| Objective:Stroke has become a serious global problem.Lancet Neurology published research showed that the incidence rate of stroke standardized age decreased by 8.1%in 1990 and 2016,while China increased by 5.4%,ranking first in the world.In 2016,there were 5.5 million deaths due to stroke in the world,including 1.97 million deaths in China,accounting for more than one third.Among the surviving patients,about 3/4 of them lost their ability to work in varying degrees,and 40%of them were severely disabled.The recurrence rate of acute stroke patients in the first year was 17.7%,and the cumulative recurrence rate of 5 years was more than 30%,and the mortality rate of recurrence patients was 2.67 times of that of non-recurrence patients.Thus,stroke with high incidence rate,high disability rate and high recurrence rate has become a heavy burden on social development in China.How to prevent and improve clinical efficacy has become the focus of research.Stroke can be divided into two categories:ischemic stroke(cerebral infarction/infarction)and hemorrhagic stroke(cerebral hemorrhage).Among them,ischemic stroke accounts for 70%of all strokes,which is of great significance in prevention and treatment.In 2017,the guideline of integrated diagnosis and treatment of Chinese and Western medicine for cerebral infarction recommended that integrated treatment of Chinese and Western medicine for cerebral infarction can improve the clinical efficacy of patients with cerebral infarction.In the treatment of acute stage and recovery stage,traditional Chinese medicine is mainly used to activate blood circulation and unblock collaterals.Xuesaitong,represented by Sanqi blood activating and stasis removing drugs,can significantly increase the levels of VEGF and VEGFR in the serum of patients with cerebral infarction,and up regulate their expression.VEGF and VEGFR have a strong role in promoting angiogenesis and neuroprotection.In the acute stage of cerebral infarction,they can reduce the infarct focus,promote the neogenesis of cerebral vessels in the ischemic penumbra,and save more nerve functions.However,the exact mechanism of up regulating VEGF expression remains to be further studied and explored,which is the problem of this study and strive to solve.It is known that soluble vascular endothelial growth factor receptor-1(sFlt-1)is a glycoprotein with tyrosine kinase activity,which has no signal transduction function in VEGF pathway,but can bind with VEGF with high affinity,thus inhibiting the expression of VEGF signal and playing an anti-angiogenic role.In this study,we hypothesized that the up regulation of VEGF signal expression is related to the inactive expression of sFlt-1.The experiment will verify the hypothesis by monitoring the protein content of VEGF,VEGFR2 and sFlt-1.Methods:This project is divided into two parts:evidence-based part and experimental part.In the evidence-based part,the clinical efficacy of Xuesaitong combined with western medicine in the treatment of cerebral infarction in recent 10 years was meta analyzed.Eight databases including CNKI,Wanfang Data,VIP,China biomedical literature database,PubMed,EMBASE,the Cochrane Library and clinical trials were searched,and the inclusion criteria were formulated according to the principle of Picos.The control group received aspirin,atorvastatin and edaravone,while the experimental group received Xuesaitong on the basis of the control group.The outcome indicators were NIHSS score before and after treatment,curative effect judgment based on NIHSS score and adverse events.The quality was evaluated with Cochrane bias risk assessment tool,and the data was processed by Revman 5.3 software.In the experimental part,the experiment was carried out in vitro.The experimental cells were selected as mouse brain microvascular endothelial cells(bend.3).The physical hypoxia model was used to simulate the state of ischemia and hypoxia after cerebral infarction.After the cell model was established,Xuesaitong injection was given at a best concentration.After a period of reoxygenation,the supernatant of cell lysis was collected and Western was used.The contents of VEGF,VEGFR2 and sFlt-1 in supernatant were detected by blot.In this experiment,the normal group,the model group and the experimental group were set up to detect three kinds of proteins in the supernatant of cell lysis in three groups respectively.The gray-scale analysis was carried out by Image J software and the statistical analysis was carried out by IBM SPSS 21 software.Two independent samples of t-test were selected to compare the differences between the two groups of three proteins,and the results were discussed.Results:A total of 10 articles were included in meta-analysis.The results showed that the NIHSS scores of the experimental group and the control group after treatment were statistically significant,and the overall effect test results[MD=-2.52,95%CI(-2.76,-2.27),P<0.00001]The difference between the two groups was statistically significant when the curative effect was judged as basic recovery,significant progress and no change or deterioration.The patients were basically cured[OR=1.88,95%CI(1.40,2.53),P<0.0001],significant improvement[OR=1.68,95%CI(1.30,2.17),P<0.0001],progress[OR=0.84,95%CI(0.63,1.10),P=0.21],no change or deterioration[OR=0.26,95%CI(0.18,0.37,P<0.00001)].The change of plasma viscosity was[MD=-0.55,95%CI(-0.66,-0.43),P<0.00001].Hematocrit results were[MD=-4.34,95%CI(-4.77,-3.91),P<0.00001].There was no significant difference in the incidence of adverse events between the two groups[OR=0.80,95%CI(0.45,1.44,P=0.47)]The experimental results show that:1.After 6 hours of hypoxia,compared with the normal group at the corresponding time point,the cell viability decreased(P<0.05)at 3,6 and 12 hours of reoxygenation.With the extension of reoxygenation time,the OD value increased and the cell damage improved.2.When reoxygenated for 3h,6h and 12h,Xuesaitong injection of different concentrations had a certain inhibitory effect on nonnal cells(P<0.05).3.At 3,6,and 12 hours of reoxygenation,the cells in the experimental group treated with different concentrations of Xuesaitong could not return to the normal culture state(P<0.05),but compared with the same time of reoxygenation,it could improve the cell viability(P<0.05).When the reoxygenation time was 6h and the concentration of Xuesaitong was 100 mg/L,the difference of the percentage of cell viability between the experimental group and the model group was the largest,which could be used as the conditions for subsequent experiments.4.The expression of VEGF and VEGFR2 in the experimental group and the model group were higher than that in the normal group(P<0.05),and the increase in the experimental group was more significant than that in the model group(P<0.05).The expression of sFlt-1 in the experimental group and the model group was higher than that in the normal group(P<0.05),but the expression of sFlt-1 in the experimental group was less than that in the model group(P<0.05).Conclusion:In the aspect of evidence-based,combined application of Xuesaitong compared with simple western medicine in the treatment of cerebral infarction can improve the NIHSS score of patients after treatment,reduce the degree of nerve function defect,and the clinical treatment effect is better,and can reduce the possibility of ineffective treatment and deterioration of the disease,without significantly increasing the risk of adverse events,which provides a better treatment strategy for clinical.In terms of experiment,after oxygen glucose deprivation for 6h,the cell viability gradually recovers with the prolongation of reoxygenation time.The experimental drug Xuesaitong injection has a slight inhibition effect on normal cells,but it can promote the cells after hypoxia injury.Although it cannot reach the activity state of normal cells,it is better than the model.When the concentration of Xuesaitong is 100 mg/L and the reoxygenation time is 6h,it is the most significant.At the molecular level,the experimental drug Xuesaitong injection can promote the expression of VEGF and VEGFR2,which reflect the situation of VEGF pathway after hypoxia injury.The reason may be that the experimental drug reduces the expression of sFlt-1,the competitive protein of VEGFR2,so that the expression of VEGF pathway is more active.After knowing the effect of Xuesaitong Injection on sFlt-1 protein and VEGF pathway,it is possible to broaden the scope of its use.With the increase of the follow-up related experiments and the deepening of the findings,it may be possible to apply Xuesaitong injection or total saponins of notoginseng to the diseases closely related to sFlt-1,such as pre-eclampsia or other diseases. |
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