| Objective:Cerebral infarction is the leading cause of death and the most common cause of adult neurologic disability.Despite of advances in acute and prophylactic, therapies,rates of cerebral infarction and cerebral infarction-related deaths continue to increase.Not only may inflammatory and immune process play a role in atherosclerosis and cerebral infarction occurrence,but it also play a critical role in postischemic injury.C-reactive protein(CRP)has been suggested as a marker for inflammatory process and seems to correlate with poor prognosis after cerebral in farction.Changes of T lymphocyte subsets in the peripheral blood have been found in patients with cerebral infarction,the clinical implication of the changes has not been known clearly.In the brains of Alzheimer's disease(AD)patients amyloid beta-peptide(Aβ)is the major component of senile plaque.Aβ(Aβ40 and Aβ42)is a proteolytic product of the larger beta amyloid precursor protein(βAPP).In the brains of AD,a cardinal role for Aβhas been postulated as a major trigger of neuronal injury,Aβcompromises neurons via an excitotoxic pathway including extracellular glutamate accumulation,N-methyl-D-aspartate(NMDA)receptor activation and an intracellular Ca2++overload leading to cell death.Aβalso appears to be associated with an inflammatory response in AD brains.In ischemic stress,βAPP and Aβwere reported to be changed.The change of Aβlevels and the biological significance of Aβin patient with ischemic stroke have not been known clearly,the interplay among various pathogenic role in the progression of cerebral infarction remains unclear.Neuroprotective agents that change the pathophysiological processes could be beneficial to patients with cerebral infarction and alter the course of the disease.Many neuroprotective drugs reduce ischemic damage in animal models of stroke,but the side effects are severe.Many are searching for a safe agent that can limit ischemic damage in human stroke.In the last few years,several studies appear to show that statins have effects that extend beyond cholesterol reduction,statins seem to be able to decrease inflammatory response,have pleiotropic immunomodulatory effects, reduce deleterious effects of excitatory neurotransmiter on cells,and have anti-oxidant effects.Some studies show that the use of statins is associated with a lower risk of developing AD.Cell and animal experiments have revealed a connection between cholesterol metabolism and the processing ofβAPP,it has been suggested thatβAPP processing is altered by statins and that leads to changes in Aβconcentration. Pleiotropic effects of statins might be implicated in any potential benefit in ischemic stroke.This implys statins might have protective effect on cerebral infarction.Studies about the role of statins in patients with cerebral infarction are few. Thus,we measured serum Aβ40,plasma Aβ42 levels,serum CRP levels, Tlymphocyte subsets in the peripheral blood,serum levels of total cholesterol(TC), triglyceride(TG),high density lipoprotein cholesterol(HDL-C)and low density lipoprotein cholesterol(LDL-C),serum aspartate aminotransferase(AST)levels and serum creatine kinase(CK)levels in acute cerebral infarction subjects before and after statins treatment.All patients were examined with National Institutes of Health Stroke Scale(NIHSS)and Barthel Index(BI)score at admission and 3 months after admission.To investigate the changes and clinical implication of serum Aβ40 and plasma Aβ42 concentration and the effect of statins intervention on former parameters and the outcome of cerebral infarction.Methods:Participant were healthy control and cerebral infarction patients.Cerebral infarction patients were consistent with the diagnosis and exclusion criteria of the study,the course of disease were no more than 2 weeks.Patients entered a randomized,placebo-controlled intervention trial.They were randomized to one of the two treatment groups for 1 week.Conventional treatment for the group of platelet inhibitors,brain protection agents and improve the circulation of drugs;The treatment perscription of statins group:20 mg/d atorvastatin plus the treatment perscription of control group.Venous blood was collected from patients with cerebral infarction after an overnight fast(12h)for all measurements at baseline and after treatment(week 1),healthy controls were measured only 1 times.Serum Aβ40 and serum Aβ42 levels were sandwich enzyme-linked irnmunosorbent assay (ELISA).Serum analysed by light rate nephelometry with the use of a automatic clinical chemistry analyzer.T lymphocyte subsets in the peripheral blood were analyzed by flow cytometry using direct immunofluoreseent labelling method.Next parameters of serum were analysed on a automatic biochemical analyzer.Serum TC and TG levels were determined by standard enzymatic method.Serum HDL-C and LDL-C concentrations were determined by 1 point method.Serum AST levels were measured by ultraviolet continuous monitoring method and serum CK levels were measured by DGKC method.All patients were examined with National Institutes of Health Stroke Scale(NIHSS)and Barthel Index(BI)score at admission(NIHSSI,BI1) and 3 months after admission(NIHSS2,B12) ll analyses were carried out using SPSSll.5 for windows(SPSS Software)Statistical significance was defined as P＜0.05.Results:1.We found that baseline and week l serum Aβ40 levels of cerebral infarction group were higher than that of control group(P＜0.01),baseline and week l serum Aβ42 levels of cerebral infarction group were lower than that of control group(P＜0.01), baseline and weeks Aβ40/Aβ42 of cerebral infarction group were higher than that of control group(P＜0.01)Week l levels of serum Aβ40 and serum Aβ42 were not different significantly compared with baseline levels in cerebral infarction group,Aβ40/Aβ42 of baseline were lower than that of week l in cerebral infarction group (P＜0.05).By regression analysis,we found that the more robust determinants for Aβ40(42) levels in cerebral infarction group were age,sex,course of disease,Aβ42(40)levels, NIHSS and B I(P＜0.05～P＜0.01).Serum Aβ40 levels had significant minus relation with age,serum Aβ42 levels and BI(P＜0.05～P＜0.01),had significant positive relation with NIHSS(P＜0.05～P＜0.01).Men had higher serum Aβ40 levels compared with women(P＜0.05).Serum Aβ42 levels had significant positive relation with age(P＜0.01).Men had lower serum Aβ42 levels compared with women(P＜0.01).Serum Aβ42 levels had different relation with NIHSS and BI depending on the levels of serum Aβ42.When serum Aβ42 levels were within low concentration zone(22.25±9.90 pg/ml)(course of disease was 9-11d),plasma serum Aβ42 levels significant minus relation with NIHSS(P＜0.01),When serum Aβ42 levels were within high concentration zone(39.72±15.35pg/ml,39.04±14.33 pg/ml,37.75±14.56 pg/ml)(course of disease was 9-11d),plasma Aβ42 levels had significant positive relation with NIHSS and singnificant minus relation with BI(P＜0.05～P＜0.01).2.The levels of serum TC and LDL-C of post-treatment were lower than that of pretherapy in both blankgroup and statins group(P＜0.01),The levels of serum TG and LDL-C of post-treatment were also lower than that of pretherapy in statins group (P＜0.01).The levels of serum TC and LDL-C of post-treatment were lower in statins group than that in blank group(P＜0.01).The neurological functional deficit scales of 3 months later were significant different compared with that of baseline in both groups(P＜0.01),The neurological functional deficit scales of 3 months later were not significant different between blank group and statins group.Few patients had the adverse reaction of statins and the symptoms of drug adverse reaction were slight.Conclusions:1.In patients with the acute stage of cerebral infarction,serum Aβ40 levels are increased and serum Aβ42 levels are decreased.Serum Aβ40 levels have significant minus relation with serum Aβ42 levels and age.Serum Aβ42 levels have significant positive relation with age.Serum Aβ40 and serum Aβ42 levels have significant relation with sex,men have higher serum Aβ40 levels and lower serum Aβ42 levels compared with women.Serum Aβ40 and Aβ42 levels also correlate significantly with severity and outcome after ischemic stroke,higher serum Aβ40 levels,worse pathogenetic condition and worse outcome.Serum Aβ42 levels had different relation with severity and outcome of ischemic stroke depending on the levels of serum Aβ42.2.Statins have no effect on serum Aβ40 levels and Aβ42 levels.Satins can not improve the outcome of cerebral infarction.The efficacy of statins in the treatment of cerebral infarction need to be studied further.Increasing number of cases,changing in dosages and/or duration of statins given might have different results.
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