針刺對缺血性腦損傷神經(jīng)血管單元功能的影響及機制研究
本文關鍵詞:針刺對缺血性腦損傷神經(jīng)血管單元功能的影響及機制研究 出處:《山東中醫(yī)藥大學》2013年博士論文 論文類型:學位論文
更多相關文章: 針刺 缺血性 腦損傷 神經(jīng) 血管 單元 功能 影響 機制 研究
【摘要】:隨著人口老齡化的進展,缺血性腦血管病已成為嚴重危害人類健康的疾病之一。針刺具有安全、簡便、經(jīng)濟等優(yōu)點,不僅在我國接受針灸治療的腦卒中病人有很高的比例,在國外接受針灸治療的中風患者人數(shù)亦在逐年增多,針刺療法已經(jīng)逐漸成為世界范圍內(nèi)中風的常規(guī)治療方法。 研究發(fā)現(xiàn),腦缺血的病理生理變化十分復雜,涉及到星形膠質(zhì)細胞、微血管內(nèi)皮細胞及神經(jīng)元損傷及功能失調(diào),并因此提出“神經(jīng)血管單元”的概念。為研究針刺治療中風的機制,有必要從神經(jīng)血管單元角度對其進行進一步探討,這將為其機制研究提供一個全新的思路,為其臨床的應用提供堅實的實驗基礎。 目的:電針MCAO大鼠內(nèi)關穴、曲池穴,研究針刺對星形膠質(zhì)細胞激活的影響,探討針刺調(diào)節(jié)腦微循環(huán)血流量及能量代謝的作用機制,為針刺治療缺血性腦中風的神經(jīng)血管單元機制研究提供一定的理論和實驗基礎。 方法:線栓法建立MCAO大鼠模型,通過神經(jīng)行為學評分、微循環(huán)學、組織形態(tài)學、免疫組織化學、實時定量PCR、Western blot等方法,觀察連續(xù)針刺14天對MCAO大鼠神經(jīng)功能恢復、軟腦膜微循環(huán)血流量,缺血腦組織形態(tài)改變、腦組織谷氨酸含量、膠質(zhì)纖維酸性蛋白(GFAP)、代謝性谷氨酸受體5(mGluR5)mRNA、花生四烯酸細胞色素P450表氧化酶2C11(CYP2C11)mRNA表達的影響,探討針刺通過活化星形膠質(zhì)細胞調(diào)節(jié)微血管血流量的作用及機制;通過觀察針刺對MCAO大鼠乳酸及丙酮酸含量、腦組織GFAP蛋白的表達、葡萄糖轉(zhuǎn)運體1(GLUT1)、單羧酸轉(zhuǎn)運體MCT1、單羧酸轉(zhuǎn)運體MCT2的表達的影響,從神經(jīng)血管單元功能角度探討針刺通過激活星形膠質(zhì)細胞調(diào)節(jié)腦組織微循環(huán)血流量及能量代謝的作用及機制。應用SPSS19.0統(tǒng)計學軟件進行數(shù)據(jù)統(tǒng)計及結(jié)果分析。 結(jié)果:針刺內(nèi)關穴、曲池穴能夠提高MCAO大鼠神經(jīng)體征評分,,提高腦組織中GFAP、MCT1、MCT2及GLUT1蛋白的表達;上調(diào)GFAP mRNA、mGluRs mRNA、CYP2C11mRNA的表達。針刺內(nèi)關穴、曲池穴可以有效減少MCAO大鼠腦組織中過量的谷氨酸。 結(jié)論:針刺可激活星形膠質(zhì)細胞,一方面可促進mGluRs及CYP2C11mRNA的表達,增加大鼠軟腦膜微循環(huán)血流量;另一方面,可以促進無氧糖酵解產(chǎn)物乳酸的利用,增強缺血腦組織對葡萄糖的攝取,以滿足神經(jīng)元在腦缺血時的能量需求;針刺對缺血腦組織神經(jīng)血管單元成員的功能具有調(diào)節(jié)作用,這是其治療缺血性腦中風的機制之一。
[Abstract]:With the progress of population aging, ischemic cerebrovascular disease has become one of the serious diseases endangering human health. Acupuncture is safe, simple, economic and other advantages, not only in China to receive acupuncture treatment of cerebral apoplexy patients have a high proportion in the number of people receiving foreign stroke patients with acupuncture in the acupuncture therapy also increased year by year. Has become a routine treatment in the world stroke.
The study found that the pathophysiological changes of cerebral ischemia is very complex, involving astrocytes, microvascular endothelial cells and neuronal injury and dysfunction, and therefore put forward the concept of "neurovascular unit". To study the mechanisms of acupuncture in treatment of stroke, it is necessary to carry out further discussion from the angle of neurovascular unit, which will provide a new idea for the research of its mechanism, to provide experimental foundation for the clinical application.
Objective: MCAO rats electroacupuncture Neiguan, Quchi, effect of acupuncture on the activation of astrocytes and explore the mechanism of acupuncture to regulate cerebral microcirculatory blood flow and energy metabolism, provide a theoretical and experimental foundation for the research unit mechanism of neurovascular acupuncture treatment of ischemic stroke.
Methods: the MCAO rat model was established with suture method, score, neural behavior through the microcirculation, morphology, immunohistochemistry, real-time quantitative PCR, Western blot, observed 14 days of continuous acupuncture on nerve function recovery of MCAO rats, the microcirculatory blood flow of pia mater, pathological changes of cerebral ischemia, glutamate content in brain tissue, glial fibrillary acidic protein (GFAP) and metabotropic glutamate receptor 5 (mGluR5) mRNA, four arachidonic acid cytochrome P450 oxidase 2C11 (CYP2C11) mRNA expression and the effects of acupuncture on the activation of astrocytes by regulating effect and mechanism of vascular blood flow; through the observation of acupuncture on MCAO rats of lactic acid and pyruvic acid content the expression of GFAP in brain tissue, protein, glucose transporter 1 (GLUT1), monocarboxylate transporter MCT1, monocarboxylate transporter MCT2 expression, from the perspective of neurovascular unit function by Acupuncture The role and mechanism of over activation of astrocytes in regulating microcirculation, blood flow and energy metabolism of brain tissue were analyzed by SPSS19.0 statistical software.
Results: Acupuncture Neiguan, Quchi acupoint can improve the neurological score of MCAO rats, increase GFAP and MCT1 in brain tissue, the expression of MCT2 GLUT1 protein and up regulation of GFAP mRNA, mGluRs; mRNA, CYP2C11mRNA. The expression of acupuncture Neiguan, Quchi acupoint can effectively reduce MCAO rat brain tissue in excess of glutamate.
Conclusion: acupuncture can activate astrocytes, on the one hand, can promote the expression of mGluRs and CYP2C11mRNA, increase the pial microcirculatory blood flow in rats; on the other hand, use can promote the anaerobic glycolysis of lactic acid, enhanced uptake of glucose in the brain tissue ischemia, in order to satisfy the neurons in the cerebral ischemia energy demand function; effect of acupuncture on ischemic brain neurovascular unit members has a regulatory role, it is one of the mechanisms of treating ischemic stroke.
【學位授予單位】:山東中醫(yī)藥大學
【學位級別】:博士
【學位授予年份】:2013
【分類號】:R245
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