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维药莎毕娅片对视网膜色素变性的药理作用及其个性化特征
塔吉古丽·阿不里克木
学位类型博士
导师阿吉艾克拜尔·艾萨
2016-06-03
学位授予单位中国科学院大学
学位授予地点北京
学位专业有机化学
关键词维药莎毕娅 制备工艺 质量标准 抗氧化 捕获测序
摘要

摘要视网膜色素变性(retinitis pigmentosa, RP)是视觉细胞及色素上皮细胞功能丧失为主要特征的一组慢性的,进行性的,遗传性视网膜变性疾病。属国际公认的眼科疑难病之一。以夜盲、进行性视野损害、眼底色素沉着和视网膜电图异常或无波为主要临床表现,多累及双眼。《新疆维吾尔自治区的维吾尔医医疗机构制剂标准书》里记载了治疗眼睛病的维吾尔医经典验方莎毕娅。“莎毕娅”的意思是“黑暗里的朋友(伴侣)”的意思,维吾尔医常用眼病制剂。维药莎毕娅的配方是芦荟270g,蒺藜120g,玫瑰花瓣150g,诃子肉135g,小茴香81g,薰鲁香81g,盒果藤根81g。功能与主治:清除异常黏液质,散气、清脑明目,止痛。用于夜盲症,头痛。本处方在临床以全粉后制成丸剂的形式应用。存在剂量大,味苦,服用、携带不方便等缺点。本研究我们将莎毕娅丸改剂型为片剂。本文首先探索莎毕娅的制备工艺,进而开展莎毕娅进行质量标准研究和成型工艺研究;本研究观察了莎毕娅对H2O2诱导ARPE-19(视网膜色素上皮细胞)氧化应激的的保护作用,检测莎毕娅保护H2O2诱导ARPE-19氧化应激的途径;利用Capture(目的区域捕获测序)的方法,检测视网膜色素变性患者的致病突变;观察了莎毕娅对视网膜色素变性和弱视患者视力的影响等研究。1. 莎毕娅片制备工艺研究本论文对莎毕娅片进行了制备工艺研究,对单因素和正交法,以没食子酸、出膏率为指标,采用正交实验法研究了最佳提取工艺。对小茴香进行了挥发油提取和饱和工艺研究,实验结果表明,蒺藜、玫瑰花瓣、诃子肉水为10倍,提取时间为2小时,提取次数为3次。过滤,离心除杂,减压浓缩,真空干燥,粉碎成细粉,芦荟、盒果藤根皮、薰鲁香等粉碎,加入上述药材浸膏粉,加包合物,加片剂辅料,制软材,制粒,干燥,压成片。2. 莎毕娅片质量标准的建立对莎毕娅片进行了质量标准研究。一般检查结果均符合中华人民共和国药典2015版 0101片剂项下重量差异、崩解时限、微生物限度等有关要求。莎毕娅片对芦荟、玫瑰花、小茴香进行了薄层鉴别,运用HPLC法对玫瑰花、诃子肉中没食子酸含量进行质量控制研究;3.莎毕娅对氧化应激下人视网膜色素上皮细胞的保护作用及机制研究本研究经MTT比色法检测不同浓度H2O2对细胞存活力的影响,不同浓度莎毕娅对ARPE-19细胞存活力的影响,不同浓度莎毕娅对100μmol/L H2O2诱导ARPE-19细胞存活力的影响。测定不同浓度莎毕娅对100μmol/L H2O2诱导ARPE-19细胞内丙二醛(MAD)、超氧化物歧化酶(SOD)、谷胱甘肽过氧物酶(GSH-Px)水平的影响,并与对照组比较,发现而20μmol/L,40μmol/L,80μmol/L莎毕娅预处理6h后可缓解外源100μmol/L H2O2处理18h所诱导的ARPE-19细胞内MDA的升高及 SOD、GSH-Px活力的下降。Western的方法检测莎毕娅通过提高Bcl-2,Bcl-xl蛋白的表达,降低Caspase-3的表达,总结莎毕娅经线粒体途径保护细胞氧化应激。4 利用二代测序技术对12个维吾尔族遗传性视网膜疾病患者的分子诊断利用基于NGS(第二代高通量测序技术)的Capture(目的区域捕获测序)的方法,对9个视网膜色素变性(RP),2个先天性黒蒙(LCA),1个视杆视锥细胞营养不良(CORD)的患者检测致病突变位点,发现8个的新的突变位点。本研究用莎毕娅对10个视网膜病变和12个弱视的患者进行一个月的治疗,发现治疗前和治疗后的患者视力的变化结果有显著性的差异。

其他摘要

AbstractRetinitis Pigmentosa(RP) is a slow,continusing,genetic disease that characterized by loss of function of cellula visualise and RPE,seen as difficult miscellaneous diseases,showing as night blindness,continuesing horizon damage,fundus pigmentosa,ERG abnormal. Most of time involving in pair eyes.In pharmaceutics standard book of Uyghur medical establishment ,we find Uyghur Medicine Shabiyar,It composed of aloes 270g,caltrop 120g, rose leaf 150g, myrobalan135g, Foeniculum vulgare Mill 81g,heguotenggen 81g,dongluxiang 81g.The major function of this drug is clean anormal phlegmatic temperament,exhausting anger,clear brain,stop aching.Using to night blindeness,head aching,improving eyesight。In this study we investigate about preparation technology,quality control,makingtechnology of Shabiyar.After that,investigate the oxsidative effection of Shabiyar’s to ARPE-19cell induced by H2O2,investigate the passway of Shabiyar of antioxidate,did molecular diagnosis to RD samples by using NGS based capture sequencing ,investigated the impact of UMX to the RP and amblyopia in clinic.1. Preparation technology of Shabiyar TabletShabiyar Tablet Preparation technology was as follows: it was prepared by the method of water extraction, the best extraction parameters were determined by the extraction yield and gallic acid, single factor experiments and orthogonal experiments. The Foeniculum vulgare Mill. To confirm the best inclusion processing conditions forβ- cyclodextrin inclusion compound of clove oil. then reflux extraction with water for thrice. 10 times the water of its own weight was Each time . Each reflux extraction lasted 2 hours. The fried liquid was gathered, then filtered.The extracta was obtained by vacuum concentration and drying in vacuum.The extracta been pulverized,adding into inclusion complex,Tablet accessories,been made into particles by 95% ethanol . drying, granulation, mixing, pressing piece1000tablets. The results showed that compound Shabiyar Tablet was prepared by the optimal process was up to the standard of the Chinese Pharmacopoeia(2015th edition).2. Research on quality standards of Shabiya..We have established quality standards of Shabiyar Tablet. Routine inspection was in line with the 2015 version of "Chinese Pharmacopoeia" requirement. Aloe barbadensis Miller. Or Aloe ferox Miller, Rosa rugosa Thunb and Foeniculum vulgare Millof Shabiyar Tablet were identificated by TLC. In addition, the HPLC method of determination the content of gallic acid was established.3.Protective impact of Shabiyar on the H2O2 induced ARPE-19 and it’s mechanisim Cunducting MTT experiment ,testing the reducing impact of H2O2 to cell viability,then by the same way, testing the cell viability of cell which is added different concentration of Shabiyar and indused by H2O2 And concluded the impact of Shabiyarto the H2O2 induced APRE-19cell.Secondly, by the process of SOD,MDA,GSHPx experiment, conclude the anti-oxidative impact of Shabiyaron ARPE-19 which is indused by H2O2. By doing western blot experiment , examined the CASPASE-3, BCL-2,BCL-XL on the protein level.4. NGS-based molecular diagnosis for 12Uyghur IRD disease capture sequencing experiment ,found 8 new allele which is related to the RP, and diagnosed this samples at the molecular level. Then, find the improve eye sighting function of Shabiyar by conducting experiment at clinical level to the samples of 25 RP disease and 20 amblyopia。

文献类型学位论文
条目标识符http://ir.xjipc.cas.cn/handle/365002/4592
专题资源化学研究室
作者单位中国科学院新疆理化技术研究所
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塔吉古丽·阿不里克木. 维药莎毕娅片对视网膜色素变性的药理作用及其个性化特征[D]. 北京. 中国科学院大学,2016.
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