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治疗中风病(缺血性)方剂的筛选及其作用机理的实验研究
SELECTION OF THE PRESCRIPTION FOR THE APOPLEXY (ISCHEMIC APOPLEXY) AND ITS EXPERIMENTAL STUDIES ON THE ACTION AND MECHANISM
【作者】 毕明刚;
【导师】 康广盛;
【作者基本信息】 黑龙江中医药大学 , 方剂学, 2001, 博士
【摘要】 本课题针对中医方剂文献卷帙浩繁,对于系统地整理、研究某一类方剂的组方配伍规律存在着困难的现状,利用现代计算机数据库Power builder 6.0研制成中医方剂统计分析系统,在理论上研究了从东汉至今的治疗中风病九百余首方剂的组方配伍规律,同时借鉴国家攻关课题“中风病证候学与临床诊断研究”的研究成果,筛选出治疗风痰瘀血,痹阻脉络型中风病的方剂(筛选方)。在实验研究部分,采用线栓法建立大鼠大脑中动脉缺血模型,运用药理、生化、免疫组化等手段,从整体、细胞因子、神经递质、基因水平探讨筛选方对急性脑缺血损伤的治疗作用和作用机理,验证了利用数据库研究方剂组方配伍规律、进而筛选出有效方剂的可行性,实现了方剂文献研究和实验研究的有机结合。结果:筛选方具有温和、持久的降压作用;明显降低体外形成血栓的长度、湿重、干重,抑制ADP诱导的血小板聚集率的升高;显著降低急性缺血脑组织的含水量;减轻缺血后TXB2水平升高,改善血液高凝状态;抑制缺血后血液中NO、NOS、CGRP含量的下降、拮抗ET的异常升高,改善血管痉挛状态;抑制缺血后Glu、GABA的升高,减轻兴奋性毒性损伤;抑制缺血脑神经细胞的凋亡;抑制脑缺血后凋亡基因fas的过度表达,并诱导抗凋亡基因Bcl-2的表达;对急性脑缺血所引发的血糖水平升高无明显作用。结论:治疗中风病,唐宋以前,从外风论治,多用温里药、解表药、补虚药(补气、补血药);金元以后,从内风论治,则以平肝息风药、化痰药、补虚药为主;现代多从血瘀论治,活血化瘀药、平肝息风药、化痰药使用较多。筛选方对中风病(缺血性)具有较好的治疗作用。其机理可能与其减轻脑水肿、扩张脑血管、改善血液循环状态、缓解兴奋性毒性、抑制缺血半暗带细胞凋亡,调节促/抗凋亡基因表达有关。
【Abstract】 ABSTRACT In view of the difficulties in the systematic studies on the prescription compatibility rules due to the vast literatures, this paper works out a statistical analytic system for TCM prescription utilizing the computer data bank Power builder 6.0 and analyses the compatibility rules for the apoplexy in more than 900 formulae recorded from the Eastern Han Dynasty to now. Using the research of the national subject Studies of Apoplexy on Syndrome and Clinical Diagnosis for reference, the recipe is selected out (selected recipe) for the apoplexy resulted from the obstruction of collaterals due to wind, phlegm and blood stasis. In the experimental studies, the ischemic model of cerebral medium sized artery is set up in the rat with thread-bolt method. The therapeutic actions and mechanism of the selected recipe on the acute cerebral ischemia are discussed on the level of entirety, cytokine, neurotransmitter and gene, by means of pharmacology, biochemistry and immunohistochemistry. It proves feasible to study the compatibility rules of prescription making use of the data bank and then select out effective recipes. Results The actions of the selected recipe are as follows: decrease the level of the blood pressure mildly and enduringly, reduce the length, dry weight and wet weight of the external thrombosis, decrease the platelet aggregation rate induced by ADP, reduce the water content in the acute ischemic brain tissues significantly, reduce the increased level of TXB2 post ischemia and improve hypercoagulability, inhabit the decreasing of NO, NOS and CGRP, and antagonize the abnormal increasing of Er, so as to improve the vascular spasm, inhibit the increasing of GABA post ischemia and abate excitatory toxic injury, inhabit the apoptosis, inhabit the over expression of the apoptosis gene fas and induce the expression of the resisting apoptosis gene Be 1? post cerebral ischemia, no obvious action is found on the increased blood sugar level due to acute cerebral ischemia. Conclusion Before Tang and Song Dynasty, the apoplexy is treated from exopathic wind with the herbs functioned in warming the interior, inducing diaphoresis and invigorating (invigorating Qi and blood). However, after Jin and Yuan Dynasty, it is treated from endogenous wind with the herbs functioned in checking hyperactivity of the liver and relieving convulsion, resolving phlegm and tonifying. In modem times, it is treated from the blood stasis and the herbs functioned in promoting blood circulation and removing blood stasis, checking hyperactivity of the liver and relieving convulsion, resolving phlegm are commonly used. The selected recipe has a good effect on the apoplexy (ischemic apoplexy). The mechanism might be related with abating the cerebral edema, dilating the cerebrovascular, inhibiting excitatory toxicity, abating the apoptosis in the ischemic semi-dark band, regulating the expression of the promoting /resisting apoptosis gene.
【Key words】 a statistical analytic system for TCM prescription; apoplexy; selected recipe; cerebral isc {hemia; excitatory toxicity; apoptosis; fas; Bel-2;
- 【网络出版投稿人】 黑龙江中医药大学 【网络出版年期】2002年 01期
- 【分类号】R289.1
- 【下载频次】496