本文選題：芎芍膠囊 + 椎基底動脈��； 參考：《中國中醫(yī)科學院》2017年碩士論文

【摘要】：目的近年來隨著介入治療技術的發(fā)展、推廣及應用,其創(chuàng)傷小、副作用少,總體治療效果好等特點被臨床認可并被廣泛應用。椎基底動脈支架術后存在著的血栓形成、腦出血、支架置入術后再狹窄以及過度灌注等并發(fā)癥,特別是支架置入術后再狹窄(ISR)的發(fā)生,不僅發(fā)生率高,還同樣影響著腦血流動力學,從而導致缺血性腦血管病(ICVD)的發(fā)生,如短暫性腦缺血發(fā)作(TIA)、癥狀性腦梗死等疾病。芎芍膠囊作為血府逐瘀湯中的兩味主藥,具有活血化瘀的效果,經(jīng)過多年的臨床研究,能明顯降低冠狀動脈介入治療后再狹窄的發(fā)生。依從中醫(yī)“心腦同治”的原則,將芎芍膠囊運用于缺血性腦血管病-椎基底動脈支架置入術后的患者,觀察其對于預防局部血管再狹窄的療效,為治療椎基底動脈術后再狹窄探索出新的方法途徑,防止發(fā)生缺血性腦血管病。方法(1)檢索、收集相關文獻及報道,使用的檢索工具有中國學術期刊全文數(shù)據(jù)庫(CNKI)、萬方數(shù)據(jù)庫、中國生物醫(yī)學文獻數(shù)據(jù)庫(Chinese Biomedical Literature Database,CBM)、電子檢索 MEDLINE 數(shù)據(jù)庫、EMBASE 數(shù)據(jù)庫等。整理所收集數(shù)據(jù)及資料,分析椎基底動脈支架術后再狹窄的發(fā)生率、產(chǎn)生原理、相關因素及相關措施;中藥類藥物對冠狀動脈支架術后再狹窄的臨床研究,擴展至中藥類藥物對椎基底動脈支架置入術后再狹窄的預防研究。(2)制定相應的臨床研究方案、方法、流程及具體實行措施,設計“芎芍膠囊臨床觀察表格”并應用到此次課題中,將美國國立衛(wèi)生研究院卒中量表(NIHSS)及日常生活能力量表—巴氏指數(shù)(Brath指數(shù))作為神經(jīng)功能評分;同時與合作醫(yī)院(首都醫(yī)科大學宣武醫(yī)院)積極聯(lián)系及配合,共同協(xié)調(diào)完成此項臨床研究。(3)選取標準:年齡在18-80歲之間、在椎基底動脈系統(tǒng)(包括椎動脈顱內(nèi)、顱外段及基底動脈)成功接受球囊擴張和/或支架置入、術后均常規(guī)口服阿司匹林腸溶片100mgqd+氯吡格雷片75mgqd共6個月、中醫(yī)辨證分型屬于“血瘀證和/或氣虛證”的患者,預計選取80例患者。將80例經(jīng)皮椎動脈支架置入成功的缺血性腦血管病患者,通過隨機數(shù)字表的方法,為西藥常規(guī)治療加安慰劑組(對照組)、西藥常規(guī)加芎芍膠囊(中藥組)。觀察6個月后隨訪,有7例患者不符合錄入標準(自動脫落、未規(guī)律口服抗凝及抗血小板藥物、未規(guī)律口服配給藥物),最后總計73例患者入選,分別為西藥常規(guī)加安慰劑組(對照組)40例和西藥常規(guī)加芎芍膠囊(中藥組)33例。通過對血管超聲檢查(TCD)、經(jīng)顱彩色多普勒(TCCD)、DSA等檢查,了解兩組支架術后再狹窄情況及程度。(4)嚴格按照設計要求收集資料,認真核對,保證資料的真實可靠,數(shù)據(jù)應用ACCESS進行兩遍入機,進行統(tǒng)計分析,比較中藥組與對照組椎動脈支架術后再狹窄發(fā)生情況及程度、癥狀性腦梗及短暫性腦缺性發(fā)作情況、高危因素對支架術后再狹窄的影響。結果(1)通過對文獻搜索、整理及分析,發(fā)現(xiàn)以下幾個特征:①圍手術期的抗凝及抗血小板聚集治療是預防椎基底動脈ISR的主要措施,常規(guī)應用抗凝及抗血小板聚集藥物,6個月后改為阿司匹林長期口服,因為時間一旦超過6個月,發(fā)生ISR的原因主要是由血管內(nèi)膜的過度增生所致,延長波立維的口服時間對預防ISR的意義不大。②糖尿病、病變血管成角扭曲、術后殘余狹窄、長段(10mmm)的狹窄是發(fā)生椎基底動脈ISR的獨立危險因素。而高血壓病、高脂血癥、高同型半胱氨酸癥及吸煙等是ISR的高危因素。③年齡相對較小的患者更容易發(fā)生ISR,考慮是其內(nèi)膜增生能力強、增生速度更快相關;另外,相對年齡較長的患者斑塊鈣化居多,淋巴細胞浸潤少,年少的患者斑塊中纖維成分及淋巴浸潤更多。④有研究顯示,應用自膨式支架與球囊擴張支架再狹窄發(fā)生率的差異無統(tǒng)計學意義。雖然自膨式支架6個月內(nèi)易發(fā)生再狹窄,但其后期穩(wěn)定性較球囊擴張支架更好。但仍有研究顯示,徑向應力大小影響著ISR的發(fā)生,如柔韌性較好的自膨式支架會增加動脈硬化斑塊突入到支架管腔的風險,因其較大的徑向應力可促進內(nèi)膜增生導致再狹窄的發(fā)生;而球囊擴張支架恰恰相反,其相對較小的徑向應力能減少再狹窄的發(fā)生。⑤從祖國傳統(tǒng)醫(yī)學的角度來看,無論支架置入術后無論有無并發(fā)癥的出現(xiàn),此項治療都屬于外源性創(chuàng)傷,作為一種治標及損傷性的手段,雖然可以解決“標實”的問題,但是“本虛”的介入治療后依舊存在,正是這種外源性的創(chuàng)傷,加之支架置入術的過程是耗氣傷血的過程,從而導致氣虛無力推動血行,血行不暢,久而久之瘀積于脈管中,形成了術后的再狹窄,符合中醫(yī)學中“血瘀證”的范疇,治療宜活血化瘀。把中醫(yī)藥運用在椎基底動脈支架置入術后治療,不但能降低患者出現(xiàn)消化道潰瘍或者誘發(fā)出血等嚴重并發(fā)癥,還可以減少ISR的風險,縮短患者的住院時間,提高手術的成功率。⑥在芎芍膠囊干預冠心病介入治療后再狹窄的研究中,芎芍膠囊可明顯降低血漿血管緊張素Ⅱ(AngⅡ)水平,促進平滑肌細胞(SMC)凋亡,從而抑制動脈粥樣硬化(AS)的發(fā)生發(fā)展;內(nèi)膜增生、病理性血管重構協(xié)同作用可造成動脈粥樣硬化過程中管腔的缺失,膠原在病理性血管重構過程中起到了關鍵作用,芎芍膠囊可通過調(diào)節(jié)動脈粥樣硬化過程中血管壁膠原的含量改善病理性血管重構和抑制內(nèi)膜增生,起到預防管腔狹窄的作用,芎芍膠囊可明顯增強MMP-1mRNA在損傷血管部位的表達,提示芎芍膠囊預防支架后再狹窄可能與上調(diào)MMP-1mRNA的表達,增加膠原的降解,減少膠原在血管壁的沉積有關。對冠心病介入后的臨床研究也表明,芎芍膠囊可明顯降低冠狀動脈介入治療后的冠脈造影隨訪再狹窄的發(fā)生(減少45%的再狹窄),能減少心絞痛復發(fā)并有效改善患者的血瘀狀態(tài)。(2)將2012年12月到2016年6月間,在中國中醫(yī)科學院西苑醫(yī)院及首都醫(yī)科大學宣武醫(yī)院成功進行椎動脈支架置入術的患者,隨機分為西藥常規(guī)治療+安慰劑(對照組)和西藥常規(guī)+芎芍膠囊(中藥組)。其中對照組40例,男性33例,女性7例。有高血壓病史25例,糖尿病病史16例,吸煙者17例;其中置入左側椎動脈支架23個,右側椎動脈支架20個(40例患者安裝椎動脈支架43個,其中3人為左右側椎動脈支架各一個);西藥常規(guī)加芎芍膠囊(中藥組)33例,男性26例,女性7例;有高血壓病史患者27例,糖尿病病史14例,吸煙者15例;置入左側椎動脈支架17個,右側椎動脈支架18個(33例患者安裝椎動脈支架35個,其中2人為左右側椎動脈支架各一個)�；颊咴谝话闱闆r、基線方面基本相似,具有可比性。(3)入選病例73例,隨訪6個月后,芎芍膠囊中藥組的椎動脈再狹窄率為12.12%(4例/33例),對照組椎動脈狹窄率為32.5%(13例/40例),通過SPSS20.0統(tǒng)計軟件包對所收集的數(shù)據(jù)進行整合、處理及分析,首先將所有屬于計量資料的數(shù)據(jù)均用(x±S表示);其次,對全部符合納入標準的73例臨床觀察項目,進行單因素分析(計量資料的比較采用t檢驗,計數(shù)資料的比較采用卡方檢驗,以P0.05為差異具有統(tǒng)計學意義),最后比較兩組在ISR的發(fā)生率有無顯著性差異,結果顯示有顯著性差異(P0.05),具有統(tǒng)計學意義。中藥組與對照組相比較,其癥狀性腦梗及TIA的發(fā)生率無顯著性差異。(4)芎芍膠囊中藥組與對照組關于中醫(yī)辨證論治評分顯示:①治療前粗略觀察,氣虛證評分明顯低于血瘀證評分。②對兩組組內(nèi)治療前后,分別采用配對樣本t檢驗發(fā)現(xiàn),“氣虛證”評分中,治療前后均值未見明顯變化,差異無統(tǒng)計學意義(中藥組P=0.292,對照組P=0.065,兩組P0.05),說明支架置入術及術后用藥,對氣虛證患者影響不明顯;“血瘀證”評分中,兩組治療前后均值有明顯降低,其差異具有統(tǒng)計學意義(P0.05),說明支架置入術和/或用藥,均可改善血瘀癥狀。③對兩組組間采用獨立樣本t檢驗發(fā)現(xiàn),血瘀證術后中藥組與對照組均值具有差異,有統(tǒng)計學意義(P0.05),說明中藥組在術后改善狹窄率優(yōu)于對照組。結論(1)經(jīng)過6個月后的療效觀察,發(fā)現(xiàn)血管收縮、新生內(nèi)膜多度增生、血栓形成、血管重塑,最終可導致椎基底動脈支架置入術后再狹窄,其機理符合中醫(yī)學“血瘀證”范疇。對中醫(yī)辨證證型屬于“血瘀證”的患者,芎芍膠囊不僅能降低椎動脈支架置入術后局部血管再狹窄的發(fā)生起到預防作用,還能明顯改善血瘀證狀態(tài)。(2)此次中醫(yī)證候評分中,氣虛證評分總體不高,治療前后變化不大,考慮有以下兩個原因:①行椎基底動脈支架置入術的患者,考慮其本身因血管狹窄而出現(xiàn)一系列癥狀,這與血管再狹窄的部分機理相似,符合中醫(yī)學“血瘀證”范疇,造成了在病例選擇上的偏向性。②考慮此次研究病例偏少。(3)對于癥狀性腦梗及TIA的發(fā)生無明顯差異。(4)但由于時間及條件的限制,本此課題研究所選病例數(shù)偏少,在初步證實芎芍膠囊能減少椎基底動脈支架術后血管再狹窄的基礎上,應進一步擴大樣本量進行相關研究。
[Abstract]:Objective in recent years, with the development, popularization and application of interventional therapy, its characteristics of small trauma, less side effects and better overall therapeutic effect have been clinically recognized and widely used. There are complications such as thrombosis, cerebral hemorrhage, restenosis and overperfusion after stenting of vertebrobasilar artery, especially stent implantation. The incidence of post restenosis (ISR) is not only high, but also affects cerebral hemodynamics, which leads to the occurrence of ischemic cerebrovascular disease (ICVD), such as transient ischemic attack (TIA) and symptomatic cerebral infarction. Xiong Shao capsule, as the two main drug in Xuefu Zhuyu Decoction, has the effect of activating blood and removing stasis, after years of clinical research. It can obviously reduce the occurrence of restenosis after coronary artery interventional therapy. According to the principle of "heart and brain therapy", Xiong Shao capsule is applied to patients with ischemic cerebrovascular disease - vertebrobasilar artery stenting, and the effect on prevention of local restenosis is observed, and a new approach is explored for restenosis after the operation of vertebral basilar artery. Methods to prevent ischemic cerebrovascular disease. Method (1) retrieval, collection of related literature and reports, the retrieval tools used are Chinese academic journal full text database (CNKI), Wanfang database, Chinese biomedical literature database (Chinese Biomedical Literature Database, CBM), electronic retrieval MEDLINE database, EMBASE database Collect data and data, analyze the incidence of restenosis after stenting of vertebrobasilar artery, principle, related factors and related measures; the clinical study of restenosis after coronary stent implantation by traditional Chinese medicine drugs is extended to the prevention and study of restenosis after the brace of vertebrobasilar artery stenting. (2) formulate corresponding The clinical study scheme, method, process and specific implementation measures were used to design "Xiong Shao capsule clinical observation form" and apply the National Institutes of Health Stroke Scale (NIHSS) and the daily living capacity scale - the barson index (Brath index) as the neurological function score; and the cooperative hospital (Capital Medical University Declaration) (3) select the standard: age 18-80 years old, the vertebral basilar artery system (including the vertebral artery intracranial, the extracranial segment and basilar artery) successfully accepted balloon dilatation and / or stent implantation, and the routine oral administration of Aspirin Enteric-coated Tablets 100mgqd+ clopidogrel 75mgqd after the operation. 6 months, TCM syndrome differentiation type belongs to the patients with "blood stasis syndrome and / or qi deficiency syndrome", and 80 patients are expected to be selected. 80 cases of percutaneous vertebral artery stents are placed in the patients with successful ischemic cerebrovascular disease. By the method of random numbers, the routine treatment of Western Medicine plus placebo group (control group), western medicine routine plus Xiong Shao capsule (Chinese medicine group). 6 cases are observed. After month follow-up, 7 cases were not conformed to the standard of entry (auto fall off, irregular oral anticoagulant and antiplatelet drugs, irregular oral dispensing), and finally total of 73 patients were selected, 40 cases of Western medicine routine plus placebo group (control group) and 33 cases of Western medicine routine plus Xiong Shao capsule (Chinese medicine group). Through the TCD, the blood vessel ultrasound examination was carried out. Cranial color Doppler (TCCD), DSA and other examinations to understand the situation and degree of restenosis after two groups of stents. (4) collect data strictly according to the design requirements, carefully check the data, ensure the true and reliable data. The data are applied to the machine for two times, the statistical analysis is carried out, and the occurrence and process of restenosis after the vertebral artery stenting of the Chinese medicine group and the control group are compared and the process is compared. Degree, symptomatic cerebral infarction and transient ischemic attack, and the effect of high risk factors on post stent restenosis. Results (1) through literature search, sorting and analysis, the following characteristics are found: (1) anticoagulant and antiplatelet therapy in the perioperative period are the main measures to prevent ISR of vertebrobasilar artery. Anticoagulant and antiplatelet therapy are routinely applied. The drug was changed to aspirin for a long time after 6 months. As the time passed for more than 6 months, the cause of ISR was mainly caused by excessive hyperplasia of the intima of blood vessels. Prolonging the oral time of brili was not significant for preventing ISR. 2. Diabetes, the vascular distortion of the lesion, the postoperative remnant stenosis, and the stenosis of the long segment (10mmm) were vertebral ISR independent risk factors of basilar artery. Hypertension, hyperlipidemia, Hyperhomocysteine, and smoking are the high risk factors for ISR. (3) ISR is more likely to occur in patients with relatively younger age. There is no statistically significant difference in the incidence of restenosis between self expanding stents and balloon dilatation stents. Although self expanding stents are prone to restenosis in 6 months, the later stability is better than that of balloon dilatation stents. However, there are still studies showing that the diameter of the stent is better than that of balloon dilatation. The size of the stress affects the occurrence of ISR, such as a better flexible self expanding stent, which increases the risk of atherosclerotic plaques penetrating into the stent, because its larger radial stress can promote intimal hyperplasia to cause restenosis, and the balloon dilatation stent is the opposite, and its relatively small radial stress can reduce the occurrence of restenosis. From the point of view of traditional medicine of the motherland, no matter whether or not the stent implantation has complications, this treatment belongs to exogenous trauma. As a standard and damaging means, although it can solve the problem of "the standard", "this deficiency" still exists after the intervention treatment. It is this kind of exogenous trauma, plus branch. The process of stent implantation is the process of blood consumption and blood consumption, which leads to Qi deficiency to push blood, blood flow is not smooth, blood stasis is not smooth, and the blood stasis is accumulated in the pulse tube for a long time. It forms the restenosis after the operation. It is in line with the category of "blood stasis syndrome" in traditional Chinese medicine. The treatment should be used to activate blood and dissipate blood stasis. There are severe complications such as peptic ulcer or induced bleeding, which can also reduce the risk of ISR, shorten the time of hospitalization and improve the success rate of the operation. (SMC) apoptosis, thus inhibiting the occurrence and development of atherosclerosis (AS); intimal hyperplasia and pathological vascular remodeling synergy can cause the absence of the lumen in the process of atherosclerosis. Collagen plays a key role in the process of pathological vascular remodeling. Xiong Shao capsule can be used to regulate the content of collagen in the vascular wall during the process of atherosclerosis. The effect of improving pathological vascular remodeling and inhibiting intimal hyperplasia plays a role in preventing the stenosis of the lumen. Xiong Shao capsule can obviously enhance the expression of MMP-1mRNA in the injured part of blood vessel. It suggests that Xiong Shao capsule may increase the expression of MMP-1mRNA, increase the degradation of collagen and reduce the deposition of collagen in the vascular wall. The clinical study after the intervention showed that Xiong Shao capsule could obviously reduce the incidence of restenosis after coronary artery angiography after coronary intervention (45% reduction of restenosis), reduce the recurrence of angina and effectively improve the blood stasis of the patients. (2) from December 2012 to June 2016, in Xiyuan Hospital of Chinese Academy of Chinese medicine and the capital medicine The patients in Xuanwu Hospital of the University of science and universities were successfully treated with vertebral artery stenting, which were randomly divided into western medicine conventional therapy + placebo (control group) and Western medicine routine + Xiong Shao capsule (Chinese medicine group), of which 40 cases in the control group, 33 men, 7 women, 25 cases of hypertension, 16 diabetic history and 17 smokers, which were placed in the left vertebral artery stents 23. There were 20 stents on the right vertebral artery (40 cases with 43 vertebral artery stents, of which 3 were the left and right vertebral artery stents); the western medicine routine plus Xiong Shao capsule (Chinese medicine group) 33 cases, male 26 cases, 7 women, 27 patients with hypertension history, 14 cases of diabetes, 15 smokers, 17 left vertebral artery stents and right vertebral artery. There were 18 stents (33 patients with 35 vertebral artery stents, of which 2 were one of the left and right vertebral arteries). In general, the baseline was similar and comparable. (3) 73 cases were selected. After 6 months of follow-up, the restenosis rate of Xiong Shao capsule Chinese medicine group was 12.12% (4 cases /33 cases), and the control group's vertebral artery stenosis rate was 32. 5% (13 cases of /40 cases), the collected data were integrated, processed and analyzed through the SPSS20.0 statistical package. First, all the data belonging to the measured data were used (x + S). Secondly, the single factor analysis was carried out for all the 73 clinical observation items which were in conformity with the inclusion criteria. The comparison of the data was compared with t test and the comparison of counting data. With chi square test, P0.05 was statistically significant). At last, there was no significant difference in the incidence of ISR between the two groups. The results showed significant difference (P0.05). There was no significant difference in the incidence of symptomatic cerebral infarction and TIA between the Chinese medicine group and the control group. (4) Xiong Shao capsule Chinese medicine group and the control group. The score of TCM syndrome differentiation and treatment showed: (1) rough observation before treatment, the score of qi deficiency syndrome was significantly lower than that of blood stasis syndrome. (2) before and after treatment in the two groups, the paired sample t test showed that there was no significant change in the mean value of "Qi deficiency syndrome" before and after treatment (P=0.292, P=0.065 of the control group, and two groups of P). 0.05) the effect of stent implantation and postoperative medication on Qi deficiency syndrome was not obvious; in the "blood stasis syndrome" score, the mean value of the two groups before and after treatment was significantly reduced, and the difference was statistically significant (P0.05), indicating that the stent implantation and / or drug use could improve the blood stasis symptoms. (3) the blood stasis syndrome was found by independent sample t test among the two groups. The mean difference between the traditional Chinese medicine group and the control group was statistically significant (P0.05), indicating that the improvement of the stenosis rate in the Chinese medicine group was better than that of the control group. Conclusion (1) after the observation of the curative effect after 6 months, the vasoconstriction, neointimal hyperplasia, thrombosis and blood vessel restenosis can eventually lead to restenosis after the stenting of vertebral basilar artery. The mechanism conforms to the category of blood stasis syndrome of traditional Chinese medicine. Xiong Shao capsule can not only reduce the occurrence of local vascular restenosis after the stent implantation, but also obviously improve the state of blood stasis syndrome. (2) the score of qi deficiency syndrome is generally not high, and the treatment of qi deficiency syndrome is not high, and the treatment of qi deficiency syndrome is not high. There are two reasons for the following reasons: (1) a series of symptoms in the patients with vertebral basilar artery stent implantation, considering their own vascular stenosis, are similar to the mechanism of vascular restenosis, which conforms to the category of "blood stasis syndrome" in traditional Chinese medicine and causes the bias in the selection of cases. Less. (3) there is no significant difference in the occurrence of symptomatic cerebral infarction and TIA. (4) but due to the limitation of time and conditions, the number of cases selected in this study is less than that of the selected cases. On the basis of the preliminary confirmation that Xiong Shao capsule can reduce the restenosis after the stenting of vertebrobasilar artery, the sample should be further expanded to do the related research.

【學位授予單位】：中國中醫(yī)科學院
【學位級別】：碩士
【學位授予年份】：2017
【分類號】：R743

【參考文獻】

相關期刊論文 前10條

1 劉衛(wèi)紅;周明學;李思耐;任攀;劉紅旭;;腦心同治理論對臨床的指導意義[J];世界中醫(yī)藥;2017年02期

2 楊潔;王力力;凌晨;趙新宇;劉蓓蓓;周瑛華;華揚;;經(jīng)顱多普勒超聲聯(lián)合經(jīng)顱彩色多普勒超聲評價基底動脈狹窄支架置入療效及再狹窄因素的分析[J];中國腦血管病雜志;2016年04期

3 高長生;;心腦同治理論及其應用[J];中國社區(qū)醫(yī)師;2016年08期

4 王秋蘭;;腦血管支架種類及材料學特點與支架置入后的補體反應及干預[J];中國醫(yī)學工程;2016年02期

5 馬守亮;楊文明;王艷昕;吳云虎;侯志峰;蔡永亮;譚大宏;侯玉寶;;腦絡欣通對后循環(huán)缺血支架術后再狹窄預防作用研究[J];中醫(yī)藥臨床雜志;2015年10期

6 陳迪;唐仕歡;盧朋;楊洪軍;;基于數(shù)據(jù)科學的腦心同治機制研究[J];中國中藥雜志;2015年21期

7 趙濤;趙步長;賈力夫;何子龍;;“腦心同治”理論研究進展[J];中醫(yī)臨床研究;2015年27期

8 華揚;李娜;;頸動脈支架術后再狹窄危險因素及評價方法的研究進展[J];中國超聲醫(yī)學雜志;2014年12期

9 朱翠玲;衡百川;;“腦心同治”淺識[J];河南中醫(yī);2014年01期

10 趙濤;伍海勤;;深化腦心同治研究 提高臨床診療效果[J];中國中西醫(yī)結合雜志;2013年12期

，

本文編號：1894350