Protective Effect Of Limb Remote Ischemic Precoriditioning On Acute Cerebral Infarction Patients And Its Mechanism

BackgroudCerebral infarction refers to cerebral blood supply disorders due to vascular lesions or hemodynamic changes,which in turn causes ischemia and hypoxia in the brain tissue of the vascular supply area.Cerebral infarction resulting in extremely high mortality and disability,resulting in a serious family and social burden.Therefore,prevention and reduction of brain tissue damage in patients with cerebral infarction has become one of the clinical concerns,especially the protection and mechanism of brain tissue in patients with acute cerebral infarction.Existing studies have found that transient ischemia of various tissues and organs(kidneys,small intestine,and extremities)can enhance the tolerance of the other tissues and organs(heart and liver)to ischemia after transient ischemia throughout the body,and can alleviate the extent of tissue damage caused by long-term ischemia.Since Przyklend first described the remote ischemic preconditioning(LRmP)in 1993.In recent years,the research on the effect and mechanism of LRIP has been increasing,which proves that LRIP is safe and effective for human body.But at present,there are many researches on the protection and mechanism of LRIP on heart and other organs.There are relatively few studies on the protection of brain tissue and stay at the level of animal experiments.Therefore,we try to use LRIP to intervene ACI patients in clinical aspects,and explore its protective effect on brain tissue,so as to reduce brain tissue damage and improve neurological function in ACI in time.provide basis and help to improve the quality of life.At present,the protective mechanism of LRIP is not clear,and there may be a variety of mediating factors and conduction pathways involved.Among them,the increased expression of serum matrix metalloproteinase-9(MMP-9)is closely related to brain necrosis and brain edema.The change of serum matrix metalloproteinase-9 level has predictive value for the prognosis of ACI patients.Brain-derived neurotrophic factor(BDNF)is a neurotrophic protein.Its elevated level can promote the survival of nerve cells,increase synaptic plasticity and neurogenesis.Both of them have clinical research value in brain tissue damage and late neurological function improvement in patients with acute cerebral infarction.Therefore,we selected MMP-9 and BDNF as two factors related to brain injury and repair to study the protective mechanism of LRJP on ACI.ObjectiveTo investigate the therapeutic effect of LRIP on ACI patients and its long term prognosis.To explore the effects of LRIP on the recurrence rate of cerebral infarction,improvement of neurological function,self-care ability and basic health status.Logistic regression analysis was used to determine whether LRIP affected the long-term prognosis of ACI.By detecting the effects of LRIP on serum levels of MMP-9 and BDNF,the protective mechanism of LRIP on ACI was preliminarily explored,which could provide ideas for the clinical application of LRIP.Methods100 Acute cerebral infarction patients were randomly divided into an LRIP group and a control group,with 50 cases in each group.Patients in the control group received standard treatment for ischemic cerebrovascular disease in the hospital.The LRIP group received limb remote ischemic preconditioning in addition to the standard treatment.After the 6-month intervention,the recurrence rate,neurological function and quality of life,and blood flow of the main brain blood supply artery were analyzed.(1)The recurrence of cerebral infarction was assessed by MRI review,and the newly discovered DWI high signal suggested recurrence.The National Institutes of Health Stroke Scale(NIHSS)score was used to assess the improvement of neural function.The reduction in NIHSS scores by ? 18%prior to intervention was defined as improved neurological function and increased NIHSS scores.Or a decrease of<18%,defined as no improvement in neurological function;(2)Using Barthel's activities of daily living(ADL)index score and 36 short-term health surveys(SF-36)Self-care ability and basic health status are assessed.(3)Transcranial Doppler(TCD)was used to enroll the MCA?AC A?PA?VA and BA were evaluated in the main brain blood supply arteries to detect the average blood flow velocity of the main large blood vessels in the brain.(4)the serum levels of MMP-9 and BDNF were measured to assess the degree of brain damage and repair and explore the protective mechanism of LRIP on ICD patients.(5)Based on the data of all patients,the recurrence of cerebral infarction was defined as dependent variable YI,and the improvement of neurological function was defined as dependent variable Y2.The aforementioned evaluation index was taken as independent variable X.The independent variable P<0.05 was selected by single factor Logistic regression analysis.The factors affecting the recurrence of cerebral infarction and the improvement of neurological function were further studied by multi-factor unconditional logistic regression analysis.(6)To evaluate the long-term efficacy of LRIP in patients with ACI,after the intervene period for 6 months,we divided the intervention group into continuous intervention group(IGI)and termination intervention group(IG2),25 in each group.25 patients were randomly selected from the original control group as a new control group(CG5 n=25).Patients in IG2 and CG continued to receive standard treatment for cerebral infarction,but did not receive LRIP intervention.In addition to standard treatment,patients with IGI received LRIP intervention.The patients were followed up for 6 months.At the end of the 12th month,the above indicators were re-evaluated to observe whether the protective effect of LRIP on acute cerebral infarction persisted.Results(1)After 6 months of intervention,the recurrence rate of cerebral infarction was lower in ICD patients who received LRIP intervention,The situation of neurological improvement was higher than the control group,the difference was statistically significant(all P<0.05).(2)Barthel ADL index score and SF-36 score:Barthel ADL index score and SF-36 score between the control group and the intervention group before the intervention.There was no significant difference(all P>0.05).After 6 months of intervention,the Barthel ADL index of the intervention group was higher than that of the control group,and also higher than that of the intervention group before intervened,the difference was statistically significant(all P<0.05).The SF-36 score of the intervention group was higher than that of the control group,and also higher than that of the intervention group before intervened.The difference was statistically significant(all P<0.05).All these suggested that the intervention group should have self-care ability and improvement of basic health.better than the control group.(3)Transcranial Doppler ultrasonography showed that there was no significant difference in the mean blood flow velocity between MCA?ACA?PA?VA and BA before the intervention(all P>0.05).After the intervention,the mean blood flow velocity of the mam blood supply artery in the above-mentioned brain of the intervention group was significantly higher than that of the control group(all P<0.05);suggesting that after the LRIP intervention,the blood flow of the corresponding main blood supply artery was increased.(4)MMP-9 and BDNF levels:Before intervention,serum MMP-9 and BDNF levels in the intervention and control groups There was no significant difference between them(all P>0.05).After intervention,the MMP-9 levels in the intervention group was reduced than the control group and also lower than the same group before intervened,the difference was statistically significant(P<0.05).The BDNF levels in the intervention group was increased than the control group and also higher than the same group before intervened,the difference was statistically significant(P<0.05),suggest that LRIP intervention might reduce serum MMP-9 levels and increase BDNF levels to protect the ACI patient.(5)Univariate logistic regression analysis showed that age,diabetes,hypertension,hyperlipidemia,smoking,NIHSS score at admission and LRIP intervention were related to the recurrence of cerebral infarction(all P<0.05).Age,diabetes,hypertension,hyperIipidemia,NIHSS score at admission and LRIP intervention were related to the improvement of neurological function(all P<0.05).The factors mentioned above(P<0.05)were selected for multivariate unconditional logistic regression analysis.Age,diabetes,hypertension,hyperhpidemia,NIHSS score at admission,LRIP intervention or not were related to recurrence of cerebral infarction and improvement of neurological function(P<0.05).LRIP intervention was the protective factor(?<0).Age,diabetes,hypertension,hyperlipidemia and NIHSS score were the risk factors(p>O).(6)After 12 months of follow-up,the evaluation indexes of IG-1,IG-2 and CG were compared in two ways.The results showed that there were significant differences between IG-1 and IG-2 in the recurrence rate of cerebral infarction,the improvement rate of neurological function,the average blood flow velocity of the main cerebral blood supply arteries(ACA,PCA,VA,BA),the SF-36 score and the level of serum BDNF(all P<0.05),and between IG-1 and CG in the recurrence of cerebral infarction.There were significant differences in the rate,improvement rate of nerve function,average blood flow velocity of mam cerebral blood supply arteries(ACA,PCA,BA),Barthel ADL index score and SF-36 score(all P<0.05).There were no significant differences in the evaluation indexes between IG-2 and CG(all P>0.05).It is speculated that the continuous intervention of LRIP is of great significance to the prognosis of ACI patients.When LRJP intervention 1s terminated,its protective effect on brain tissue may disappear.ConclusionsLRIP can effectively reduce new cerebral infarction,improve neurological function,improve quality of life,and increase cerebral arterial blood flow velocity of ACI patients,which are protective factors affecting the prognosis of ACL These changes may be related to the decrease of MMP-9 expression and the increase of BDNF expression in serum caused by LRIP.LRIP has a short time window and needs continuous intervention to be protected..