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Objective:To explore the impact of treatment duration with human urinary kallidinogenase (HUK) on the efficacy and safety of acute ischemic stroke (AIS).Methods:In this subgroup analysis of RESK study, a total of 990 AIS patients recruited from 65 centers in China between August 2015 and June 2020 were included and divided into short medication group (HUK for 8 days, n=185) or long medication group (HUK for 15 days or 21 days, n=805). The proportions of patients with modified Rankin Scale (mRS) score of 0, 0-1, 0-2 at 90 days, National Institutes of Health Stroke Scale (NIHSS) score change from baseline to 22 days, the proportions of patients with Barthel index (BI)≥95 at 90 days, and the incidences of adverse events were analyzed. Comparisons between groups were conducted using chi-square test, single factor and multivariate Logistic regression analysis, etc. Results:Multivariate regression analysis showed that the proportions of patients with 90-day mRS score of 0-2 [74.1% (137/185) vs 75.0% (604/805); OR=1.047, 95% CI 0.676-1.620, P=0.838] and 22-day NIHSS score change from baseline (4.60±2.00 vs 4.26±2.80; OR=-0.390, 95% CI -1.125-0.344, P=0.297) showed no statistically significant difference between the short medication and long medication groups; the proportions of patients with 90-day mRS score of 0-1 [48.1% (89/185) vs 59.1% (476/805); OR=0.674, 95%CI 0.463-0.983, P=0.041] and 90-day BI≥95 [43.6% (79/181) vs 55.1% (442/802); OR=0.614, 95%CI 0.420-0.897, P=0.012] were significantly lower in the short medication group than in the long medication group. There was no statistically significant difference in the incidences of adverse events between these 2 groups. Conclusions:In AIS patients, consecutive 8-day dosing of HUK improved immediate (22-day NIHSS score) and long-term outcome (90-day mRS score 0-2) and was safely tolerated. When applicable, extended duration of HUK could improve long-term disability-free rate (90-day mRS score 0-1) and quality of life (90-day BI) without increasing the risk of adverse events.
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Objective To investigate the efficacy and safety of Urinary kallidinogenase(UK)combined with butylphthalide in patients with acute cardioembolic stroke(ACS).Methods A retrospective collection was performed for ACS patients diagnosed and treated in Hangzhou First People's Hospital from May 2022 to April 2023.According to the treatment protocol,ACS patients were divided into UK group and Butylphthalide+UK group.The clinical efficacy,neurological function,serum indexes(Hcy,NT-proBNP and VEGF)and prognosis of the two groups were compared after 2 weeks of treatment.Results A total of 86 ACS patients were included in the study,including 43 in the UK group and 43 in the Butylphthalide+UK group.After treatment,the total effective rate of treatment in the Butylphthalide+UK group was significantly higher than that in the UK group(P<0.05),and there was no significant difference in the incidence of adverse reactions between the two groups(P>0.05).In addition,the expression levels of Hcy and NT-proBNP in ACS patients in the Butylphthalide+UK group were significantly lower than those in the UK group(P<0.05),while the expression levels of VEGF were significantly higher than those in the UK group(P<0.05).The NIHSS score and mRS score of ACS patients in the Butylphthalide+UK group were significantly lower than those in the UK group(P<0.05).The rate of collateral circulation establishment in the Butylphthalide+UK group was significantly higher than that in the UK group(P<0.05).Conclusion Butaphthalide combined with UK has significant efficacy and high safety in ACS patients,which may be achieved by regulating the expression levels of serum Hcy,NT-proBNP and VEGF,thereby improving neurological function and promoting the establishment of collateral circulation.
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Objective To study the protective effect of human urinary kallidinogenase (HUK) on focal cerebral ischemia-reperfusion injury in rats via phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) signaling pathway.Methods Eighty adult male SD rats were randomly divided into sham-operated group,model group,HUK group and LY294002 group (n=20).The rat focal cerebral ischemia-reperfusion models in the latter three groups were established by suture-occluded method;model group and HUK group were,respectively,injected with sterile saline or HUK 1.0 mL/kg via tail vein 3 h after reperfusion;rats in the LY294002 group accepted intraventricular injection of 10 nmol LY294002 before cerebral ischemia and caudal vein injection of 1.0 mL/kg HUK three h after reperfusion.Twenty-four h after reperfusion,Neurological Deficit Scale was performed,cerebral infarct volumes were detected by 2,3,5-triphenyltetrazolium chloride (TTC) staining,and protein expressions of Akt,phosphorylated (p)-Akt and Caspase-3 were assessed by Western blotting.Results As compared with those in the model group,the Neurological Deficit Scale scores were significantly lower,cerebral infarct volumes were significantly smaller,p-Akt expression was significantly increased,and Caspase-3 expression was significantly decreased in the HUK group (P＜0.05).As compared with those in the HUK group,Neurological Deficit Scale scores were significantly higher,infarction volumes were significantly increased,p-Akt expression was significantly decreased,and Caspase-3 expression was significantly increased in the LY294002 group (P＜0.05).Conclusion HUK has neuro-protective effect through up-regulating p-Akt expression in the PI3K/Akt signaling pathway and down-regulating Caspase-3 expression.
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Objective@#To explore the clinical benefits and risks of intravenous thrombolysis combined with urinary kallidinogenase in the treatment of minor stroke.@*Methods@#The clinical data of 86 patients with minor stroke were retrospectively analyzed. Patients who received intravenous thrombolysis combined with urinary kallidinogenase were included in observation group (n=48), and those who received intravenous thrombolysis alone were included in control group (n=38). Before treatment and after 2 weeks of treatment, the imaging blood flow perfusion parameters [cerebral blood flow (CBF), mean transit time (MTT), time to peak (TTP)], and breath holding test indexes [cerebral vascular reactivity (CVR), breath holding index (BHI)] and serum biochemical indicators [vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF)] were compared between the two groups. The occurrence of adverse drug reactions during course of treatment and rehabilitation effects at 3 months after treatment [US National Institutes of Health Stroke Scale (NIHSS), modified Rankin Scale (mRS)] were analyzed in the two groups.@*Results@#After 2 weeks of treatment, the CBF, CVR, BHI and serum levels of VEGF and bFGF in the two groups were significantly higher than those before treatment, and the indexes in observation group were significantly higher than those in control group (P<0.05). The MTT and TTP levels in the two groups were significantly higher than those before treatment, and the levels in observation group were significantly higher than those in control group (P<0.05). There was no significant difference in the incidence rate of adverse drug reactions between the two groups during course of treatment (P>0.05). At 3 months after treatment, there was no statistically significant difference in the effective rate of rehabilitation between the two groups (P>0.05), but the Mann-Whitney U rank sum test between-groups showed that the overall rehabilitation effects in observation group were significantly better than those in control group (P<0.05).@*Conclusions@#Intravenous thrombolysis has certain treatment effects in patients with minor stroke, and its safety is within the clinical controllable range. Combined with urinary kallidinogenase can obtain ideal long-term prognosis, and it is beneficial to the recovery of neurological function.
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Objective: To observe the effects of different doses of human urinary Kallidinogenase (HUK) on the expression of bradykinin 1 receptor (B1R) and bradykinin 2 receptor (B2R) in SD rats with middle cerebral artery occlusion(MCAO). Methods: The right MCAO model of SD rats was established by modified Zea Longa thread thrombus method. The 25 successfully prepared SD rats were randomly divided into five groups (5 in each group):the Sham group,the I/R model group (I/R +saline group),the HUK low dose treatment group (I/R + LDP group),the HUK medium dose treatment group (I/R + MDP group) and the HUK high dose treatment group (I/R + HDP group). After 30 min,each group was given HUK (the I/R + LDP group:3. 50 × 10-3 PNAU/kg;the I/R + MDP group:8. 75 × 10-3 PNAU/kg;the I/R + HDP group: 17.50 × 10-3 PNAU/kg) or saline tail vein injection for continuous 7 days. The samples were taken after regular injection once a day. The relative expression of mRNA in the marginal area of infarction was detected by real-time quantitative reverse transcription-polymerase chain reaction (RT-PCR),and microvascular growth density (MVD) was measured by vWF factor inimuno -fluorescence (FITC). Results (1)B1R mRNA expression;Compared with I/R + saline group, the mRNA expression of B1R in I/R + LDP group,I/R + MDP group,I/R + HDP group was all up-regulated ([0. 34 ± 0. 05], [0. 35 ± 0. 04], [0. 47 ± 0. 03] vs. [0.23 ±0.05],all P <0.05);Compared with I/R + LDP group and I/R + MDP group,the mRNA expression of B1R in I/R +HDP group was was all up-regulated (all P<0.05). (2)B2R mRiNA expression:Compared with Sham group, the mRNA expression of B2R in I/R + saline group was up-regulated([0.33 ±0.01]vs. [0.23 ± 0. 02],P <0. 05);Compared with I/R + saline group, the mRNA expression of B2R in I/R + LDP group, I/R +MDP group, I/R + HDP group was all up-regulated ([0. 49 ± 0. 02], [0. 52 ±0. 04], [0. 71 ± 0. 03], respectively,all P < 0. 05); Compared with I/R + LDP group and I/R + MDP group, the mRNA expression of B2R in I/R + HDP group was was all up-regulated (all P <0. 05). (3) Compared with Sham group, the microvessel density(MVD)in I/R + saline group was increased ([169 ±6]vs. [74 ± 12],P < 0.01);Compared with I/R + saline group,the MVD in I/R + LDP group,I/R + MDP group, I/R + HDP group was all increased([240 ±9], [252 ±9], [349 ± 17].respectively,all P<0.01);Compared with I/R + LDP group and I/R + MDP group, the MVD in I/R + HDP group was increased (all P < 0. 01). Conclusion: A certain dose of HUK could upregulate the expression of Bl R and B2R in MCAO rats to promote vascular regeneration,and the effect of high dose HUK on neovascularization was more obvious.
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Objective To explore the clinical benefits and risks of intravenous thrombolysis combined with urinary kallidinogenase in the treatment of minor stroke.Methods The clinical data of 86 patients with minor stroke were retrospectively analyzed.Patients who received intravenous thrombolysis combined with urinary kallidinogenase were included in observation group (n =48),and those who received intravenous thrombolysis alone were included in control group (n =38).Before treatment and after 2 weeks of treatment,the imaging blood flow perfusion parameters [cerebral blood flow (CBF),mean transit time (MTT),time to peak (TTP)],and breath holding test indexes [cerebral vascular reactivity (CVR),breath holding index (BHI)] and serum biochemical indicators [vascular endothelial growth factor (VEGF),basic fibroblast growth factor (bFGF)] were compared between the two groups.The occurrence of adverse drug reactions during course of treatment and rehabilitation effects at 3 months after treatment [US National Institutes of Health Stroke Scale (NIHSS),modified Rankin Scale (mRS)] were analyzed in the two groups.Results After 2 weeks of treatment,the CBF,CVR,BHI and serum levels of VEGF and bFGF in the two groups were significantly higher than those before treatment,and the indexes in observation group were significantly higher than those in control group (P ＜ 0.05).The MTT and TTP levels in the two groups were significantly higher than those before treatment,and the levels in observation group were significantly higher than those in control group (P ＜ 0.05).There was no significant difference in the incidence rate of adverse drug reactions between the two groups during course of treatment (P ＞ 0.05).At 3 months after treatment,there was no statistically significant difference in the effective rate of rehabilitation between the two groups (P ＞ 0.05),but the Mann-Whitney U rank sum test between-groups showed that the overall rehabilitation effects in observation group were significantly better than those in control group (P ＜ 0.05).Conclusions Intravenous thrombolysis has certain treatment effects in patients with minor stroke,and its safety is within the clinical controllable range.Combined with urinary kallidinogenase can obtain ideal longterm prognosis,and it is beneficial to the recovery of neurological function.
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Objective To evaluate the clinical efficacy of urinary kallidinogenase combined with sodium ozagrel on acute cerebral infarction.Methods Totally 170 cases of acute cerebral infarction were randomly and equally divided into control group and treatment group.The control group was treated with ozagrel sodium while the treatment group was given urinary kallidinogenase combined with ozagrel sodium.The clinical efficacy, HINSS score, infarct volume, blood rheology and adverse reactions of the two groups were observed.Results There was no significant difference in such general data as gender, age, site of disease and complications between the two groups (P>0.05).The efficacy of the treatment group was significantly better than that of the control group (Z=-2.28, P=0.02).The NIHSS score before and after treatment was (23.38±3.24) vs (12.22±7.17) respectively in the control group,and (23.18±2.96) vs (9.16±6.95) in the treatment group.The effect in the treatment group was better than in the control group (t=2.83,P<0.05).The infarct volume before and after treatment was (5.99±0.60) vs (5.00±0.34)respectively in control group, and(5.99+0.62) vs (4.00±0.21)in the treatment group.The effect in the treatment group was better than in the control group (t=23.11,P<0.05).Blood rheology indexes, fibrinogen, plasma viscosity, whole blood low shear viscosity and whole blood viscosity improvement in the treatment group were better than those in the control group (t=14.67,7.35,19.70和5.33,P<0.05).The two groups were not significantly different in the incidence of adverse reactions.Conclusion Yuri Klein combined with ozagrel sodium can effectively treat acute cerebral infarction by repairing the damaged neurons and improving the prognosis of patients,without obvious adverse reactions.It is worthy of clinical promotion.
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Objective To study the mechanism of urinary Kallidinogenase combined with aspirin in treat-ment of acute cerebral infarction. Methods Eighty-six patients with acute cerebral infarction were randomly divid-ed into the observation group(n=43)and the control group(n=43).The observation group was treated with uri-nary Kallidinogenase combined with aspirin,while the control group was treated only with aspirin.Two weeks after the treatment,variables of hemorheology,serum Hcy,hs-CRP,VEGF,IL-6,Cys-C,neurological deficit(NI-HSS)and daily living ability(ADL)were compared between the two groups. Results After treatment,the serum Hcy,hs-CRP,VEGF,Cys-C,IL-6 levels,the NIHSS and ADL in the observation group were significantly better improved than those of the control group(P<0.05).The clinical efficacy in the observation group was significantly higher than that of the control group[95.35%(41/43)vs 74.42%(32/43)](P<0.05).Conclusion Urinary Kal-lidinogenase combined with aspirin is more effective in the treatment of acute cerebral infarction. The mechanism may be related to the early improvements of serum Hcy,hs-CRP,VEGF,Cys-C and IL-6 expression.
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OBJECTIVE:To observe clinical efficacy of urinary kallidinogenase in the treatment of acute cerebral watershed in-farct (WSI). METHODS:128 patients with WSI were randomly divided into control group and treatment group,each of the 64 cases. Control group was given Shuxuening 15 ml added into 0.9% Sodium chloride 250 ml,ivgtt,qd;treatment group received urinary kallidinogenase 0.15 PNA added into 0.9% Sodium chloride 100 ml,ivgtt,qd. Both groups were treated for consecutive 14 days. Neurologic impairment score(NIHSS)and clinical efficacy were observed in 2 groups before treatment and 3,7 and 14 days after treatment. The blood specimens were collected after 7 and 14 days treatment,to determine serum levels of TCC. RESULTS:After treatment,NIHSS and total effective rate of treatment group were significantly higher than those of control group,with statis-tical significance(P0.05);7 days af-ter treatment,TCC level of 2 groups increased significantly,to 14 days,and a declive;the treatment group was higher than the control group,with statistical significance (P<0.05). CONCLUSIONS:Urinary kallidinogenase can improve clinical efficacy of WSI significantly,and promote neurologic impairment symptom and TCC levels.
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Objective To assess the efficacy and safety of urinary kallidinogenase combined with sodium ozagrel for cerebral infarction (CI), and provide references for clinical rational drug use. Methods Retrieved from Cochrane library, PubMed, CBM, FMJS, VIP, Wangfang database and CNKI ( published until January 2015), randomized controlled trails (RCT)about urinary kallidinogenase combined with sodium ozagrel for treatment of CI were included,then methodological quality were evaluated and statistical analysis of those studies were carried out by Rev Man 5.3.4 software. Results 19 RCTs were included,involving 1 747 patients. Results of Meta-analysis showed that urinary kallidinogenase combined with sodium ozagrel could significantly improve total effective rate[RR= 1.18, 95%CI(1.13, 1.23), Z= 7.97, P<0.000 01], cure rate[RR = 1.42, 95%CI(1.23, 1.64), Z= 4.86, P<0.000 1], neurological deficit scores[MD= -4.40, 95%CI(-5.36, -3.43), Z= 8.90,P<0. 000 01] and activity of daily living scores[MD = 19.14, 95%CI(17.39, 20.90), Z = 21.36, P<0.000 01]. Conclusion Urinary kallidinogenase combined with sodium ozagrel was effective in the treatment of CI, and no significant adverse reactions were observed. The combination therapy was worthy of clinical application.