Effects Of Butylphthalide Pretreatment On Hemorrhagic Transformation After Intravenous Thrombolysis Of Rt-PA In Acute Cerebral Infarction With Time Window Of 3～4.5h

Objective:To observe the effect of butylphthalide on hemorrhagic transformation(HT)after intravenous thrombolysis of recombinant tissue plasminogen activator(rt-PA)in acute cerebral infarction(ACI)with time window of 3～4.5 h.Methods:164 patients with ACI at 3～4.5 h onset were randomly divided into control group(82 cases)and research group(82 cases).The control group received rt-PA intravenous thrombolysis and routine treatment immediately after diagnosis by imaging.The research group was added with 25 mg/100 ml butylphthalide and sodium chloride injection based on the control group,intravenous infusion immediately after diagnosis by imaging,2 times/d.Both groups received continuous treatment for 14 days.Inflammatory response indicators[tumor necrosis factor-α(TNF-α),interleukin-6(IL-6)],oxidative stress index[malondialdehyde(MDA),superoxide dismutase(SOD)]and endothelial function index[nitric oxide(NO)and endothelin-1(ET-1)],HT related index[matrix metalloproteinases-9(MMP-9)and vascular endothelial growth factor(VEGF),neuron specific enolase(NSE)and plasma cellular fibronectin(c-Fn)].Neurological impairment score(NIHSS)and modified barther index(MBI)of the two groups were measured before and 14 days after treatment.to monitor the adverse drug reactions.HT judgment refers to that that there is no intracerebral hemorrhage after the first imaging examination after ACI,and there is intracerebral hemorrhage after treatment.Results:There were no significant differences in gender,age,onset time,body mass index,blood pressure,blood lipid homocysteine,glycosylated hemoglobin,past history(stroke/TIA attack,atrial fibrillation,hypertension,hyperlipidemia,diabetes,coronary heart disease)and infarction site between the two groups(all p>0.05).After 14 days of treatment,the clinical efficacy of research group was better than the control group(Z=-1.977,p=0.048).The total effective rate of research group was higher than control group(x2=4.432,p=0.035);The incidence of HT in the research group was lower than that in the control group within 14 days of treatment,(x2 4.571,p=0.033).After 14 days of treatment,the levels of TNF-α,Il-6,MDA,ET-1,MMP-9,c-Fn,NSE and NIHSS of two groups were significantly lower than those before treatment(all p<0.01),SOD,NO,VEGF levels and MBI scores were significantly increased compared with those before treatment(all p<0.01),The improvement in the research group was more significant than that in the control group(p<0.01 or p<0.05).There was no statistically significant difference in the incidence of adverse reactions between two groups(x2=0.084,p=0.773).Conclusion:Butylphthalide combined with rt-PA intravenous thrombolysis is safe and effective in the treatment of ACI patients with onset of 3～4.5 hours,Compared with rt-PA intravenous thrombolysis alone,which can reduce the incidence of HT and improve the prognosis.Improving collateral circulation,anti-inflammatory,inhibition of oxidative stress injury,improvement of vascular endothelial function and protection blood brain barrier may be its mechanism.