High Resolution Magnetic Resonance Imaging Observation And Mechanism Of Rosuvastatin In The Treatment Of Cerebral Infarction With Middle Cerebral Artery Atherosclerosis

Part One High resolution magnetic resonance imaging observation of rosuvastatin in the treatment of middle cerebral artery atherosclerosis cerebral infarctionObjective:Cerebral infarction is a common and frequently occurring disease,which has high disability rate and heavy social burden.At present,the treatment of cerebral infarction is limited.Lipid lowering and stable plaque is an important treatment and prevention of atherosclerotic cerebral infarction,statins are one of the main therapeutic agents,but the evaluation of the treatment of cerebral atherosclerosis has yet to be further studied.Our study aims at study of symptomatic middle cerebral artery?MCA?stenosis in patients with ischemic stroke,given rosuvastatin?10mg/d?6 months after treatment,using high resolution magnetic resonance imaging?HR-MRI?to assess the changes of middle cerebral artery atherosclerotic plaque and its effect on serum lipid,in order to observe the changes of the size,shape and composition of plaque after rosuvastatin treatment.Method:New onset ischemic stroke patients were confirmed by magnetic resonance angiography?MRA?and Transcranial Doppler ultrasound?TCD?in M1 segment of middle cerebral artery stenosis,with low density lipoprotein?LDL-C?level higher than 70mg/dl?1.8mmol/L?,but less than 250mg/dl?6.5mmol/L?.The patients were examined by HR-MRI to find out the degree of stenosis and the shape and size of the middle cerebral artery,after a long time with rosuvastatin 10mg/d treatment for 6 months,review HR-MRI to understand the changes of plaque and retest blood lipid.Results:After taking rosuvastatin for six months,underwent HR-MRI examination,2 patients with MRA showed a MCA occlusion,HR-MRI imaging showed that the lumen was blocked by plaque,enhanced visible enhancement;2 patients,MRA imaging did not change significantly,but after the HR-MRI examination we found that the plaque was more serious than before,visible obvious enhancement;there are 3 patients taking time is not up,did not review HR-MRI,but did not receive rosuvastatin when the MRA showed that MCA a localized stenosis,HR-MRI can be seen the presence of plaque in lumen,enhanced visible enhancement;7 patients blood lipid had a tendency to decrease,but the results were not statistically significant.Part Two The protective effect and mechanism of Rosuvastatin on vascular endothelial injury induced by hydrogen peroxideObjective:Cerebral infarction is a common and frequently occurring disease,which is a serious threat to human health.Atherosclerosis is the most common cause of cerebral infarction,atherosclerosis is closely related to vascular endothelial injury,rosuvastatin calcium?RS?as a first and two level prevention drug for cerebral infarction,has lipid-lowering,anti-inflammatory,antioxidant,improving endothelial function and other multiple effects.Our previous studies have found that the activation of mitochondrial calcium uniporter?MCU?after cerebral infarction,which leads to the overload of mitochondrial calcium and aggravates the damage of neurons incerebral infarction,inhibition MCU shows neuroprotective effect in the stoke model.In this study,we investigated whether rosuvastatin can alleviate the injury of human umbilical vein endothelial cells?HUVEC?induced by H₂O₂? Whether its mechanism by down-regulating the MCU thus inhibiting calcium overload and play a protective role on endothelial cells?Methods:H₂O₂ injury HUVEC model is established,synchronization of conventionally cultured HUVEC for 24 h,and divided into control group,H₂O₂ group,different concentrations of rosuvastatin?0.5?mol/L,1?mol/L,5?mol/L?early intervention 2h +H₂O₂ group,through the MTT experiment understand the effect of rosuvastain on cell viability after H₂O₂ induced HUVEC damage,and the expression of MCU m RNA in each group was detected by Real-time reverse transcription-quantitative Polymerase Chain Reaction?RT-q PCR?.Results:1 Different concentrations of rosuvastatin?0.5?mol/L,1?mol/L,5?mol/L?were treat HUVEC for 24 h,there were no significant difference in the survival rate of HUVEC compared with the control group?P>0.05?.2 Preparation of H₂O₂ induced HUVEC damage model,with the increase of H₂O₂ concentration,the cell viability was significantly reduced,compared with the control group,the cell viability decreased about 50% at 750?mol/L concentration?P<0.05?.3 Different concentrations of rosuvastatin?0.5?mol/L,1?mol/L,5?mol/L?early intervention HUVEC for 2h and then co-treatment with 750?mol/L H₂O₂ for 24 h,compared with the model group,the viability of HUVEC increased significantly with the increase of rosuvastatin concentration?P<0.05?.4 Realtime-q PCR showed that the expression of MCU m RNA in the H₂O₂ model group and rosuvastain 0.5?mol/L+H₂O₂ group was significantly higher than that control?P<0.05?,rosuvastain 1?mol/L and 5?mol/L early intervention 2h+H₂O₂group compared with the model group,its expression decreased,the rosuvastatin group 5?mol/L early intervention 2h+H₂O₂ group decreased most significantly?P<0.05?.Conclusions:1 In our study,we build up a method by HR-MRI to observe the intracranial stenosis vascular plaque,but in this study?It is a multi center study initiated by Beijing Tiantan Hospital?,due to the small number of patients involved in our case,some patients do not return time,some statistics have not yet been completed,the effect of rosuvastatin on stabilizing and reversing plaque need to further study.2 Excessive H₂O₂ can induce HUVEC damage and lead to the release of MCU,rosuvastatin can inhibit H₂O₂ induced cell death and increase the survival rate of cells,the mechanism may be though inhibition of MCU can inhibit calcium overload and play a role of endothelial cell protection.