右側(cè)頸交感神經(jīng)干離斷聯(lián)合不同鎮(zhèn)痛藥物對大鼠心梗后心室重構(gòu)的保護(hù)作用及機(jī)制研究
發(fā)布時間：2018-07-24 18:11
【摘要】：第一部分右側(cè)頸交感神經(jīng)干離斷聯(lián)合不同鎮(zhèn)痛藥物對大鼠心肌梗死后心室重構(gòu)的影響目的探索右側(cè)頸交感神經(jīng)干離斷聯(lián)合不同鎮(zhèn)痛藥物(帕瑞昔布、氟比洛芬酯、嗎啡)對大鼠心肌梗死后心室重構(gòu)的影響。方法采用結(jié)扎心臟冠狀動脈前降支的方式構(gòu)建MI模型及離斷右側(cè)頸交感神經(jīng)干的方法建立TCST模型,36只雄性SD大鼠隨機(jī)分為6組(n=6):Sham組、MI組、TCST組、TCST+P組、TCST+F組、TCST+M組。MI及右TCST建模后,TCST+P組、TCST+F組、TCST+M組大鼠分別腹腔注射12 mg/kg帕瑞昔布、15 mg/kg氟比洛芬酯、1.2 mg/kg嗎啡,2次/d,共3d。于建模處置4周超聲心動圖檢測各組大鼠的心臟功能變化;右側(cè)頸動脈插管的方法測定大鼠血流動力學(xué)結(jié)果;處死大鼠,取心臟測定左室肥厚指數(shù);HE染色、Masson染色觀測梗死周邊區(qū)心肌組織病理變化和間質(zhì)膠原蛋白增生情況;Sq RT-PCR法檢測梗死周邊區(qū)心肌ANP m RNA、BNP m RNA含量的變化;q RT-PCR法檢測梗死區(qū)心肌炎癥因子IL-6 m RNA、TNF-αm RNA的表達(dá)。結(jié)果1心功能結(jié)果:與Sham組比較,MI組大鼠心功能指標(biāo)LVEDd、LVESd顯著增加,LVEF、LVFS顯著減少(P0.05);與MI組比較,各治療組LVEDd、LVESd降低,LVEF、LVFS升高(P0.05);與TCST組比較,TCST+P組、TCST+F組、TCST+M組LVEDd、LVESd降低,LVEF、LVFS升高,其中TCST+M組心功能改善最顯著(P0.05)。2血流動力學(xué)結(jié)果:與Sham組比較,MI組大鼠心功能指標(biāo)LVSP、+dp/dtmax顯著降低,LVEDP、-dp/dtmax顯著升高(P0.05);與MI組比較,各治療組LVSP、+dp/dtmax升高,LVEDP、-dp/dtmax降低(P0.05);與TCST組比較,TCST+P組、TCST+F組、TCST+M組LVSP、+dp/dtmax升高,LVEDP、-dp/dtmax降低,其中TCST+M組血流動力學(xué)改善效果最明顯(P0.05)。3左室肥厚指數(shù)改變:與Sham組比較,MI組體重降低,左室肥厚指數(shù)各指標(biāo)HW/BW、(LV+S)/BW、(LV+S)/HW升高(P0.05);與MI組比較,單用TCST治療組體重升高,左室肥厚指數(shù)各指標(biāo)降低(P0.05);與TCST組比較,TCST+P組、TCST+F組、TCST+M組體重升高,左室肥厚指數(shù)各指標(biāo)降低,其中TCST+M組左室肥厚指數(shù)降低最明顯(P0.05)。4心肌組織形態(tài)學(xué)改變:Sham組心肌細(xì)胞排列有序,無斷裂,顯示正常心肌細(xì)胞形態(tài);MI組梗死周邊區(qū)心肌細(xì)胞腫脹增粗最顯著,排列紊亂,細(xì)胞間隙出現(xiàn)大量膠原蛋白增生,呈網(wǎng)狀分布,炎性細(xì)胞浸潤明顯,膠原容積分?jǐn)?shù)CVF增多(P0.05);單用TCST治療組心肌細(xì)胞排列紊亂及間質(zhì)纖維化水平有明顯減輕,CVF較MI組降低(P0.05);TCST+P組、TCST+F組、TCST+M組梗死周邊區(qū)心肌細(xì)胞排列較有序,間質(zhì)纖維降低,炎性細(xì)胞浸潤進(jìn)一步減輕,CVF較TCST組降低,其中TCST+M組病理改善效果最明顯(P0.05)。5梗死周邊區(qū)ANP m RNA、BNP m RNA改變:與Sham組比較,MI組梗死周邊區(qū)心肌肥厚標(biāo)志物基因ANP m RNA、BNP m RNA的表達(dá)升高(P0.05);與MI組比較,TCST干預(yù)可降低ANP m RNA、BNP m RNA的表達(dá)(P0.05);與TCST組比較,TCST+P組、TCST+F組、TCST+M組ANP m RNA、BNP m RNA的表達(dá)降低,其中TCST+M組降低最顯著(P0.05)。6梗死區(qū)IL-6 m RNA、TNF-αm RNA的表達(dá)變化:與Sham組比較,MI組梗死區(qū)炎癥因子IL-6 m RNA、TNF-αm RNA的表達(dá)升高(P0.05);與MI組比較,TCST干預(yù)可降低IL-6 m RNA、TNF-αm RNA的表達(dá)(P0.05);與TCST組比較,TCST+P組、TCST+F組、TCST+M組IL-6 m RNA、TNF-αm RNA的表達(dá)降低,其中TCST+M組降低最顯著(P0.05)。結(jié)論1單用TCST及TCST與帕瑞昔布、氟比洛芬酯、嗎啡聯(lián)合治療均可提高大鼠心肌梗死后心肌舒縮功能,一定程度上減輕心肌肥厚、間質(zhì)纖維化,延緩心室重構(gòu)過程。2 TCST與帕瑞昔布、氟比洛芬酯、嗎啡聯(lián)合治療延緩大鼠心梗后心室重構(gòu)的效果優(yōu)于單用TCST治療,且以TCST聯(lián)合嗎啡改善心室重構(gòu)的效果最優(yōu)。3 TCST同帕瑞昔布、氟比洛芬酯、嗎啡聯(lián)合治療延緩MI后心室重構(gòu)的機(jī)制可能與其強(qiáng)烈的鎮(zhèn)痛作用降低了交感神經(jīng)系統(tǒng)的活性;降低炎癥因子IL-6、TNF-α的表達(dá),減少炎癥反應(yīng)有關(guān)。第二部分右側(cè)頸交感神經(jīng)干離斷聯(lián)合不同鎮(zhèn)痛藥物對大鼠心肌梗死后PI3K/Akt信號通路的影響目的探討右側(cè)頸交感神經(jīng)干離斷聯(lián)合不同鎮(zhèn)痛藥物(帕瑞昔布、氟比洛芬酯、嗎啡)對大鼠心肌梗死后PI3K/Akt信號通路的影響。方法采用結(jié)扎心臟冠狀動脈前降支的方式構(gòu)建MI模型及離斷右側(cè)頸交感神經(jīng)干的方法建立TCST模型,36只雄性SD大鼠隨機(jī)分為6組(n=6):Sham組、MI組、TCST組、TCST+P組、TCST+F組、TCST+M組。MI及右TCST建模后,TCST+P組、TCST+F組、TCST+M組大鼠分別腹腔注射12 mg/kg帕瑞昔布、15 mg/kg氟比洛芬酯、1.2 mg/kg嗎啡,2次/d,共3d。于建模4周時處死大鼠,取心臟進(jìn)行Tunel染色,光鏡下觀測心肌細(xì)胞凋亡情況;Western Blot法測定心肌PI3K、Akt、p-Akt、pro-caspase3、caspase3的蛋白表達(dá)。結(jié)果1心肌細(xì)胞凋亡的測定結(jié)果:與Sham組比較,MI組在梗死周邊區(qū)及遠(yuǎn)隔梗死區(qū)組織都存在許多的心肌細(xì)胞發(fā)生凋亡,周邊區(qū)凋亡指數(shù)AI明顯增加(P0.05);與MI組比較,經(jīng)TCST處理后梗死周邊區(qū)及遠(yuǎn)隔梗死區(qū)組織心肌細(xì)胞凋亡發(fā)生明顯減少,周邊區(qū)AI下降(P0.05);與TCST組比較,TCST+P組、TCST+F組、TCST+M組梗死周邊區(qū)及遠(yuǎn)隔梗死區(qū)組織凋亡的心肌細(xì)胞進(jìn)一步降低(P0.05),其中TCST+M組梗死周邊區(qū)組織AI下降最顯著(P0.05)。2 PI3K/Akt信號通路蛋白表達(dá)的改變:各組Akt、pro-caspase3蛋白表達(dá)無顯著差異(P0.05)。與Sham組比較,MI組梗死區(qū)組織PI3K、p-Akt蛋白表達(dá)均顯著下降,caspase3蛋白表達(dá)顯著上升(P0.05);與MI組比較,TCST干預(yù)可提高PI3K、p-Akt蛋白表達(dá),降低caspase3蛋白表達(dá)(P0.05);與TCST組比較,TCST+P組、TCST+F組、TCST+M組PI3K、p-Akt蛋白表達(dá)均增加,caspase3蛋白表達(dá)降低(P0.05)。結(jié)論TCST同帕瑞昔布、氟比洛芬酯、嗎啡聯(lián)合治療延緩MI后心室重構(gòu)的機(jī)制可能通過增強(qiáng)PI3K/Akt抗凋亡信號通路的表達(dá),下調(diào)細(xì)胞凋亡蛋白caspase3,抑制心肌細(xì)胞凋亡有關(guān)。
[Abstract]:The effect of the right cervical sympathetic nerve dry dissociation combined with different analgesic drugs on ventricular remodeling after myocardial infarction in rats objective to explore the effect of the right cervical sympathetic trunk disconnection combined with different analgesic drugs (pareoxib, flurbiprofen ester, morphine) on the ventricular restructure after myocardial infarction in rats. Methods the ligature of the coronary artery before the coronary artery was ligated. The MI model and the right cervical sympathetic trunk were constructed by the way of descending branch. 36 male SD rats were randomly divided into 6 groups (n=6): Sham group, MI group, TCST group, TCST+P group, TCST+F group, TCST+M group.MI and right TCST. The rats were intraperitoneally injected with 12 palioxib and 15 flurbiprofen, respectively. Ester, 1.2 mg/kg morphine, 2 times /d, CO 3D. was used to detect cardiac function changes in each group by modeling and disposing 4 weeks echocardiography. The right carotid intubation method was used to determine the hemodynamic results of rats. The rats were killed and the left ventricular hypertrophy index was measured by the heart. HE staining and Masson staining were used to observe the pathological changes of myocardium and interstitial collagen in the surrounding area of the infarct. Sq RT-PCR assay was used to detect the changes of ANP m RNA, BNP m RNA content in the peri infarct zone; Q RT-PCR assay was used to detect the infarct zone myocarditis factor IL-6 m. LVEDd, LVESd, LVEF and LVFS increased (P0.05) in the treatment group. Compared with the TCST group, the TCST+P group, TCST+F group, TCST+M group LVEDd, LVESd decreased, LVEF, and increased. Increase (P0.05); compared with group MI, LVSP, +dp/dtmax, LVEDP, -dp/dtmax decreased (P0.05) in the treatment group, and TCST+P group, TCST+F group and TCST+M group were compared with TCST group. The index of left ventricular hypertrophy index HW/BW, (LV+S) /BW, (LV+S) /HW increased (P0.05). Compared with the MI group, the weight of the left ventricular hypertrophy index was lower (P0.05), and the weight of the TCST+P group, TCST+F group and the left ventricular hypertrophy index were lower than those in the TCST treatment group. .05).4 myocardial histomorphological changes: the myocardial cells in group Sham were arranged in order, without breakage, showing normal cardiac myocyte morphology. The most significant swelling and thickening of myocardial cells in the peripheral area of the MI group was disorderly, a large number of collagen proliferated in the intercellular space, a network distribution, obvious infiltration of inflammatory cells, and increased collagen volume fraction CVF increased (P0.05) alone (P0.05). The myocardial cell arrangement disorder and the level of interstitial fibrosis in the TCST treatment group were significantly reduced, and the CVF was lower than that in the MI group (P0.05). The myocardial cells in the peripheral area of the infarction group, group TCST+P, group TCST+F, and group TCST+M were arranged in a more orderly manner, the interstitial fiber decreased, the infiltration of inflammatory cells was further reduced, and the CVF was lower than the TCST group. The pathological improvement effect of the TCST+M group was most obvious (P0.05).5 ANP m RNA, BNP m RNA changes in the peripheral area of infarct: compared with the Sham group, the expression of ANP m RNA in the peripheral zone of infarct zone in MI group is higher than that in the infarction group. TCST+M group decreased the most significant (P0.05).6 infarct area IL-6 m RNA, TNF- alpha m RNA expression change: compared with the Sham group, the inflammatory factor in the MI group was higher than that in the MI group. The expression of RNA, TNF- alpha m RNA decreased, of which the TCST+M group decreased most significantly (P0.05). Conclusion 1 single use of TCST and TCST with pareoxib, flurbiprofen and morphine can improve myocardial systolic and diastolic function in rats after myocardial infarction, to a certain extent, reduce myocardial hypertrophy, interstitial fibrosis, and delay the process of ventricular remodeling,.2 TCST and pareoxib, fluoro ratio. The effect of combined therapy on ventricular remodeling after myocardial infarction in rats is better than that of TCST alone, and the best effect of TCST combined with morphine to improve ventricular remodeling, the mechanism of.3 TCST with pareoxib, flurbiprofen and morphine for delayed ventricular remodeling after MI may reduce the sympathetic nervous system with its strong analgesic effect. Activity; reducing the expression of inflammatory factors IL-6, TNF- alpha and reducing inflammatory response. Second the effect of the right cervical sympathetic trunk disconnection combined with different analgesic drugs on the PI3K/Akt signaling pathway in rats after myocardial infarction; objective to explore the right cervical sympathetic trunk disconnection combined with different analgesic drugs (pareoxib, flurbiprofen ester, morphine) The effect of PI3K/Akt signaling pathway after myocardial infarction in rats. Methods the MI model and the right cervical sympathetic trunk were established by ligating the anterior descending branch of the heart coronary artery to establish the TCST model. 36 male SD rats were randomly divided into 6 groups (n=6): Sham group, MI group, TCST group, TCST+P group, TCST+F group, TCST+M group.MI and right modeling Group TCST+F, group TCST+F, group TCST+M rats were intraperitoneally injected with 12 mg/kg parinoxib, 15 mg/kg flurbiprofen ester, 1.2 mg/kg morphine and 2 /d. The rats were killed at the 4 week of modeling, and Tunel staining was carried out in the heart. The apoptosis of cardiac myocytes was observed under light microscope. Western Blot method was used to detect the PI3K, Akt, protein expression. The results of apoptosis of 1 cardiac myocytes: compared with the Sham group, there were many cardiomyocytes in the peripheral and distant infarct regions of the MI group, and the apoptosis index AI in the peripheral region was significantly increased (P0.05). Compared with the MI group, the apoptosis of the myocardial cells in the peri infarct zone and the distal septum tissue was significantly decreased after TCST treatment. AI decreased in the border area (P0.05). Compared with the TCST group, the myocardial cells with apoptosis in the peripheral infarct area and the infarct area in group TCST+P, TCST+F and TCST+M were further reduced (P0.05), and the decrease of AI in the tissue around the infarct zone was the most significant (P0.05) the change of the expression of the pathway protein in the.2 PI3K/Akt signal: there was no significant expression of the protein in each group. Difference (P0.05). Compared with group Sham, the expression of PI3K in the infarct area of group MI was significantly decreased, and the expression of Caspase3 protein increased significantly (P0.05). Compared with the MI group, TCST intervention could improve the expression of PI3K, p-Akt protein and decrease the expression of Caspase3 protein. The expression of aspase3 protein was reduced (P0.05). Conclusion the mechanism of TCST with pareoxib, flurbiprofen ester and morphine in the treatment of MI ventricular remodeling may be mediated by enhancing the expression of PI3K/Akt anti apoptotic signaling pathway, lowering the apoptosis protein Caspase3 and inhibiting the apoptosis of cardiac myocytes.
【學(xué)位授予單位】：重慶醫(yī)科大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：R614
[Abstract]:The effect of the right cervical sympathetic nerve dry dissociation combined with different analgesic drugs on ventricular remodeling after myocardial infarction in rats objective to explore the effect of the right cervical sympathetic trunk disconnection combined with different analgesic drugs (pareoxib, flurbiprofen ester, morphine) on the ventricular restructure after myocardial infarction in rats. Methods the ligature of the coronary artery before the coronary artery was ligated. The MI model and the right cervical sympathetic trunk were constructed by the way of descending branch. 36 male SD rats were randomly divided into 6 groups (n=6): Sham group, MI group, TCST group, TCST+P group, TCST+F group, TCST+M group.MI and right TCST. The rats were intraperitoneally injected with 12 palioxib and 15 flurbiprofen, respectively. Ester, 1.2 mg/kg morphine, 2 times /d, CO 3D. was used to detect cardiac function changes in each group by modeling and disposing 4 weeks echocardiography. The right carotid intubation method was used to determine the hemodynamic results of rats. The rats were killed and the left ventricular hypertrophy index was measured by the heart. HE staining and Masson staining were used to observe the pathological changes of myocardium and interstitial collagen in the surrounding area of the infarct. Sq RT-PCR assay was used to detect the changes of ANP m RNA, BNP m RNA content in the peri infarct zone; Q RT-PCR assay was used to detect the infarct zone myocarditis factor IL-6 m. LVEDd, LVESd, LVEF and LVFS increased (P0.05) in the treatment group. Compared with the TCST group, the TCST+P group, TCST+F group, TCST+M group LVEDd, LVESd decreased, LVEF, and increased. Increase (P0.05); compared with group MI, LVSP, +dp/dtmax, LVEDP, -dp/dtmax decreased (P0.05) in the treatment group, and TCST+P group, TCST+F group and TCST+M group were compared with TCST group. The index of left ventricular hypertrophy index HW/BW, (LV+S) /BW, (LV+S) /HW increased (P0.05). Compared with the MI group, the weight of the left ventricular hypertrophy index was lower (P0.05), and the weight of the TCST+P group, TCST+F group and the left ventricular hypertrophy index were lower than those in the TCST treatment group. .05).4 myocardial histomorphological changes: the myocardial cells in group Sham were arranged in order, without breakage, showing normal cardiac myocyte morphology. The most significant swelling and thickening of myocardial cells in the peripheral area of the MI group was disorderly, a large number of collagen proliferated in the intercellular space, a network distribution, obvious infiltration of inflammatory cells, and increased collagen volume fraction CVF increased (P0.05) alone (P0.05). The myocardial cell arrangement disorder and the level of interstitial fibrosis in the TCST treatment group were significantly reduced, and the CVF was lower than that in the MI group (P0.05). The myocardial cells in the peripheral area of the infarction group, group TCST+P, group TCST+F, and group TCST+M were arranged in a more orderly manner, the interstitial fiber decreased, the infiltration of inflammatory cells was further reduced, and the CVF was lower than the TCST group. The pathological improvement effect of the TCST+M group was most obvious (P0.05).5 ANP m RNA, BNP m RNA changes in the peripheral area of infarct: compared with the Sham group, the expression of ANP m RNA in the peripheral zone of infarct zone in MI group is higher than that in the infarction group. TCST+M group decreased the most significant (P0.05).6 infarct area IL-6 m RNA, TNF- alpha m RNA expression change: compared with the Sham group, the inflammatory factor in the MI group was higher than that in the MI group. The expression of RNA, TNF- alpha m RNA decreased, of which the TCST+M group decreased most significantly (P0.05). Conclusion 1 single use of TCST and TCST with pareoxib, flurbiprofen and morphine can improve myocardial systolic and diastolic function in rats after myocardial infarction, to a certain extent, reduce myocardial hypertrophy, interstitial fibrosis, and delay the process of ventricular remodeling,.2 TCST and pareoxib, fluoro ratio. The effect of combined therapy on ventricular remodeling after myocardial infarction in rats is better than that of TCST alone, and the best effect of TCST combined with morphine to improve ventricular remodeling, the mechanism of.3 TCST with pareoxib, flurbiprofen and morphine for delayed ventricular remodeling after MI may reduce the sympathetic nervous system with its strong analgesic effect. Activity; reducing the expression of inflammatory factors IL-6, TNF- alpha and reducing inflammatory response. Second the effect of the right cervical sympathetic trunk disconnection combined with different analgesic drugs on the PI3K/Akt signaling pathway in rats after myocardial infarction; objective to explore the right cervical sympathetic trunk disconnection combined with different analgesic drugs (pareoxib, flurbiprofen ester, morphine) The effect of PI3K/Akt signaling pathway after myocardial infarction in rats. Methods the MI model and the right cervical sympathetic trunk were established by ligating the anterior descending branch of the heart coronary artery to establish the TCST model. 36 male SD rats were randomly divided into 6 groups (n=6): Sham group, MI group, TCST group, TCST+P group, TCST+F group, TCST+M group.MI and right modeling Group TCST+F, group TCST+F, group TCST+M rats were intraperitoneally injected with 12 mg/kg parinoxib, 15 mg/kg flurbiprofen ester, 1.2 mg/kg morphine and 2 /d. The rats were killed at the 4 week of modeling, and Tunel staining was carried out in the heart. The apoptosis of cardiac myocytes was observed under light microscope. Western Blot method was used to detect the PI3K, Akt, protein expression. The results of apoptosis of 1 cardiac myocytes: compared with the Sham group, there were many cardiomyocytes in the peripheral and distant infarct regions of the MI group, and the apoptosis index AI in the peripheral region was significantly increased (P0.05). Compared with the MI group, the apoptosis of the myocardial cells in the peri infarct zone and the distal septum tissue was significantly decreased after TCST treatment. AI decreased in the border area (P0.05). Compared with the TCST group, the myocardial cells with apoptosis in the peripheral infarct area and the infarct area in group TCST+P, TCST+F and TCST+M were further reduced (P0.05), and the decrease of AI in the tissue around the infarct zone was the most significant (P0.05) the change of the expression of the pathway protein in the.2 PI3K/Akt signal: there was no significant expression of the protein in each group. Difference (P0.05). Compared with group Sham, the expression of PI3K in the infarct area of group MI was significantly decreased, and the expression of Caspase3 protein increased significantly (P0.05). Compared with the MI group, TCST intervention could improve the expression of PI3K, p-Akt protein and decrease the expression of Caspase3 protein. The expression of aspase3 protein was reduced (P0.05). Conclusion the mechanism of TCST with pareoxib, flurbiprofen ester and morphine in the treatment of MI ventricular remodeling may be mediated by enhancing the expression of PI3K/Akt anti apoptotic signaling pathway, lowering the apoptosis protein Caspase3 and inhibiting the apoptosis of cardiac myocytes.
【學(xué)位授予單位】：重慶醫(yī)科大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：R614
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相關(guān)期刊論文 前10條
1 雷遷;呂娟娟;梁杰賢;周成斌;王晟;;星狀神經(jīng)節(jié)阻滯對兔心肌梗死后心功能的影響[J];嶺南心血管病雜志;2016年01期
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本文編號：2142225
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