本文選題：炎癥反應(yīng) + 辣椒素�。� 參考：《山東師范大學(xué)》2011年碩士論文

【摘要】：膽堿能抗炎通路(cholinergic anti-inflammatory pathway,CAP)是指當(dāng)致病細(xì)菌入侵時(shí),體內(nèi)的迷走神經(jīng)及其遞質(zhì)乙酰膽堿(Acetylcholine,Ach)與免疫系統(tǒng)相互作用參與抗炎。已有的研究表明,迷走傳出神經(jīng)及其遞質(zhì)Ach參與了膽堿能抗炎通路的調(diào)控過程。黃健等通過先夾傷迷走神經(jīng)干中樞端,注射內(nèi)毒素后,發(fā)現(xiàn)迷走神經(jīng)傳出纖維放電頻率增加。Borovikova等直接電刺激內(nèi)毒素血癥大鼠的迷走神經(jīng)傳出纖維,可抑制肝臟和心臟腫瘤壞死因子-α(TNF-α)的生成,降低血清TNF-α的含量。Thomas等研究顯示,電刺激迷走神經(jīng)能夠抑制缺血再灌注損傷所導(dǎo)致的全血TNF-α升高,緩解缺血再灌注引起的休克。石德光、胡森等切斷迷走神經(jīng)則使心肌的TNF-α水平顯著升高,炎性損傷加重;電刺激切斷的迷走神經(jīng)遠(yuǎn)端能使內(nèi)毒素(LPS)血癥大鼠肺組織中TNF-α含量顯著降低,炎性病理改變減輕。以上主要通過夾傷、電刺激或切斷迷走神經(jīng)的方法來研究迷走傳出神經(jīng)對炎癥反應(yīng)的影響,但在迷走傳出神經(jīng)正常的情況下,其在炎癥反應(yīng)中放電頻率變化,無相關(guān)報(bào)道。 迷走傳出神經(jīng)及其遞質(zhì)Ach參與了抗炎反應(yīng),表明炎癥反應(yīng)中迷走傳出神經(jīng)位于迷走神經(jīng)背核(DMV)內(nèi)的節(jié)前神經(jīng)元被激活,那么,炎癥信息是如何傳遞至DMV的?通常認(rèn)為周圍免疫信息可通過兩種途徑傳達(dá)到腦,一是血液中的細(xì)胞因子通過缺乏血腦屏障的最后區(qū)(AP)入腦,由AP直接傳遞至DMV,或由AP經(jīng)孤束核(NTS)間接傳遞至DMV。二為細(xì)胞因子通過迷走傳入神經(jīng)將炎癥信息傳至NTS,由NTS傳到DMV。膽堿能抗炎通路中炎癥信號主要是通過缺乏血腦屏障的AP入腦還是通過迷走傳入神經(jīng)或兩者兼之,還不明確�！把铀鑳�(nèi)臟帶”(MVZ)含有兒茶酚胺(CA)類等多種神經(jīng)活性物質(zhì)。一系列研究表明MVZ內(nèi)CA能神經(jīng)元參與了心血管和胃腸道功能的調(diào)節(jié),如腦出血急性期延髓內(nèi)臟帶內(nèi)兒茶酚胺能神經(jīng)元有Fos蛋白表達(dá);大鼠在束縛浸水應(yīng)激狀態(tài)下DVC內(nèi)Fos/TH表達(dá)增加。而內(nèi)毒素炎癥時(shí),腦干NTS、DMV和AP內(nèi)的兒茶酚胺能神經(jīng)元是否參加了炎癥信息的傳遞、分析和整合,有關(guān)該方面的研究至今尚未見報(bào)道。因此,本文擬采用辣椒素去神經(jīng)化的方法觀察內(nèi)毒素炎癥時(shí)對迷走神經(jīng)傳出纖維放電、血清TNF-α水平及DVC內(nèi)c-Fos+TH表達(dá)的影響,以探討迷走神經(jīng)和DVC在膽堿能抗炎通路中的作用及其機(jī)制。 本研究分為三部分: 第一部分,觀察內(nèi)毒素(LPS)炎癥時(shí)大鼠迷走神經(jīng)放電、血壓、血清TNF-α水平以及DVC內(nèi)c-Fos表達(dá)情況。實(shí)驗(yàn)分兩組:LPS組和對照(CON)組,LPS組靜脈注射LPS;CON組靜脈注射等容量的生理鹽水。結(jié)果與結(jié)論:在LPS組,與LPS注射前相比迷走神經(jīng)放電頻率顯著增加,血壓降低但不顯著;LPS組與CON組相比,神經(jīng)放電頻率和血清TNF-α水平顯著升高,腦干NTS、DMV和AP的c-Fos表達(dá)均顯著增強(qiáng)。提示迷走神經(jīng)、AP和NTS參與了炎癥反應(yīng)。 第二部分,辣椒素去神經(jīng)化后再給予LPS刺激致炎,觀察大鼠迷走神經(jīng)傳出纖維放電、血壓、血清TNF-α水平的變化以及腦干DVC內(nèi)c-fos表達(dá)情況。實(shí)驗(yàn)分為兩組:辣椒素+內(nèi)毒素(CAS+LPS)組和LPS組,CAS+LPS組先以辣椒素去神經(jīng)化后再靜脈注射LPS刺激致炎;LPS組直接靜脈注射等容量的LPS。結(jié)果與結(jié)論:在CAS+LPS組,與LPS注射前相比迷走神經(jīng)傳出纖維放電頻率顯著增加,血壓升高但不明顯;CAS+LPS組與LPS組相比,血清TNF-α濃度顯著升高,腦干NTS、DMV和AP內(nèi)c-fos表達(dá)均顯著減弱。提示內(nèi)毒素炎癥時(shí),迷走傳出神經(jīng)纖維興奮增多,參入了抗炎癥作用。外周炎癥信息主要通過迷走傳入神經(jīng)傳遞至NTS,由NTS傳到DMN,部分炎癥信號可通過AP傳至DMN。 第三部分,利用Fos蛋白與酪氨酸羥化酶(TH)免疫雙標(biāo)的方法,觀察LPS炎癥時(shí)對腦干NTS、DMV和AP內(nèi)CA能神經(jīng)元活動的影響。實(shí)驗(yàn)分為兩組:LPS組和CON組,LPS組靜脈注射LPS;CON組靜脈注射生理鹽水。結(jié)果與結(jié)論:LPS組與CON組相比,LPS炎癥時(shí),NTS、DMV和AP內(nèi)TH陽性神經(jīng)元和TH+Fos雙標(biāo)陽性神經(jīng)元數(shù)目明顯增多,表明兒茶酚胺能神經(jīng)元參與了炎癥反應(yīng)。結(jié)果提示內(nèi)毒素炎癥時(shí),腦干NTS、DMV和AP內(nèi)的兒茶酚胺能神經(jīng)元可能參與了膽堿能抗炎癥通路炎癥信息的傳遞和炎癥反應(yīng)的調(diào)節(jié)過程。
[Abstract]:The cholinergic anti-inflammatory pathway (cholinergic anti-inflammatory pathway, CAP) refers to the interaction of the vagus nerve and its neurotransmitter acetylcholine (Acetylcholine, Ach) and the immune system in the body when the pathogenic bacteria invade. The research has shown that the vagal efferent nerve and its transmitter Ach participate in the regulation of the cholinergic anti-inflammatory pathway. After injecting endotoxin to the central end of the vagus nerve and injecting endotoxin, Huang Jian found that the frequency of the discharge of the vagus nerve was increased by.Borovikova and other direct electrical stimulation of the vagus nerve efferent fibers in the rats with endotoxemia, which could inhibit the formation of the liver and cardiac tumor necrosis factor - alpha (TNF- alpha) and reduce the content of TNF- alpha in serum.Thomas. The electrical stimulation of the vagus nerve can inhibit the increase of TNF- alpha in the whole blood caused by ischemia-reperfusion injury and relieve the shock caused by ischemia-reperfusion. Shi Deguang, Honson and other vagus nerves make the TNF- alpha level of the myocardium significantly increased and the inflammatory injury aggravated; the electric stimulation of the vagus nerve can make the lungs of the endotoxemia (LPS) rat lung. The content of TNF- alpha in the tissue decreased significantly and the inflammatory pathological changes were alleviated. The effects of the vagal efferent nerve on the inflammatory response were studied mainly by the method of clamp injury, electrical stimulation or vagotomy, but the frequency of discharge in the inflammatory response was changed without a related report.
The vagal efferent nerve and its transmitter Ach participate in the anti-inflammatory response, indicating that the preganglionic neurons in the dorsal nucleus of the vagus nerve are activated in the inflammatory response, then how does the inflammatory information transfer to DMV? It is generally believed that the peripheral immune information can be communicated to the brain in two ways, one is that the cytokines in the blood pass through the cell. The final region of the blood-brain barrier (AP) is transferred into the brain, from AP to DMV, or by AP via the nucleus of the solitary tract (NTS) to DMV. 2. The inflammatory information passes through the vagal afferent nerve to NTS, and from NTS to the DMV. cholinergic anti-inflammatory pathway, the inflammatory signal is mainly through the AP into the brain that lacks the blood-brain barrier or through the vagus. It is not clear that the "medullary visceral zone" (MVZ) contains a variety of neuroactive substances such as catecholamine (CA). A series of studies have shown that the CA neurons in MVZ are involved in the regulation of cardiovascular and gastrointestinal function, such as the expression of the Fos protein in the catechinamamine neurons in the visceral visceral zone of the cerebral hemorrhage, and the rats are bound and impregnated. In the state of water stress, the expression of Fos/TH in DVC increases. And when endotoxin inflammation, whether the catecholamine neurons in NTS, DMV and AP in the brain stem participate in the transmission of inflammatory information, analysis and integration, the study on this aspect has not yet been reported. Therefore, this paper intends to use capsaicin de neurochemical method to observe the endotoxin inflammation in the vagus The effects of nerve efferent fiber discharge, serum TNF- alpha level and the expression of c-Fos+TH in DVC are discussed in order to explore the role and mechanism of vagus and DVC in the cholinergic anti-inflammatory pathway.
This study is divided into three parts:
The first part was to observe the discharges of vagus nerve, blood pressure, serum TNF- alpha and c-Fos expression in DVC during LPS inflammation. The experiment was divided into two groups: LPS group and control group (CON), LPS group intravenous LPS, and CON group intravenous injection of normal saline. Results and conclusion: in LPS group, the frequency of vagus nerve discharge was compared with LPS injection. In group LPS, the frequency of nerve discharge and the level of TNF- alpha in serum were significantly higher than that in group CON, and the expression of c-Fos in NTS, DMV and AP in the brain stem was significantly enhanced. The vagus nerve, AP and NTS were involved in the inflammatory response.
The second part, after the capsaicin was denervated and then stimulated by LPS stimulation, observed the changes in the efferent fibers of the vagus nerve, the changes of blood pressure, the level of serum TNF- A and the expression of c-fos in the brain stem DVC. The experiment was divided into two groups: capsaicin + endotoxin (CAS+LPS) group and LPS group. The CAS+ LPS group first used capsaicin to neurochemical and then intravenously injected LPS stimulation LPS. results and conclusions of direct intravenous injection in LPS group: in group CAS+LPS, the frequency of the efferent fibers in the vagus nerve increased significantly, and the blood pressure increased but was not obvious before LPS injection; the serum TNF- alpha concentration in the CAS+LPS group was significantly higher than that in the LPS group, and the c-fos expression in the brain stem NTS, DMV and AP was significantly weakened. At the time, the excitability of the efferent nerve fibers increased and joined the anti inflammatory effect. The peripheral inflammatory information was transmitted to NTS mainly through the vagal afferent nerve, transmitted from NTS to DMN, and some of the inflammatory signals could be transmitted to DMN. through AP.
In the third part, the effects of Fos protein and tyrosine hydroxylase (TH) immunization were used to observe the effects of LPS inflammation on the activity of CA neurons in the brain stem NTS, DMV and AP. The experiments were divided into groups LPS and CON, LPS group intravenous LPS, CON group intravenous injection of saline. The number of TH positive neurons and TH+Fos double labeled neurons increased significantly, indicating that catecholamine neurons were involved in the inflammatory response. The results suggested that the catecholamine neurons in the brain stem NTS, DMV and AP may participate in the regulation of inflammatory response and inflammatory response in the cholinergic anti-inflammatory pathway.
【學(xué)位授予單位】：山東師范大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2011
【分類號】：R363

【引證文獻(xiàn)】

相關(guān)碩士學(xué)位論文 前1條

1 崔蓉;黃芩和黃連對急性肺損傷大鼠的保護(hù)作用及其與膽堿能抗炎通路的相關(guān)性實(shí)驗(yàn)研究[D];成都中醫(yī)藥大學(xué);2012年

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本文編號：2057819