本文選題：犬 + 急性心房顫動(dòng)�。� 參考：《西南醫(yī)科大學(xué)》2017年碩士論文

【摘要】：目的:研究犬急性房顫模型中HCN通道亞單位(HCN2和HCN4)基因和蛋白表達(dá)及超級(jí)化激活電流(If)的變化在致電重構(gòu)后對(duì)急性房顫發(fā)生的影響。探討HCN通道特異性阻滯劑-伊伐布雷定對(duì)抑制急性房顫發(fā)生及維持的作用。方法:將18只犬隨機(jī)分為三組,空白對(duì)照組(n=6),刺激組(n=6),刺激+伊伐布雷定組(n=6)�？瞻讓�(duì)照組僅行電極標(biāo)測(cè)記錄;刺激組給予快速起搏心房6h;刺激+伊伐布雷定組給以6h快速心房起搏過(guò)程中持續(xù)靜脈泵入伊伐布雷定(0.5mg/kg/h),成功建模后檢測(cè)三組犬心率及心臟電生理的變化,取心臟不同部位樣本(左右心房及左右心耳),采用Real-time PCR檢測(cè)三組HCN2及HCN4 m RNA的表達(dá)變化,Western-blotting檢測(cè)HCN2及HCN4的蛋白含量,全細(xì)胞膜片鉗技術(shù)檢測(cè)單個(gè)心房肌細(xì)胞上If的改變。結(jié)果:空白對(duì)照組犬心率不隨時(shí)間的推移而改變,刺激組心率隨實(shí)驗(yàn)時(shí)間推移而升高,刺激+伊伐布雷定組心率隨實(shí)驗(yàn)時(shí)間推移下降,三組差異有統(tǒng)計(jì)學(xué)意義(P0.01)。經(jīng)6小時(shí)快速心房起搏后,刺激組房顫誘發(fā)率及房顫持續(xù)的時(shí)間較對(duì)照組均明顯升高,房顫誘發(fā)率為46.67%vs.14.67%,(P0.01),房顫持續(xù)時(shí)間為700±309.84s vs.120±58.99s,(P0.01)。而刺激+伊伐布雷定組的房顫誘發(fā)率及房顫持續(xù)時(shí)間則回將至8.67%及105±51.67s,其差異與刺激組相比有統(tǒng)計(jì)學(xué)意義(P0.01)。對(duì)照組有效不應(yīng)期隨時(shí)間改變無(wú)明顯變化,刺激組有效不應(yīng)期隨起搏時(shí)間時(shí)間明顯進(jìn)行性縮短,差異有統(tǒng)計(jì)學(xué)意義(p0.01)。相反,刺激+伊伐布雷定組有效不應(yīng)期隨時(shí)間進(jìn)行性延長(zhǎng),與刺激組對(duì)比,差別有統(tǒng)計(jì)學(xué)意義(p0.01)。在心房不同部位,與對(duì)照組相比,刺激組左心房(la)、右心房(ra)、左心耳(laa)、右心耳(raa)內(nèi)hcn2和hcn4通道的mrna表達(dá)水平增加,差異具有統(tǒng)計(jì)學(xué)意義(p0.01)。與刺激組相比,刺激+伊伐布雷定組左心房(la)、右心房(ra)、左心耳(laa)、右心耳(raa)內(nèi)hcn2和hcn4通道的mrna表達(dá)降低,差異具有統(tǒng)計(jì)學(xué)意義(p0.01)。同樣刺激組相對(duì)于對(duì)照組左心房(la)、右心房(ra)、左心耳(laa)、右心耳(raa)內(nèi)hcn2和hcn4通道的蛋白含量表達(dá)增加,差異具有統(tǒng)計(jì)學(xué)意義(p0.01)。與刺激組相比,刺激+伊伐布雷定組左心房(la)、右心房(ra)、左心耳(laa)、右心耳(raa)內(nèi)hcn2和hcn4通道的蛋白含量表達(dá)降低,差異具有統(tǒng)計(jì)學(xué)意義(p0.01)。在全細(xì)胞的if電流記錄時(shí)顯示,刺激組犬心房肌細(xì)胞的if電流比對(duì)照組if電流明顯增大(5.19±0.60pa/pfvs2.68±0.30pa/pf,p0.01),與刺激組相比,給予伊伐布雷定后的犬心房肌細(xì)胞電流明顯減小至2.17±0.63pa/pf,p0.01。提示hcn通道功能活動(dòng)與表達(dá)在用藥后發(fā)生抑制變化。結(jié)論:1.急性房顫發(fā)生時(shí),hcn通道基因和蛋白表達(dá)上調(diào),if電流增大。2.伊伐布雷定可以降低心率,延長(zhǎng)心房有效不應(yīng)期,降低房顫誘發(fā)率,縮短房顫持續(xù)時(shí)間。3.伊伐布雷定可以通過(guò)抑制HCN2和HCN4通道表達(dá),減小If電流來(lái)抑制心房組織電重構(gòu),從而抑制急性房顫的發(fā)生。
[Abstract]:Aim: to investigate the effects of HCN channel subunits (HCN2 and HCN4) on the occurrence of acute atrial fibrillation (AAF) in canine acute atrial fibrillation (AAF) model.To investigate the effect of HCN channel specific blocker (Evasbradide) on inhibiting the occurrence and maintenance of acute atrial fibrillation (AAF).Methods: eighteen dogs were randomly divided into three groups: control group (n = 6), stimulation group (n = 6) and ivalburetine group (n = 6).The blank control group was only recorded by electrode mapping.The stimulation group was given rapid atrial pacing for 6 hours, and the Ifabradine group was given continuous intravenous infusion of 0.5 mg / kg 路kg / h of ivalburetine during 6 h rapid atrial pacing. The heart rate and cardiac electrophysiology of the three groups were measured after successful modeling.The expression changes of HCN2 and HCN4 m RNA in three groups were detected by Real-time PCR. The protein contents of HCN2 and HCN4 were detected by Western-blotting, and the changes of if on single atrial myocytes were detected by whole-cell patch clamp technique.Results: the heart rate of the blank control group did not change with the passage of time, but the heart rate of the stimulation group increased with the passage of experimental time, and the heart rate of the Evalburetine group decreased with the passage of the experimental time. The difference among the three groups was statistically significant (P 0.01).After 6 hours of rapid atrial pacing, the atrial fibrillation evoked rate and the duration of atrial fibrillation in the stimulation group were significantly higher than those in the control group. The atrial fibrillation evoked rate was 46.67 vs.14.67p0.01g, and the duration of atrial fibrillation was 700 鹵309.84s vs.120 鹵58.99s (P 0.01).The rate of atrial fibrillation induced and the duration of atrial fibrillation in the treatment group were 8.67% and 105 鹵51.67 s respectively, and the difference was statistically significant compared with the stimulation group (P 0.01).In the control group, the effective refractory period did not change significantly with time, while in the stimulation group, the effective refractory period was significantly shortened with the pacing time, and the difference was statistically significant (p 0.01).On the contrary, the effective refractory period of Ifabradine group was prolonged progressively with time, compared with the stimulation group, the difference was statistically significant (p 0.01).Compared with the control group, the mrna expression levels of hcn2 and hcn4 channels in the stimulation group were significantly higher than those in the control group (P < 0.01), and the expression levels of hcn2 and hcn4 channels in the stimulation group were significantly higher than those in the control group (P < 0.01), and the expression levels of mrna and hcn4 channels in the stimulation group were significantly higher than those in the control group (P < 0.01).Compared with the stimulation group, the mrna expression of hcn2 and hcn4 channels in the Ifabradine group was significantly lower than that in the control group (P < 0.01).The protein expression of hcn2 and hcn4 channels in the same stimulation group was significantly higher than that in the control group (P 0.01).Compared with the stimulation group, the protein expression of hcn2 and hcn4 channels in the left atrium, right atrium, left atrial Aura, right atrial auricle and right atrial auricle were decreased in the treatment group, and the difference was statistically significant (P 0.01).The if current recorded in the whole cell showed that the if current in the stimulation group was significantly higher than that in the control group (5.19 鹵0.30PA / pffp0.01g). Compared with the stimulation group, the current of the canine atrial myocytes treated with ivalburetine was significantly decreased to 2.17 鹵0.63pa-pfp0.01.The results suggest that the function and expression of hcn channel are inhibited after medication.Conclusion 1.During the occurrence of acute atrial fibrillation, the gene and protein expression of HCN channel upregulated the if current. 2. 2.Ifabradine can reduce heart rate, prolong atrial effective refractory period, reduce atrial fibrillation induced rate, and shorten atrial fibrillation duration by 3. 3.Ifabradine can inhibit the electrical remodeling of atrial tissue by inhibiting the expression of HCN2 and HCN4 channels and decreasing the if current, thus inhibiting the occurrence of acute atrial fibrillation.
【學(xué)位授予單位】：西南醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類(lèi)號(hào)】：R541.75

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