【摘要】：目的： 1.研究氣態(tài)硫化合物二氧化硫(SO2)對(duì)腦卒中急診影響及季節(jié)性差異。 2.探討顆粒硫化合物硫酸鉛對(duì)人臍靜脈內(nèi)皮細(xì)胞(HUVEC)活力、RAS系統(tǒng)的影響。 3.闡明顆粒硫化合物硫酸鉛對(duì)SD大鼠血壓及RAS系統(tǒng)的影響及ACEI在其中的調(diào)控作用。 方法： 1.收集2008-2009年長(zhǎng)沙市湘雅三醫(yī)院每日腦卒中急診數(shù)據(jù)及相關(guān)氣象和大氣污染數(shù)據(jù),運(yùn)用單向回顧性1：4病例交叉設(shè)計(jì),分析不同季節(jié)S02對(duì)腦卒中急診事件的影響。 2.將人臍靜脈內(nèi)皮細(xì)胞(HUVEC)分為對(duì)照組和實(shí)驗(yàn)組,依據(jù)大氣細(xì)顆粒(PM2.5)中鉛的含量(0.042%),結(jié)合文獻(xiàn)設(shè)計(jì)低(0.17μg/ml)、中(0.85μg/ml)、高(4.25μg/ml)濃度硫酸鉛干預(yù)HUVEC24h。MTT法檢測(cè)細(xì)胞活力改變,普通逆轉(zhuǎn)錄PCR、western blot、ELISA檢測(cè)ACE、AngII、AT1R mRNA及蛋白表達(dá)的變化。 3.24只SD大鼠隨機(jī)分為對(duì)照組、硫酸鉛干預(yù)組、硫酸鉛+卡托普利組和卡托普利組。硫酸鉛+卡托普利組及卡托普利組予以卡托普利灌胃3d (100mg/(kg. d)),其他兩組予以灌胃相應(yīng)劑量生理鹽水；3d后,硫酸鉛干預(yù)組及硫酸鉛+卡托普利組予以氣管滴注硫酸鉛(84μg/kg),余兩組滴注相應(yīng)劑量生理鹽水。染毒1d后檢測(cè)大鼠血壓變化,ELISA檢測(cè)大鼠腹主動(dòng)脈血AngII、Ang (1-7)變化,普通逆轉(zhuǎn)錄PCR和western blot檢測(cè)大鼠心肌和胸主動(dòng)脈ACE、AT1R、ACE2. Mas mRNA和蛋白的改變。 結(jié)果： 1.在調(diào)整氣象因素(氣溫和相對(duì)濕度)的單污染物滯后模型中,秋季滯后0-3d的SO2日均濃度每增加10μ g/m3,總腦卒中及腦出血和腦梗死亞型急診OR值均大于1,且關(guān)聯(lián)具有統(tǒng)計(jì)學(xué)意義(P(0.05)；在同時(shí)控制NO2和PM10的多污染物模型中,秋季SO2濃度每增加10μ g/m3時(shí),總腦卒中和腦梗死急診的OR值(95%CI)為1.301(95%CI:1.038-1.631)、1.446(95%CI:1.130-1.850)(P0.05)。 2.HUVEC細(xì)胞暴露于低、中、高濃度硫酸鉛24h后,各組HUVEC細(xì)胞存活率較對(duì)照組均下降,但差異無(wú)統(tǒng)計(jì)學(xué)意義(P0.05)；各組ACE、及AT1R mRNA表達(dá)較對(duì)照組均升高,中、高濃度組與對(duì)照組差異有統(tǒng)計(jì)學(xué)意義(P0.05)；各組AT1R、AngII蛋白表達(dá)較對(duì)照組升高,中、高濃度組與對(duì)照組差異有統(tǒng)計(jì)學(xué)意義(P0.05)；中、高濃度組ACE蛋白表達(dá)較對(duì)照組升高,高濃度組與對(duì)照組差異有統(tǒng)計(jì)學(xué)意義(P0.05)。 3.硫酸鉛染毒后大鼠收縮壓及舒張壓均有所增加,其中舒張壓較對(duì)照組差異有統(tǒng)計(jì)學(xué)意義(P0.05),卡托普利預(yù)處理后可以顯著減弱硫酸鉛成分對(duì)大鼠舒張壓的影響(P0.05)；同時(shí)大鼠血漿AngII水平及心肌、主動(dòng)脈ACE、AT1R蛋白表達(dá)較對(duì)照組顯著升高(P0.05),但對(duì)大鼠血漿Ang(1-7)、心肌及主動(dòng)脈ACE2及Mas受體的影響無(wú)統(tǒng)計(jì)學(xué)意義(P0.05)；卡托普利預(yù)處理可以顯著減弱硫酸鉛對(duì)大鼠血漿AngII、心肌、主動(dòng)脈ACE及AT1R的影響(P0.05)。 結(jié)論： 1.研究區(qū)域秋季SO2日均濃度增加,導(dǎo)致腦卒中急診事件增多,對(duì)腦梗死急診事件影響更為顯著。 2.硫酸鉛可上調(diào)內(nèi)皮細(xì)胞ACE-AngII-AT1R軸mRNA和蛋白質(zhì)表達(dá)。 3.硫酸鉛急性暴露引起大鼠舒張壓顯著增高,同時(shí)激活大鼠心肌及主動(dòng)脈ACE-AngII-AT1R軸蛋白表達(dá),ACEI可降低硫酸鉛導(dǎo)致的血壓增高及ACE-AngII-AT1R軸蛋白的過(guò)度激活。
[Abstract]:Objective:
1. to study the effects of gaseous sulfur compounds sulfur dioxide (SO2) on stroke emergency and seasonal differences.
2. to investigate the effect of lead sulfate on human umbilical vein endothelial cells (HUVEC) and RAS system.
3. To clarify the effect of granular lead sulfate on blood pressure and RAS system in SD rats and the regulation of ACEI.
Method:
1. Daily emergency data of stroke and related meteorological and atmospheric pollution data of Changsha Xiangya Third Hospital from 2008 to 2009 were collected. The effects of S02 on emergency events of stroke in different seasons were analyzed by one-way retrospective 1:4 case crossover design.
2. Human umbilical vein endothelial cells (HUVEC) were divided into control group and experimental group. According to the content of lead in PM2.5 (0.042%), low (0.17 ug/ml), medium (0.85 ug/ml) and high (4.25 ug/ml) concentration of lead sulfate were designed to interfere with HUVEC 24 h. MTT assay was used to detect the changes of cell viability. Changes of mRNA and protein expression.
3.24 SD rats were randomly divided into control group, lead sulfate intervention group, lead sulfate + captopril group and captopril group. The blood pressure of rats was measured one day after exposure. AngII and Ang (1-7) in abdominal aorta blood were detected by ELISA. ACE, AT1R, ACE2.Mas mRNA and protein in myocardium and thoracic aorta were detected by RT-PCR and Western blot.
Result:
1. In the single pollutant hysteresis model with adjusted meteorological factors (air temperature and relative humidity), the OR values of total stroke, cerebral hemorrhage and cerebral infarction subtypes were higher than 1 for each increase of 10 ug/m3 of SO2 concentration per day with 0-3 days lag in autumn, and the correlation was statistically significant (P (0.05); in the multi-pollutant model with simultaneous control of NO2 and PM 10, the concentration of SO2 in autumn was higher than 1. The OR values of total stroke and cerebral infarction emergency (95% CI) were 1.301 (95% CI: 1.038-1.631) and 1.446 (95% CI: 1.130-1.850) (P 0.05).
2. HUVEC cells exposed to low, medium and high concentrations of lead sulfate 24 hours later, the survival rate of HUVEC cells in each group decreased, but the difference was not statistically significant (P 0.05); ACE, and AT1R mRNA expression in each group were higher than that in the control group, the difference was statistically significant (P 0.05); AT1R, AngII protein expression in each group was higher than that in the control group. The expression of ACE protein in high concentration group was significantly higher than that in control group (P 0.05).
3. The systolic and diastolic blood pressures of rats exposed to lead sulfate were increased, and the diastolic blood pressure was significantly higher than that of the control group (P There was no significant difference in plasma Ang (1-7), myocardial and aortic ACE2 and Mas receptors (P 0.05). Captopril pretreatment could significantly attenuate the effects of lead sulfate on plasma AngII, myocardial, aortic ACE and AT1R (P 0.05).
Conclusion:
1. The increase of SO2 concentration in the study area in autumn led to the increase of stroke emergency events, and the impact on cerebral infarction emergency events was more significant.
2. lead sulfate can increase the expression of mRNA and protein in ACE-AngII-AT1R axis of endothelial cells.
3. Acute exposure to lead sulfate can increase diastolic blood pressure and activate ACE-AngII-AT1R axon protein expression in myocardium and aorta of rats. ACEI can decrease lead sulfate-induced hypertension and ACE-AngII-AT1R axon overactivation.
【學(xué)位授予單位】：中南大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2014
【分類號(hào)】：R743.3

【共引文獻(xiàn)】

相關(guān)期刊論文 前10條

1 曾敬;蘆茜;陳墾;姚勇剛;張駿;曾春雨;;大氣細(xì)顆粒物對(duì)G蛋白偶聯(lián)受體激酶4的異常調(diào)節(jié)在尿鈉排泄中的作用[J];第三軍醫(yī)大學(xué)學(xué)報(bào);2014年10期

2 趙洋;董光輝;;大氣污染對(duì)血壓影響研究進(jìn)展[J];環(huán)境與健康雜志;2013年07期

3 張保生;張婉婷;;包頭市環(huán)境空氣中PM_(2.5)源解析研究[J];環(huán)境工程;2014年04期

4 Jerome E.McGinnis;Jongbae Heo;Michael R.Olson;Andrew P.Rutter;James J.Schauer;;Understanding the sources and composition of the incremental excess of fine particles across multiple sampling locations in one air shed[J];Journal of Environmental Sciences;2014年04期

5 郭辰;劉濤;趙曉紅;;大氣細(xì)顆粒物的健康危害機(jī)制及拮抗作用研究進(jìn)展[J];環(huán)境與健康雜志;2014年02期

6 周穎;徐興祥;閔凌峰;;大氣污染對(duì)心血管疾病的影響研究進(jìn)展[J];實(shí)用醫(yī)學(xué)雜志;2014年03期

7 朱秀萍;張彩鳳;么太成;王艷;邵仲達(dá);李艷麗;袁淑青;王德軍;秦天榜;吳壽嶺;;肺灌洗對(duì)塵肺患者血壓變化的影響[J];中華高血壓雜志;2013年07期

8 劉陽(yáng);黃嵐;;缺氧對(duì)腎素-血管緊張素系統(tǒng)影響的研究進(jìn)展[J];中國(guó)分子心臟病學(xué)雜志;2014年01期

9 熊紜輝;黃宜生;洪文彬;;老年高血壓患者腎微循環(huán)功能障礙與脈壓、血脂及高敏C反應(yīng)蛋白的關(guān)系[J];中國(guó)老年學(xué)雜志;2014年11期

10 吳宏力;魯軍;佘星星;孫冰潔;任迪峰;;血管緊張素轉(zhuǎn)換酶2-血管緊張素(1-7)-Mas軸的血壓調(diào)控作用研究進(jìn)展[J];中華高血壓雜志;2014年06期

相關(guān)博士學(xué)位論文 前5條

1 孫e，

本文編號(hào)：2231118