| Background and ObjectiveThe concept vascular cognitive impairment is a kind of development of vascular dementia, which includes all of the cognitive changes that correlate with vascular.Chronic cerebral ischemia is one of the most important reason that causes vascular cognitive impairment. Investigation shows that ischemic is one of the most intensive stimulation that causes apoptosis. Many genes were induced expression by cerebral ischemia, some of proteins induced by which participate in regulation of apoptosis straight or indirect, like Bax,Bcl-xS,Bad,Caspases, NF-κB,P53,Fas/FasL promote apoptosis, but Bcl-2,Bcl-xL,HSP,C-fos,sFas suppress apoptosis. STAT1 (signal transducer and activator of transcription1)is a member of STATs, which is a new cytokine cell signaling pathway. It has been confirmed that this pathway widely take part in cell proliferation, differentiation, apoptosis, immunomodulation, and so on. Some research in animal model exhibited that STAT1 has indirect effect in promote apoptosis.Based on the reseach above. This experiment observe the expression of STAT1 and P-S727-STAT1 in 2VO rats the model of VCI. Through investigation of the expression of STAT1 and p-STAT1 in neuron, we tried to approach the roles of STAT1 in neuron apoptosis during the course of VCI. This experiment offer experimental evidence for clinical diagnosis and therapy.Materials and Methods1. Animals and groupsHealth SD rats was divided into 3 group; 2w group; 4w group; 8w group. Every group includes normal group, sham operated group, model group;2. Model manufactureWe blunt dissected bilateral common carotid arteries of rats of all sham operated and model groups permanently. Then we tied up bilateral common carotid arteries with 4 suture silk and shear at the middle. We separated bilateral common carotid arteries but did not deligate. All of the rats were feed in ordinary condition;3. Specimen manufactureWe decapitate the rats rapidly and take the brains after perfusing heart at the times 2w, 4w, 8w. Then we treated with ormalin fixation and made them into paraffin section , then reserved;4. Observation Index(1) Rats' memory ability was estimated by Morris water maze after being made model and before kill;(2) Observation the expression of STAT1 and P-S727-STAT1 by immunohistochemistry;(3) Detected the neuronic apoptosis by TUNEL fluorescence double labeling.;(4) Detected the expression of STAT1 and and P-S727-STAT1 by Laser Scanning Confocal Microscope;5. Statistical methodAll the measurement deta was expression by mean±standard deviation ( X|-±s) data was processed by spss13.0. one-way ANOVA was used in multi-group comparison. LSD was used between two groups. Examination standard was set atα =0.05;Results1. General state of animalsAll rats was depressed, clumsy, and intake decreased;2. Spatial memories abilityWe discovered by observing memory ability of rats with Morris water maze that the learning and memory ability ofmodel rats were impared (P<0.05 ) ;3. Obserbation the expression of STAT1 and P-S727-STAT1 by immunohistochemistryCompared with normal groups, the expression of STAT1 and P-S727-STAT1 increased in all the model groups(P<0.05);4. Detection of neurone apoptosisThe amount of apoptosis neurone is small in normal groups than those in model groups(P<0.05);5. Laser Scanning Confocal Microscope result of STAT1 and P-S727-STAT1Compared with normal groups, the expression of STAT1 and P-S727-STAT1 in neurone increased in all the model groups (P<0.05);6. The correlation between neurone apoptosis with the expression of STAT1 and P-S727-STAT1The expression of P-S727-STAT1 in neurone of all groups has positive correlation with the neuronic apoptosis.Conclusions1. The expression of STAT1 and P-S727-STAT1 is apparent at each group after cerebral ischemia;2. Neuronic apoptosis exist at each group after cerebral ischemia;3. The phosphorylation of STAT1 is correlated with neurone apoptosis, we presume that the phosphorylation of STAT1 participate in the Neuronic apoptosis during the course of VCI.
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