as prognosis of patients with acute ischemic stroke.Methods The general data of 120 patients with acute ischemic stroke and 92 healthy persons were collected.The serum Lp-PLA2 levels were detected by ELISA.NIHSS scale was used to assess the severity of the disease at admission.mRS was used to evaluate the prognosis 3 months after discharge.The correlation between serum Lp-PLA2 level and the severity of the disease was analyzed.The risk factors of prognosis were analyzed.Results The proportion of hypertension and the level of serum Lp-PLA2 in patients with acute ischemic stroke were significantly higher than those in control group (P<0.05).Among 120 patients with acute ischemic stroke,47 cases were mild,38 cases were moderate,and 35 cases were severe.There was significant difference in serum Lp-PLA2 level among the three groups (P<0.05).Pearson correlation analysis showed that serum Lp-PLA2 levels were positively correlated with NIHSS score (P<0.05).Among 120 patients with acute ischemic stroke,81 cases had good prognosis and 39 cases had poor prognosis.The age of patients in poor prognosis group was significantly longer than that in good prognosis group (P<0.05),the time from onset to admission was significantly longer than that in good prognosis group (P<0.05),and serum Lp-PLA2 levels were significantly higher than that in good prognosis group (P<0.05).Multivariate logistic regression analysis showed that age and Lp-PLA2 were risk factors for prognosis of patients with acute ischemic stroke(P<0.05).Conclusion The higher the level of Lp-PLA2,the more serious the disease is.Lp-PLA2 is a risk factor of prognosis in patients with acute ischemic stroke.