【摘要】：目的： 1.探討二氧化硫(sulfur dioxide, SO2)在麻醉大鼠孤束核(nucleus tractus solitarii, NTS)及頭端延髓腹外側(cè)區(qū)(rostral ventrolateral medulla, RVLM)的心血管效應(yīng)及其機(jī)制 2.探討內(nèi)源性SO2在膿毒癥大鼠肝、腎、心、腦及血清中的分布與水平變化。 3.探討SO2對(duì)膿毒癥大鼠動(dòng)脈壓力反射(areterial baroreflex, ABR)功能的影響及其機(jī)制。 方法： 1.SO2在NTS和RVLM產(chǎn)生的心血管效應(yīng)：成年雄性Spargue-Dawley (SD)大鼠50只,其中25只大鼠在NTS單側(cè)微量注射不同劑量SO2(2,20,200pmol)或人工腦脊液(artificial cerebrospinal fluid, aCSF),觀察在NTS內(nèi)注射SO2對(duì)大鼠血壓和心率產(chǎn)生的影響。余25只大鼠在RVLM單側(cè)微量注射不同劑量SO2(2,20,200pmol)或aCSF,觀察在RVLM內(nèi)注射SO2對(duì)大鼠血壓和心率產(chǎn)生的影響。 2.SO2在RVLM產(chǎn)生心血管效應(yīng)的機(jī)制：成年雄性SD大鼠43只,其中11只大鼠預(yù)先在RVLM注射aCSF或谷氨酸(Glu)促離子型受體非選擇性拮抗劑犬尿喹啉酸(KYN,15nmol)觀察其對(duì)二氧化硫在RVLM引起心血管效應(yīng)的影響。32只大鼠預(yù)先在RVLM注射aCSF、ATP敏感性鉀通道(KATP)阻斷劑格列苯脲(Gli,40μmol)、L-型鈣離子通道阻斷劑尼卡地平(Nic,200pmol)、非選擇性一氧化氮合酶(NOS)抑制劑NG硝基L精氨酸甲酯(L-NAME,15nmol)、選擇性可溶性鳥苷酸環(huán)化酶(sGC)抑制劑1H-[1,2,4]E二唑[4,3-α]喹喔啉-1-酮(ODQ,250pmol),探討RVLM內(nèi)二氧化硫的離子通道及信號(hào)轉(zhuǎn)導(dǎo)通路。 3.SO2在各組織及血清中的分布水平：用盲腸結(jié)扎穿刺(cecal ligation and puncture, CLP)法制作膿毒癥大鼠模型。采用隨機(jī)數(shù)表法將40只成年雄性SD大鼠,隨機(jī)分為假手術(shù)組(n=8)和膿毒癥模型組(n=32)。造模后3h、6h、12h及24h處死大鼠,取肝、腎、心、腦組織,并留取血清標(biāo)本。采用酶聯(lián)免疫吸附試驗(yàn)(ELISA)測(cè)定S02水平。 4.SO2對(duì)膿毒癥大鼠ABR的影響：雄。性SD大鼠66只采用隨機(jī)數(shù)表法隨機(jī)分為11組：①假手術(shù)(SO)+生理鹽水(Saline)+靜脈注射(iv)組;②CLP+Saline+iv組;③SO+SO2+iv組;④CLP+SO2+iv組;⑤SO+aCSF+NTS組;⑥SO+SO2+NTS組;⑦CLP+aCSF+NTS組；⑧CLP+SO2+NTS組;⑨CLP+KYN+NTS組;⑩SO+aCSF+SO2+NTS組(預(yù)先雙側(cè)NTS注射aCSF,而后再在同一部位注射SO2)11SO+KYN+SO2+NTS組(預(yù)先在雙側(cè)NTS注射KYN,而后再在同一部位注射SO2)。分別在給藥前、給藥后5min和30min3個(gè)時(shí)間點(diǎn)測(cè)定大鼠ABR功能。 結(jié)果： 1.SO2在NTS和RVLM產(chǎn)生的心血管效應(yīng)：NTS單側(cè)微量注射SO2產(chǎn)生劑量依賴性降低血壓和減慢心率的作用(P＜0.05)。RVLM單側(cè)微量注射SO2產(chǎn)生劑量依賴性的升高血壓和加快心率的作用(P＜0.05)。 2.SO2在RVLM產(chǎn)生心血管效應(yīng)的機(jī)制：預(yù)先RVLM注射KYN能部分阻斷SO2(20pmol)在RVLM引起的心血管效應(yīng)(P＜0.05)。預(yù)先RVLM注射Gli、 Nic、 L-NAME或ODQ能有效阻斷SO2(20pmol)在RVLM產(chǎn)生的升高血壓、加快心率的效應(yīng)(P＜0.05)。 3.SO2在各組織及血清中的分布水平：假手術(shù)組大鼠肝、腎、心臟、腦及血清中均含有一定量SO2,且以心臟組織中的含量最高。與假手術(shù)組比較,CLP造模后3h后大鼠肝、腎、心、腦及血清中SO2水平開始升高,12h有統(tǒng)計(jì)學(xué)意義,24h達(dá)到高水平。 4.SO2對(duì)膿毒癥大鼠ABR的影響：①同一組內(nèi)不同時(shí)相ABR值變化結(jié)果：與給藥前相比,SO+SO2+iv組,CLP+SO2+iv組,SO+SO2+NTS組,CLP+SO2+NTS組,SO+aCSF+SO2+NTS組給藥后5min和30min ABR值均明顯降低(P＜0.05),而CLP+KYN+NTS組明顯升高(P＜0.05)。②相同時(shí)相不同組間ABR值變化結(jié)果：給藥前,CLP+Saline+iv組明顯低于SO+Saline+iv組或SO+SO2+iv組(P0.05), CLP+aCSF+NTS組明顯低于SO+aCSF+NTS組或SO+SO2+NTS組(P＜0.05)。給藥后5min和30min, CLP+SO2+iv組明顯低于CLP+Saline+iv組(P＜0.05)或SO+Saline+iv組(P0.05), CLP+SO2+NTS組明顯低于CLP+aCSF+NTS組(P＜0.05)或SO+aCSF+NTS組(P005), CLP+KYN+NTS組明顯高于CLP+aCSF+NTS組(P＜0.05),SO+KYN+SO2+NTS組明顯高于SO+aCSF+SO2+NTS組(P＜0.05)。 結(jié)論： 1.SO2在NTS能夠引起劑量依賴性降低血壓和減慢心率的作用。SO2在RVLM能夠引起劑量依賴性升高血壓和加快心率的作用。 2.SO2可能通過激動(dòng)部分RVLM內(nèi)Glu受體參與中樞血壓的調(diào)控,該機(jī)制可能與KATP和L-型鈣通道開放有關(guān)。SO2在RVLM產(chǎn)生的升高血壓、加快心率的效應(yīng)主要與NO/cGMP信號(hào)轉(zhuǎn)導(dǎo)通路有關(guān)。 3.SO2可在正常大鼠體內(nèi)內(nèi)源性產(chǎn)生,心臟組織中的SO2水平高于其他組織；CLP大鼠體內(nèi)SO2水平高于正常，，可能參與膿毒癥大鼠的發(fā)病機(jī)制。 4.體內(nèi)8O2生成增加對(duì)膿毒癥大鼠ABR功能有降低作用,該作用不僅通過外周靜脈系統(tǒng)發(fā)揮作用,而且可能通過中樞NTS影響ABR功能；SO2對(duì)大鼠ABR功能的調(diào)節(jié),可能與Glu促離子型受體激動(dòng)有關(guān)。
[Abstract]:Purpose: 1. To study the cardiovascular effects of sulfur dioxide (SO _ 2) in the nucleus of the solitary tract (NTS) and the lateral medulla (RVLM) of the head-end of the anesthetized rats. Mechanism 2. To investigate the effect of endogenous SO2 in the liver of sepsis rats. The distribution and water of kidney, heart, brain and serum 3. To investigate the effect of SO2 on the function of arterial baroreflex (ABR) in septic rats in response to and Methods:1. The cardiovascular effects of SO2 in NTS and RVLM:50 of adult male Sprague-Dawley (SD) rats,25 of which were injected with different doses of SO2 (2,20,200 pmol) or artificial cerebrospinal fluid (aCSF) at one side of the NTS. The effects of pressure and heart rate on rat blood were observed in 25 rats at different dose of SO2 (2,20,200 pmol) or aCSF at one side of the RVLM. The effect of the pressure and heart rate.2. The mechanism of the effect of SO2 on the production of cardiovascular effects in the RVLM:43 adult male SD rats,11 of which were pre-injected with aCSF or glutamate (Glu) non-selective receptor in the RVLM. The effect of anti-agent (KYN, 15nmol) on the cardiovascular effects of sulfur dioxide on the RVLM was observed.32 rats were pre-injected with aCSF, ATP-sensitive potassium channel (KATP) blocking agent gliclazide (Gli,40. mu.mol), L-type calcium channel blocker nicardipine (N (c,200 pmol), non-selective nitric oxide synthase (NOS) inhibitor NG-nitro L-arginine methyl ester (L-NAME,15 nmol), selective soluble ornithine-acid cyclase (sGC) inhibitor 1H-[1,2,4] E dicyandiamide[4,3-1]-1-one-one (O DQ,250 pmol), and the content of sulfur dioxide in the RVLM was investigated. Ion channel and signal transduction pathway.3. Distribution of SO2 in the tissues and serum: Cecal ligation and puncture, C 40 adult male SD rats were randomly divided into the sham operation group (n = 8) using the random number table method. And the rats were sacrificed at 3 h,6 h,12 h and 24 h after the model, and the liver and kidney were taken. Serum samples were taken from the heart and brain tissue. Enzyme-linked immunosorbent assay (ELISA) was used ( ELISA) Determination of S02 level.4. The effects of 2 on the ABR in septic rats were: the male and sexual SD rats were randomly divided into 11 groups using the random number table method: sham operation (SO) + physiological saline (Saline) + intravenous (iv) group; TCLP + Saline + iv group; HSO + SO2 + iv group; TCLP + SO2 + iv group; HSO + aCSF + NTS group; HSO + SO2 + NTS group; TCLP + aCSF + NTS group; HSO + SO2 + NTS group; TCLP + KYN + NTS group; HSO + aCSF + SO2 + NTS group; Group (pre-bilateral NTS injection of aCSF followed by injection of SO2 at the same site) 11SO + KYN + SO2 + NTS group (pre-bilateral NTS injection of KYN And then SO2 at the same site),5 min and 30 mi after administration, respectively. n3 The results were as follows:1. The cardiovascular effects of SO2 in the NTS and the RVLM: the dose-dependent decrease of the single-side micro-injection of SO2 in the NTS The effect of low blood pressure and slow heart rate (P <0.05). The dose-dependent rise of the single-side micro-injection of SO2 in the RVLM The effect of SO2 on the heart rate (P <0.05).2. The mechanism of the production of cardiovascular effect in the RVLM: the pre-RVLM injection of the KYN can partially block the SO2 (20 pmol). Cardiovascular effect induced by RVLM (P <0.05). Pre-RVLM injection of Gli, Nic, L-NAME or ODQ can effectively block the production of SO2 (20 pmol) in the RVLM The distribution of SO2 in the tissues and serum: the liver, the kidney, the heart, the brain and the serum of the sham operation group. The content of SO2 in the heart tissue was the highest in the heart, and the level of SO2 in the liver, the kidney, the heart, the brain and the serum of the rats after 3 h after the CLP model was compared with the sham operation group. The effect of SO 2 on the ABR in the rats with sepsis was higher than that in the same group. The results of the change of ABR in the same group were as follows: the results of the change of ABR in the same group were: the results of the changes of the ABR in the group of SO + SO2 + iv, CLP + SO2 + iv, SO + SO2 + NTS group, CLP + SO2 + NTS group, the SO + aCSF + SO2 + NTS group, and the ABR of the group of SO + aCSF + SO2 + NTS decreased significantly (P <0.05). The changes of ABR were significantly lower in the group of CLP + KYN + NTS (P <0.05). The results of the change of ABR were significantly lower than that in the group of SO + Saline + iv or the SO + SO 2 + iv group (P0.05). The CLP + aCSF + NTS group was significantly lower than that of the SO + aCSF. + NTS group or SO + SO2 + NTS group (P <0.05). The CLP + SO2 + iv group was significantly lower than that of the CLP + Saline + iv group (P <0.05) or the SO + Saline + iv group (P <0.05), and the CLP + SO2 + NTS group was significantly lower than that of the CLP + aCSF + NTS group (P <0.05) or the SO + aCSF + NTS group (P005), and the CLP + KYN + NTS group was significantly higher than that of the CLP + aCSF + NTS group (P <0.05), and the SO + KYN + SO2 + NTS group was significantly higher. 浜嶴O + aCSF + SO2 + NTS group (P <0.05). Conclusion:1 . SO2 can cause dose-dependent reduction of blood pressure and slow heart rate in the NTS. SO2 may cause a dose-dependent rise in hypertension and an accelerated heart rate in the RVLM. Involved in the regulation of central blood pressure, which may be related to the opening of KATP and L-type calcium channels. SO2 is produced in the RVLM 3. SO2 can be generated endogenously in normal rats, and the level of SO2 in cardiac tissue is higher than that of other groups. In rats, the level of SO2 in rats was higher than that of normal, and may be involved in the pathogenesis of sepsis rats.4. The increase in the production of 8O2 in vivo has a lower effect on the function of the ABR in septic rats, which can not only play a role in the peripheral venous system, but also may influence AB by the central NTS.
【學(xué)位授予單位】：蘭州大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2013
【分類號(hào)】：R459.7

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