基于病证结合模式探讨缺血性中风急性期证候演变与生物学指标表达水平的相关性
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摘要
目的通过探讨缺血性中风急性期证候与生物学指标的相关性,为完善精准辨证论治提供临床依据。方法采用ELISA法测定急性期缺血性中风病患者起病后72小时内、第7、14天热休克蛋白70(HSP70)、细胞间黏附分子1(ICAM-1)表达水平的变化,采用放免法测定相应时点促肾上腺皮质激素(ACTH)、皮质醇(COR)表达水平的变化,并动态采集四诊信息判断其证候要素,以方差齐性检验和组间比较的统计学方法进行数据分析。结果发病72小时内COR表达水平高或ACTH表达水平低的患者,痰热证持续时间长(P <0. 05);发病72小时内HSP70或ICAM-1表达水平高的患者气虚证持续时间长(P <0. 05)。结论发病72小时内COR表达水平高或ACTH表达水平低的患者,临床中医药干预时应适时延长清热化痰法的治疗时间;发病72小时内HSP70或ICAM-1表达水平高的患者气虚证持续时间长,临床中医药干预时应配合延长补气法的治疗时间。
Objective To provide clinical evidences for accurate treatment based on syndrome differentiation by exploring the correlation between the traditional Chinese medicine (TCM) syndromes and biomarkers in acute phase of ischemic stroke. Methods ELISA was used to detect the changes in the expression of heat shock protein 70 (HSP70) intercellular adhesion molecule-1 (ICAM-1) within 72 h and on the 7 thday and 14 thday following disease onset in patients in acute phase of ischemic stroke.Radioimmunoassay was used to detect the changes in the expression of ACTH and COR at the same time points; the syndrome elements were assessed based on the data dynamically collected with the Four TCM Diagnostic Techniques. Statistical analyses including homogeneity of variance test and comparison between groups were performed. Results Within 72 h of onset,those patients with higher COR expression or lower ACTH expression had longer duration of phlegm-heat syndrome with statistically significant differences; within 72 h of onset,those patients with higher HSP70 or ICAM-1 expression had longer duration of the syndrome of qi deficiency with statistically significant differences. Conclusion For those patients with higher COR expression or lower ACTH expression within 72 h of onset,therapy for clearing heat and eliminating phlegm should be extended appropriately when giving TCM intervention; For those patientswith higher SP72 or ICAM-1 expression within 72 h of onset,who would have longer duration of the syndrome of qi deficiency,and qi supplementing therapy should be extended appropriately when giving TCM intervention.
Objective To provide clinical evidences for accurate treatment based on syndrome differentiation by exploring the correlation between the traditional Chinese medicine (TCM) syndromes and biomarkers in acute phase of ischemic stroke. Methods ELISA was used to detect the changes in the expression of heat shock protein 70 (HSP70) intercellular adhesion molecule-1 (ICAM-1) within 72 h and on the 7 thday and 14 thday following disease onset in patients in acute phase of ischemic stroke.Radioimmunoassay was used to detect the changes in the expression of ACTH and COR at the same time points; the syndrome elements were assessed based on the data dynamically collected with the Four TCM Diagnostic Techniques. Statistical analyses including homogeneity of variance test and comparison between groups were performed. Results Within 72 h of onset,those patients with higher COR expression or lower ACTH expression had longer duration of phlegm-heat syndrome with statistically significant differences; within 72 h of onset,those patients with higher HSP70 or ICAM-1 expression had longer duration of the syndrome of qi deficiency with statistically significant differences. Conclusion For those patients with higher COR expression or lower ACTH expression within 72 h of onset,therapy for clearing heat and eliminating phlegm should be extended appropriately when giving TCM intervention; For those patientswith higher SP72 or ICAM-1 expression within 72 h of onset,who would have longer duration of the syndrome of qi deficiency,and qi supplementing therapy should be extended appropriately when giving TCM intervention.
引文
[1]中华医学会神经病学分会,中华医学会神经病学分会脑血管病学组.中国急性缺血性脑卒中诊治指南2014[J].中华神经科杂志,2015,61(4):246-257.
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[3]王阶,熊兴江,张兰凤.病证结合模式及临床运用探索[J].中国中西医结合杂志,2012,32(3):297-299.
[4]辛喜艳,张华,高颖.缺血性中风急性期痰热证的证候演变特点及其与神经功能缺损程度的关系[J].辽宁中医杂志,2010,37(9):1644-1646.
[5]辛喜艳,高颖,马斌,等.中风病气虚证与神经功能缺损程度及远期预后的关系研究[J].中国中西医结合杂志,2011,31(12):1627-1631.
[6]Boonen E,Vervenne H,Meersseman P,et al.Reduced cortisol metabolism during criticalillness[J].The New England Journal of Medicine,2013,368(16):1477-1488.
[7]尚合江.不同时间点测定血浆促肾上腺皮质激素和皮质醇对急性脑梗死的临床意义[J].河南医学研究,2014,23(8):19-21.
[8]茹妍妮,王燕宏,李新毅.重症脑梗死急性期病人皮质醇与蛋白质代谢的相关性研究[J].中西医结合心脑血管病杂志,2016,14(13):1465-1468.
[9]王军.急性脑梗死患者治疗血清Hcy和HPA轴激素水平检测的临床意义[C]//国际数字医学会、Digital Chinese Medicine.国际数字医学会数字中医药分会成立大会暨首届数字中医药学术交流会论文集,2016:1.
[10]蒋薇,席文立,付志新.丁苯酞联合银杏达莫治疗急性脑梗死的临床疗效及对HPA轴的调控作用[J].中国现代医药杂志,2018,20(5):57-59.
[11]关少侠,谌剑飞,丁萍.急性脑梗塞始发状态火热证与垂体-肾上腺轴激素的关系研究[J].中国中医急症,2001,10(6):338-339,314.
[12]关少侠,谌剑飞,马雅玲.急性缺血性中风始发状态风证与垂体-肾上腺轴激素的关系研究[J].放射免疫学杂志,2002,15(4):210-211.
[13]潘伊凡,王严冬,谌剑飞.急性脑梗死始发状态阴虚阳亢证与促肾上腺皮质激素的关系探讨[J].现代中西医结合杂志,2006,15(13):1788-1789.
[14]丁萍,谌剑飞,关少侠.脑梗死痰湿证与垂体-肾上腺激素水平及相关性睡眠障碍的关系探讨[J].中西医结合心脑血管病杂志,2009,7(11):1297-1298.
[15]Eroglu B,Kimbler DE,Pang J,et al.Therapeutic inducers of the HSP70/HSP110 protect mice against traumatic brain injury[J].JNeurochem,2014,130(5):626-641.
[16]Shevtsov MA,Nikolaev BP,Yakovleva LY,et al.Neurotherapeu tic activity of the recombinant heat shock protein Hsp70 in a model of focal cerebral ischemia in rats[J].Drug Des Devel Ther,2014,8:639-650.
[17]张小良,高赛红,杨迎春,等.大鼠局灶性脑缺血再灌注损伤白藜芦醇与HSP70蛋白表达的关系[J].解剖学研究,2018,40(3):185-188.
[18]李亚巍,金瑛,昌盛,等.蓝莓花色苷对大鼠脑缺血再灌注损伤的保护作用初探[J].毒理学杂志,2017,31(5):354-358.
[19]唐璐,孙塑伦,高颖,等.地黄饮子加减方对MCAO模型大鼠血浆HPA轴及脑组织HSP70表达的干预效应研究[J].环球中医药,2013,6(7):481-484.
[20]张芸,段劲峰,陈忠伦,等.急性脑梗死患者血清HSP70水平变化及意义[J].山东医药,2016,56(11):65-67.
[21]陈茁,罗大蓓,鲁旭阳,等.脑梗死中医证型与HSP70表达的相关性临床研究[J].中华中医药学刊,2016,34(1):49-53.
[22]曾晶晶,任迪,陆俊福,等.右美托咪定联合乌司他丁治疗大鼠缺血再灌注所致急性肺损伤[J].实用医学杂志,2016,32(13):2112-2115.
[23]吴相春,王少卿,唐璐,等.化痰通络汤对MCAO大鼠脑组织ICAM-1、MMP9表达的影响[J].中华中医药杂志,2014,29(9):2964-2966.
[24]王杰华,许秀秀,潘莹.瑞舒伐他汀对大鼠脑缺血再灌注ICAM-1和VCAM-1表达的抑制作用[J].免疫学杂志,2016,32(1):56-59.
[25]梁华峰,谢靖,申婧,等.次乌头碱对脑梗死大鼠神经功能与血清中t-PA,PAI-I含量水平的影响[J].中风与神经疾病杂志,2017,34(7):625-627.
[26]李春丽,扎西草,孙燕辉.丹参川芎嗪注射液对急性脑梗死老年患者血清血管细胞间黏附分子-1、细胞间黏附分子-1、内皮素-1和一氧化氮水平的影响[J].现代中西医结合杂志,2016,25(19):2088-2090.
[27]马金英.舒血宁注射液与奥扎格雷钠联合治疗对脑梗死患者血清IGF-1、HIF-1α和ICAM-1水平的影响[J].解放军预防医学杂志,2017,35(8):915-918.
[28]李柯.纳美芬对急性脑梗死疗效及IL-10、IL-18、ICAM-1、MMP-9水平影响[J].中国实用医药,2018,13(12):95-96.
[2]POWERS W J,RABINSTEIN A A,ACKERSON T,et al.2018guidelines for the early management of patients with acute ischemic stroke:a guideline for healthcare professionals from the A-merican Heart Association/American Stroke Association[J].Stroke,2018,49(3):46-110.
[3]王阶,熊兴江,张兰凤.病证结合模式及临床运用探索[J].中国中西医结合杂志,2012,32(3):297-299.
[4]辛喜艳,张华,高颖.缺血性中风急性期痰热证的证候演变特点及其与神经功能缺损程度的关系[J].辽宁中医杂志,2010,37(9):1644-1646.
[5]辛喜艳,高颖,马斌,等.中风病气虚证与神经功能缺损程度及远期预后的关系研究[J].中国中西医结合杂志,2011,31(12):1627-1631.
[6]Boonen E,Vervenne H,Meersseman P,et al.Reduced cortisol metabolism during criticalillness[J].The New England Journal of Medicine,2013,368(16):1477-1488.
[7]尚合江.不同时间点测定血浆促肾上腺皮质激素和皮质醇对急性脑梗死的临床意义[J].河南医学研究,2014,23(8):19-21.
[8]茹妍妮,王燕宏,李新毅.重症脑梗死急性期病人皮质醇与蛋白质代谢的相关性研究[J].中西医结合心脑血管病杂志,2016,14(13):1465-1468.
[9]王军.急性脑梗死患者治疗血清Hcy和HPA轴激素水平检测的临床意义[C]//国际数字医学会、Digital Chinese Medicine.国际数字医学会数字中医药分会成立大会暨首届数字中医药学术交流会论文集,2016:1.
[10]蒋薇,席文立,付志新.丁苯酞联合银杏达莫治疗急性脑梗死的临床疗效及对HPA轴的调控作用[J].中国现代医药杂志,2018,20(5):57-59.
[11]关少侠,谌剑飞,丁萍.急性脑梗塞始发状态火热证与垂体-肾上腺轴激素的关系研究[J].中国中医急症,2001,10(6):338-339,314.
[12]关少侠,谌剑飞,马雅玲.急性缺血性中风始发状态风证与垂体-肾上腺轴激素的关系研究[J].放射免疫学杂志,2002,15(4):210-211.
[13]潘伊凡,王严冬,谌剑飞.急性脑梗死始发状态阴虚阳亢证与促肾上腺皮质激素的关系探讨[J].现代中西医结合杂志,2006,15(13):1788-1789.
[14]丁萍,谌剑飞,关少侠.脑梗死痰湿证与垂体-肾上腺激素水平及相关性睡眠障碍的关系探讨[J].中西医结合心脑血管病杂志,2009,7(11):1297-1298.
[15]Eroglu B,Kimbler DE,Pang J,et al.Therapeutic inducers of the HSP70/HSP110 protect mice against traumatic brain injury[J].JNeurochem,2014,130(5):626-641.
[16]Shevtsov MA,Nikolaev BP,Yakovleva LY,et al.Neurotherapeu tic activity of the recombinant heat shock protein Hsp70 in a model of focal cerebral ischemia in rats[J].Drug Des Devel Ther,2014,8:639-650.
[17]张小良,高赛红,杨迎春,等.大鼠局灶性脑缺血再灌注损伤白藜芦醇与HSP70蛋白表达的关系[J].解剖学研究,2018,40(3):185-188.
[18]李亚巍,金瑛,昌盛,等.蓝莓花色苷对大鼠脑缺血再灌注损伤的保护作用初探[J].毒理学杂志,2017,31(5):354-358.
[19]唐璐,孙塑伦,高颖,等.地黄饮子加减方对MCAO模型大鼠血浆HPA轴及脑组织HSP70表达的干预效应研究[J].环球中医药,2013,6(7):481-484.
[20]张芸,段劲峰,陈忠伦,等.急性脑梗死患者血清HSP70水平变化及意义[J].山东医药,2016,56(11):65-67.
[21]陈茁,罗大蓓,鲁旭阳,等.脑梗死中医证型与HSP70表达的相关性临床研究[J].中华中医药学刊,2016,34(1):49-53.
[22]曾晶晶,任迪,陆俊福,等.右美托咪定联合乌司他丁治疗大鼠缺血再灌注所致急性肺损伤[J].实用医学杂志,2016,32(13):2112-2115.
[23]吴相春,王少卿,唐璐,等.化痰通络汤对MCAO大鼠脑组织ICAM-1、MMP9表达的影响[J].中华中医药杂志,2014,29(9):2964-2966.
[24]王杰华,许秀秀,潘莹.瑞舒伐他汀对大鼠脑缺血再灌注ICAM-1和VCAM-1表达的抑制作用[J].免疫学杂志,2016,32(1):56-59.
[25]梁华峰,谢靖,申婧,等.次乌头碱对脑梗死大鼠神经功能与血清中t-PA,PAI-I含量水平的影响[J].中风与神经疾病杂志,2017,34(7):625-627.
[26]李春丽,扎西草,孙燕辉.丹参川芎嗪注射液对急性脑梗死老年患者血清血管细胞间黏附分子-1、细胞间黏附分子-1、内皮素-1和一氧化氮水平的影响[J].现代中西医结合杂志,2016,25(19):2088-2090.
[27]马金英.舒血宁注射液与奥扎格雷钠联合治疗对脑梗死患者血清IGF-1、HIF-1α和ICAM-1水平的影响[J].解放军预防医学杂志,2017,35(8):915-918.
[28]李柯.纳美芬对急性脑梗死疗效及IL-10、IL-18、ICAM-1、MMP-9水平影响[J].中国实用医药,2018,13(12):95-96.