二氢槲皮素对局灶性脑缺血损伤模型大鼠血液流变学等相关指标的影响
|
摘要
目的:观察二氢槲皮素(DHQ)对局灶性脑缺血损伤模型大鼠血液流变学等相关指标的影响。方法:将SD大鼠随机分为假手术组、模型组、尼莫地平组(阳性对照,20 mg/kg)和DHQ低、中、高剂量组(15、30、60 mg/kg),每组10只。各给药组大鼠均灌胃相应药物,假手术组大鼠灌胃等体积0.4%羧甲基纤维素钠溶液,每天1次,连续14 d。末次给药后,除假手术组外的其余各组大鼠均采用传统双侧颈总动脉结扎法复制局灶性脑缺血损伤模型。缺血24 h后,观察各组大鼠脑组织病理学变化,并检测其血液流变学指标[全血黏度(低、中、高切)、全血还原黏度(低、中、高切)、血浆黏度]、红细胞参数[红细胞压积、红细胞聚集指数(EAI)、红细胞变性指数(DI)、红细胞刚性指数(IR)]、凝血功能指标[活化部分凝血活酶时间(APTT)、凝血酶原时间(PT)、凝血酶时间(TT)、血浆纤维蛋白原(FIB)]水平。结果:与假手术组比较,模型组大鼠脑组织细胞疏松,间隙明显,缺血区周围神经元损伤明显,且全血黏度、全血还原黏度、血浆黏度、红细胞压积、EAI、IR、FIB水平均显著升高,DI、APTT、PT、TT均显著降低或缩短(P<0.05或P<0.01)。与模型组比较,各给药组大鼠上述症状均有不同程度的改善,且尼莫地平组大鼠全血黏度、血浆黏度、EAI、IR,DHQ高剂量组大鼠全血黏度、红细胞积压,DHQ各剂量组大鼠血浆黏度、EAI,DHQ中、高剂量组大鼠IR均显著降低;尼莫地平组大鼠DI、APTT、PT、TT,DHQ各剂量组大鼠DI、APTT、TT,DHQ高剂量组大鼠PT均显著升高或延长(P<0.05或P<0.01)。而其余指标组间比较,差异均无统计学意义(P>0.05)。结论:DHQ对局灶性脑缺血损伤模型大鼠具有一定的保护作用,其作用机制可能与改善其血液流变学指标以及凝血功能异常有关。
OBJECTIVE:To observe the effects of dihydroquercetin(DHQ) on hemorheology and other relevant related indexes in local cerebral ischemic injury model rats. METHODS:SD rats were randomly divided into sham operation group,model group,nimodipine group(positive control,20 mg/kg)and DHQ low-dose,medium-dose and high-dose groups(15,30,60 mg/kg),with 10 rats in each group. Administration groups were given relevant medicine intragastrically,sham operation group and model group were given constant volume of 0.4% Sodium carboxymethyl cellulose solution,once a day,for consecutive 14 d. After last administration, local cerebral ischemic injury model was induced by bilateral common carotid artery ligation in other groups except for sham operation group. After 24 h of cerebral ischemia,histopathological changes of brain tissue in rats of each group were observed; the levels of hemorheology indexes [whole blood viscosity(low, medium and high shear),whole blood reduced viscosity(low,medium and high shear),plasma viscosity],erythrocyte parameters(hematocrit,EAI,DI,IR),coagulation function indexes(APTT,PT,TT,FIB)were detected. RESULTS:Compared with sham operation group,the cells in the brain tissue of model group were loose,the gap was obvious,and the neurons around the ischemic area were damaged obviously;the levels of whole blood viscosity,whole blood reduced viscosity,plasma viscosity,hematocrit,EAI,IR and FIB were increased significantly,while the levels of DI,APTT,PT and TT were decreased or shortened significantly(P<0.05 or P<0.01). Compared with model group,above symptoms of administration groups were improved to different extents,whole blood viscosity,plasma viscosity,EAI and IR of nimodipine group,whole blood viscosity and hematocrit of DHQ high-dose group,plasma viscosity and EAI of DHQ groups,and IR of DHQ medium-dose and high-dose groups were decreased significantly;DI,APTT,PT and TT of nimodipine group,DI,APTT and TT of DHQ groups and PT of DHQ high-dose group were increased or prolonged significantly(P<0.05 or P<0.01). There was no statistical significance in other indexes among those groups(P>0.05). CONCLUSIONS:DHQ can protect against local cerebral ischemic injury model rats,the mechanism of which may be associated with improving hemorheology indexes and coagulation function disorder.
OBJECTIVE:To observe the effects of dihydroquercetin(DHQ) on hemorheology and other relevant related indexes in local cerebral ischemic injury model rats. METHODS:SD rats were randomly divided into sham operation group,model group,nimodipine group(positive control,20 mg/kg)and DHQ low-dose,medium-dose and high-dose groups(15,30,60 mg/kg),with 10 rats in each group. Administration groups were given relevant medicine intragastrically,sham operation group and model group were given constant volume of 0.4% Sodium carboxymethyl cellulose solution,once a day,for consecutive 14 d. After last administration, local cerebral ischemic injury model was induced by bilateral common carotid artery ligation in other groups except for sham operation group. After 24 h of cerebral ischemia,histopathological changes of brain tissue in rats of each group were observed; the levels of hemorheology indexes [whole blood viscosity(low, medium and high shear),whole blood reduced viscosity(low,medium and high shear),plasma viscosity],erythrocyte parameters(hematocrit,EAI,DI,IR),coagulation function indexes(APTT,PT,TT,FIB)were detected. RESULTS:Compared with sham operation group,the cells in the brain tissue of model group were loose,the gap was obvious,and the neurons around the ischemic area were damaged obviously;the levels of whole blood viscosity,whole blood reduced viscosity,plasma viscosity,hematocrit,EAI,IR and FIB were increased significantly,while the levels of DI,APTT,PT and TT were decreased or shortened significantly(P<0.05 or P<0.01). Compared with model group,above symptoms of administration groups were improved to different extents,whole blood viscosity,plasma viscosity,EAI and IR of nimodipine group,whole blood viscosity and hematocrit of DHQ high-dose group,plasma viscosity and EAI of DHQ groups,and IR of DHQ medium-dose and high-dose groups were decreased significantly;DI,APTT,PT and TT of nimodipine group,DI,APTT and TT of DHQ groups and PT of DHQ high-dose group were increased or prolonged significantly(P<0.05 or P<0.01). There was no statistical significance in other indexes among those groups(P>0.05). CONCLUSIONS:DHQ can protect against local cerebral ischemic injury model rats,the mechanism of which may be associated with improving hemorheology indexes and coagulation function disorder.
引文
[1]周皖舒,彭年春,时立新,等.贵阳地区60岁以上老年人群心脑血管疾病危险因素研究[J].贵州医科大学学报,2016,41(8):935-938.
[2]曾聪彦,胡莹,高玉桥,等.熄风通脑胶囊对局灶性脑缺血再灌注大鼠血液流变学的影响[J].中成药,2015,37(9):2037-2040.
[3]SHIKOV AN,POZHARITSKAYA ON,MIROSHNYK I,et al.Nanodispersions of taxifolin:impact of solid-state properties on dissolution behavior[J].Int J Pharm,2009,377(1/2):148-152.
[4]ZU S,YANG L,HUANG J,et al.Micronization of taxifolin by supercritical antisolvent process and evaluation of radical scavenging activity[J].Int J Mol Sci,2012,13(7):8869-8881.
[5]林溢煌,方莲花,杜冠华.心肌缺血/再灌注中RhoA的调控作用研究进展[J].中国药理学通报,2015,31(10):1336-1339.
[6]蔡华君.二氢槲皮素的抗炎抗过敏及止痒活性研究[D].长春:吉林农业大学,2015.
[7]VLADUTIA GD,MIDDLETON E JR.Effect of flavonoids on enzyme secretion and endocytosis in normal and mucolipidosisⅡfibroblasts[J].Life Sci,1986,39(8):717-726.
[8]王知斌,翟亚东,苏晓琳,等.二氢槲皮素对H2O2诱导H9c2心肌细胞损伤的保护作用[J].中医药信息,2014,31(4):16-19.
[9]IVANOV IS,SIDEHMENOVA AV,SMOL’YAKOVA VI,et al.Inhibition of adenosine diphosphate-induced platelet aggregation by alpha-lipoic acid and dihydroquercetin in vitro[J].Indian J Pharmacol,2014,46(4):430-432.
[10]韩经丹.通络化痰胶囊及其有效成分对脑缺血再灌注损伤的神经保护作用及机制研究[D].北京:北京中医药大学,2012.
[11]MAKSIMOVICH NY,DREMZA IK,TROIAN EI,et al.The correcting effects of dihydroquercetin in cerebral ischemia reperfusion injury[J].Biomed Kinm,2014,60(6):643-650.
[12]李春红,赵世珂,贾敏.舒愈膏外敷对脑缺血模型大鼠肢体功能、血流变学及脑血流量的影响[J].中华中医药学刊,2012,30(9):2089-2090.
[13]李勇,夏翠英,吕明安.胃萎汤对气虚血瘀证大鼠血液流变学指标的影响[J].安徽中医学院学报,2005,24(1):22-24.
[14]李志强.欣通胶囊对急性心肌缺血大鼠血液流变学的影响[D].哈尔滨:黑龙江中医药大学,2011.
[15]赵菲菲,蔺良才,杨馨,等.白及非多糖组分对大鼠血小板活化及血液流变学的影响[J].中成药,2017,39(2):244-249.
[16]BANERJEE A,ZHANG X,MANDA KR,et al.HIV proteins(gp120 and Tat)and methamphetamine in oxidative stress-induced damage in the brain:the potential role of the thiol antioxidant n-acetylcysteine amide[J].Free Radic Biol Med,2010,48(10):1388-1398.
[17]陈小月.对急性进展性脑梗死患者进行凝血4项检测的临床价值[J].当代医药论丛,2017,15(19):190-191.
[18]袁廷伟,孙芳玲,王晓峰,等.莫诺苷对局灶性脑缺血再灌注大鼠凝血4项的影响[J].中国康复理论与实践,2013,19(2):104-106.
[19]周敏,彭丹亚.龙生蛭胶囊联合尼莫地平治疗急性脑梗死的临床研究[J].现代药物与临床,2018,33(11):2836-2839.
[2]曾聪彦,胡莹,高玉桥,等.熄风通脑胶囊对局灶性脑缺血再灌注大鼠血液流变学的影响[J].中成药,2015,37(9):2037-2040.
[3]SHIKOV AN,POZHARITSKAYA ON,MIROSHNYK I,et al.Nanodispersions of taxifolin:impact of solid-state properties on dissolution behavior[J].Int J Pharm,2009,377(1/2):148-152.
[4]ZU S,YANG L,HUANG J,et al.Micronization of taxifolin by supercritical antisolvent process and evaluation of radical scavenging activity[J].Int J Mol Sci,2012,13(7):8869-8881.
[5]林溢煌,方莲花,杜冠华.心肌缺血/再灌注中RhoA的调控作用研究进展[J].中国药理学通报,2015,31(10):1336-1339.
[6]蔡华君.二氢槲皮素的抗炎抗过敏及止痒活性研究[D].长春:吉林农业大学,2015.
[7]VLADUTIA GD,MIDDLETON E JR.Effect of flavonoids on enzyme secretion and endocytosis in normal and mucolipidosisⅡfibroblasts[J].Life Sci,1986,39(8):717-726.
[8]王知斌,翟亚东,苏晓琳,等.二氢槲皮素对H2O2诱导H9c2心肌细胞损伤的保护作用[J].中医药信息,2014,31(4):16-19.
[9]IVANOV IS,SIDEHMENOVA AV,SMOL’YAKOVA VI,et al.Inhibition of adenosine diphosphate-induced platelet aggregation by alpha-lipoic acid and dihydroquercetin in vitro[J].Indian J Pharmacol,2014,46(4):430-432.
[10]韩经丹.通络化痰胶囊及其有效成分对脑缺血再灌注损伤的神经保护作用及机制研究[D].北京:北京中医药大学,2012.
[11]MAKSIMOVICH NY,DREMZA IK,TROIAN EI,et al.The correcting effects of dihydroquercetin in cerebral ischemia reperfusion injury[J].Biomed Kinm,2014,60(6):643-650.
[12]李春红,赵世珂,贾敏.舒愈膏外敷对脑缺血模型大鼠肢体功能、血流变学及脑血流量的影响[J].中华中医药学刊,2012,30(9):2089-2090.
[13]李勇,夏翠英,吕明安.胃萎汤对气虚血瘀证大鼠血液流变学指标的影响[J].安徽中医学院学报,2005,24(1):22-24.
[14]李志强.欣通胶囊对急性心肌缺血大鼠血液流变学的影响[D].哈尔滨:黑龙江中医药大学,2011.
[15]赵菲菲,蔺良才,杨馨,等.白及非多糖组分对大鼠血小板活化及血液流变学的影响[J].中成药,2017,39(2):244-249.
[16]BANERJEE A,ZHANG X,MANDA KR,et al.HIV proteins(gp120 and Tat)and methamphetamine in oxidative stress-induced damage in the brain:the potential role of the thiol antioxidant n-acetylcysteine amide[J].Free Radic Biol Med,2010,48(10):1388-1398.
[17]陈小月.对急性进展性脑梗死患者进行凝血4项检测的临床价值[J].当代医药论丛,2017,15(19):190-191.
[18]袁廷伟,孙芳玲,王晓峰,等.莫诺苷对局灶性脑缺血再灌注大鼠凝血4项的影响[J].中国康复理论与实践,2013,19(2):104-106.
[19]周敏,彭丹亚.龙生蛭胶囊联合尼莫地平治疗急性脑梗死的临床研究[J].现代药物与临床,2018,33(11):2836-2839.