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基于數(shù)據(jù)挖掘的腦梗塞恢復期組方規(guī)律研究與滌痰通瘀方對急性出血性腦卒中肝損害IRAK-4的干預

發(fā)布時間:2018-11-14 17:11
【摘要】:研究目的目的一通過對中醫(yī)藥治療腦梗塞恢復期處方的用藥進行數(shù)據(jù)挖掘,分析中藥治療腦梗塞恢復期的組方規(guī)律,為臨床合理有效地遣方用藥提供一定的數(shù)據(jù)支持和參考依據(jù)。對其遣方用藥規(guī)律進行提煉濃縮,同時觀察西醫(yī)學范疇內(nèi)腦梗塞恢復期與中醫(yī)中風病之間的關(guān)聯(lián)。目的二探討滌痰通瘀方在急性出血性腦卒中大鼠肝損害的作用白細胞介素-1受體相關(guān)激酶-4(IRAK-4)活性的表達。研究方法方法一收集關(guān)于中國知網(wǎng)、萬方數(shù)據(jù)庫腦梗塞恢復期的臨床相關(guān)文獻,并借助V2.5平臺建立數(shù)據(jù)庫,應用軟件中"數(shù)據(jù)分析系統(tǒng)"模塊的配方,分析數(shù)據(jù)庫建設中涉及的處方頻率、處方規(guī)則分析和新處方分析。方法二采用健康雄性成年SD大鼠,通過酶消化法、密度梯度離心以及選擇貼壁法提取KC,隨機分為正常組,腦出血組,滌痰通瘀方組,每組分6h,12h,24h,48h 4個時相亞組,通過實時熒光定量PCR觀察肝組織IRAK-4 mRNA表達,酶聯(lián)免疫吸附試驗(ELISA)檢測培養(yǎng)上清液中TNF-α的含量。研究結(jié)果(1)臨床文獻研究最終篩選出符合標準的文獻137篇,得到處方220個。220個處方涉及中藥225味,出現(xiàn)頻次位于前十位的為川芎、當歸、地龍、水蛭、黃芪、丹參、紅花、石菖蒲、桃仁、赤芍,常用的藥物組合有"川芎,當歸"、"川芎,地龍"、"川芎,黃芪"等,核心藥物是川芎、當歸、地龍和水蛭,進而演化出核心組合16個,得到新方12個。(2)實驗研究滌痰通瘀方抑制急性出血性腦卒中大鼠肝KCs細胞IRAK-4 mRNA表達,并能明顯減輕TNF-α的含量,中藥組IRAK-4蛋白表達水平與上清液TNF-α水平呈正相關(guān)。研究結(jié)論(1)臨床文獻研究結(jié)論中國知網(wǎng)和萬方數(shù)據(jù)庫上所收錄的腦梗塞恢復期的處方中使用藥物以益氣活血通絡為主。常用方劑為解語丹、補陽還五湯、通竅活血湯等。(2)實驗研究結(jié)論IRAK-4是LPS的細胞內(nèi)信號轉(zhuǎn)導的重要調(diào)節(jié)因子;滌痰通瘀方抑制IRAK-4激酶的活性,隨之引起下游關(guān)鍵炎癥因子TNF-α的產(chǎn)生明顯減少,因此,滌痰通瘀方抑制KCs的IRAK-4的激活是減輕肝損害的重要機制之一。
[Abstract]:Objective: to analyze the rule of prescription of traditional Chinese medicine in the recovery period of cerebral infarction through the data mining of the prescription of traditional Chinese medicine in the recovery period of cerebral infarction. To provide certain data support and reference basis for clinical rational and effective prescription. At the same time, the relationship between cerebral infarction convalescence and stroke in traditional Chinese medicine was observed. Objective to investigate the effect of Ditan Tongyu recipe on liver injury in rats with acute hemorrhagic stroke and to investigate the expression of interleukin-1 receptor associated kinase-4 (IRAK-4) activity. Methods one was to collect the clinical literature about the recovery period of cerebral infarction in Chinese Zhiwang and Wanfang database, and establish the database with the help of V2.5 platform, and apply the formula of "data analysis system" module in the software. This paper analyzes the prescription frequency, prescription rules and new prescriptions involved in database construction. Methods the healthy male adult SD rats were randomly divided into normal group, intracerebral hemorrhage group, Ditan Tongyu prescription group, each group with 4 subgroups: normal group, intracerebral hemorrhage group, Ditan Tongyu prescription group, each group with enzyme digestion, density gradient centrifugation and selective adherent method, and each group was divided into 4 subgroups at 6 h, 12 h, 24 h and 48 h, respectively. The expression of IRAK-4 mRNA in liver tissue was observed by real-time fluorescence quantitative PCR and the content of TNF- 偽 in culture supernatant was detected by enzyme-linked immunosorbent assay (ELISA). Results (1) in clinical literature research, 137 articles were selected and 220 prescriptions were obtained. 225 kinds of traditional Chinese medicines were obtained. The first ten prescriptions were Rhizoma Chuanxiong, Angelica sinensis, Leech, Radix Astragali, Salvia miltiorrhiza. The common drug combinations are "Chuanxiong, Angelica sinensis", "Chuanxiong, Dilong", "Chuanxiong, Huangqi" and so on. The core drugs are Chuanxiong, Angelica, Dilong and Hirudo, and then evolved 16 core combinations. Twelve new prescriptions were obtained. (2) the experimental study showed that Ditan Tongyu decoction inhibited the expression of IRAK-4 mRNA in KCs cells of liver of rats with acute hemorrhagic stroke, and significantly reduced the content of TNF- 偽. There was a positive correlation between the expression of IRAK-4 protein and the level of TNF- 偽 in supernatant. Conclusion (1) Clinical literature conclusion the prescription of recovery period of cerebral infarction included in Chinese Zhiwang and Wanfang database is mainly used to invigorate qi and activate blood circulation to clear collaterals. The commonly used prescriptions are Jieyudan, Buyang Huanwu decoction, Tongqiao Huoxue decoction and so on. (2) Experimental study suggests that IRAK-4 is an important regulatory factor of intracellular signal transduction of LPS; Ditan Tongyu recipe inhibits the activity of IRAK-4 kinase, which causes the production of TNF- 偽, a key inflammatory factor in the downstream, which is obviously reduced. Therefore, Ditan Tongyu prescription inhibits the activation of IRAK-4 of KCs is one of the important mechanisms to alleviate liver damage.
【學位授予單位】:北京中醫(yī)藥大學
【學位級別】:碩士
【學位授予年份】:2017
【分類號】:R277.7

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