Efficacy Evaluation And Mechanism Study Of Edaravone And Dexamethasone In The Prevention And Treatment Of Post-ischemic Stroke Depressio

ObjectiveTo evaluate the efficacy of edaravone dexborneol on the prevention and treatment of Post-stroke depression(PSD)by observing the effects of edaravone dexborneol on neurological function,independent living ability,depression status,depression incidence,and elements of stroke syndrome in acute ischemic stroke patients;as well as explore the mechanism of action of edaravone dexborneol on depression after acute ischemic stroke by observing the effects of edaravone dexborneol on neurological function,independent living ability,depression status,depression incidence and serum inflammation-related indexes in acute ischemic stroke patients of syndrome of phlegm-heat.MethodsA prospective,cohort study protocol with an intervention protocol and a cross-sectional study protocol were used.A total of 101 patients with acute ischemic stroke(AIS)from the Third Affiliated Hospital of Beijing University of Chinese Medicine from November 2021 to January 2023 were selected.Trial 1 was divided into the test group:58 patients treated with standardized treatment+edaravone dexborneol,and the control group:43 patients treated with standardized treatment;trial 2:patients in the test group were divided into phlegm-heat evidence group and non-phlegm-heat evidence group.According to the "Diagnostic Scale of Chinese Medicine Evidence Elements for Ischemic Stroke",both internal fire and phlegmdamp scores ≥10 were divided into phlegm-heat evidence group,and the others were divided into non-phlegm-heat evidence group.At the time of enrollment,the general baseline data of the two groups were compared.Before and 2 weeks after treatment,using the National Institutes of Health Stroke Scale(NIHSS)assessed patients’ neurological deficits and treatment effects,using the Patient Health Questionnaire-9-item scale(PHQ-9)assessed depression status,using the homocysteine(HCY)and hypersensitive C-reactive protein(HsCRP)assessed the inflammatory response of the patients,using the "Diagnostic Scale of Chinese Medicine Evidence Elements for Ischemic Stroke" assessed the stroke syndrome elements of the patients.Before,2 weeks and 12 weeks after treatment,using the modified Rankin Scale(mRS)assessed patients’ independent living ability and prognosis.Before,2 weeks,4 weeks and 12 weeks after treatment,using the Hamilton Depression Inventory(HAMD)-17 items assessed the incidence of depression;recording adverse reactions during treatment.Results1.General data:The overall distribution of gender,age,blood pressure,BMI,infarct lesion and location,recurrence,history of smoking,history of alcohol consumption,previous diseases(Hypertension,Diabetes),and underlying medications were not statistically significant(P>0.05),and the two groups of trial 1 and trial 2 were comparable.2.Degree of neurological deficits and independent living ability:the overall distribution of NIHSS scores of patients with AIS in the two groups before treatment was not statistically different;at 2 weeks of treatment,the NIHSS scores of the test group decreased more significantly compared with the control group(P<0.001).The overall effective rate in the test group(84.5%)was higher than that in the control group(60.5%),and there was a statistical difference in the effective rate between the two groups(P=0.01).At 2 weeks of treatment,the NIHSS scores of patients in the phlegm-heat group were significantly lower compared with those in the non-phlegm-heat group(P=0.02),and the total effective rate was higher in the phlegm-heat group(96.7%)compared with that in the non-phlegm-heat group(71.4%,P=0.005).At 12 weeks of treatment,the mRS scale score was significantly lower in the phlegm-heat group compared with the non-phlegm-heat group(P=0.03);the proportion of good regression of mRS score ≤2 was higher in the phlegm-heat group(82.8%)than in the non-phlegm-heat group(48.0%,P=0.007).3.Depression status:The overall mean of HAMD and PHQ-9 scale scores of the two groups were not statistically different(P>0.05)and were comparable before and at 2 weeks after treatment.The HAMD scale scores of AIS patients in the test group were lower than those of the control group at 4 and 12 weeks after treatment,and the depression status of the test group was significantly improved compared with that of the control group(4 weeks:P=0.002,12 weeks:P<0.001).At 12 weeks of treatment,the simple effect was significant in the phlegm-heat evidence group and the non-phlegm-heat evidence group(P=0.02);compared with no significant difference in HAMD scores between the two time points of the nonphlegm-heat evidence group before and after 2.4 and 12 weeks of treatment(P>0.05),the HAMD scores in the phlegm-heat evidence group decreased sequentially at 2,4 and 12 weeks after treatment(2-4 weeks:P=0.002:4-12 weeks:P=0.002;2-12 weeks:P<0.001).4.Incidence of post-stroke depression:the difference in the incidence of PSD between the two groups at 2 and 4 weeks after treatment were not statistically significant(P>0.05).and the difference in the incidence of PSD between the two groups at 12 weeks after treatment was statistically significant(control group:56.1%,test group:27.8%,P=0.005);the effect of using EDB on the incidence of PSD at 12 weeks after treatment was statistically significant(OR=0.301,P=0.006).At 12 weeks after treatment,the incidence of PSD in the phlegm-heat group(13.8%)was significantly lower(P=0.03)compared with the incidence of PSD in the non-phlegm-heat group(44.0%).5.Factors associated with post-stroke depression:NIHSS and mRS scale scores were positively associated with the occurrence of PSD 12 weeks after treatment,with each 1-point increase in NIHSS score increasing the risk of PSD 12 weeks after treatment by 0.069-fold(RR=1,069,P=0.04);each 1-point increase in mRS score increased the risk of PSD 12 weeks after treatment by 0.441-fold(RR=1.441,P=0.03).EDB reduced the risk of PSD at 12 weeks post-treatment(RR=0.336,P<0.001).6.Serum inflammatory indexes:Before treatment,patients in the phlegm-heat syndrome group had higher levels of HCY and Hs-CRP than those in the non-phlegm-heat syndrome group(HCY:P=0.009;Hs-CRP:P=0.02).Compared with before treatment,patients in the test group had lower levels of HCY and Hs-CRP at 2 weeks after treatment(HCY:P=0.007;Hs-CRP:P<0.001).The levels of HCY and Hs-CRP in the patients in the phlegm-heat syndrome group decreased at 2 weeks after treatment(HCY:P=0.004;Hs-CRP:P<0.001)compared with the levels of HCY and Hs-CRP in the patients in the non-phlegm-heat syndrome group.7.Elements of stroke symptoms:At 2 weeks after treatment,the symptoms related to internal wind,internal fire,and phlegm-dampness in the test group were significantly improved compared with those in the control group,and the overall distribution of the differences among the three elements of symptoms was statistically different(P<0.05).The most frequent elements of symptoms in the acute phase of ischemic stroke patients were internal wind,followed by internal fire,blood stasis and phlegm-damp.Conclusion(1)EDB improved the degree of neurological deficits and depression after 1 month in patients after ischemic stroke.(2)In particular,EDB improved neurological function and depression after 3 months in AIS patients with phlegm-heat syndrome,and reduced the incidence of PSD after 3 months in AIS patients with phlegm-heat syndrome.(3)The phlegm-heat syndrome in AIS patients is closely related to the levels of HCY and Hs-CRP in the inflammatory response,and EDB may reduce the levels of HCY and HsCRP by suppressing the inflammatory response,thus preventing the occurrence of PSD in patients with phlegm-heat syndrome AIS.