组蛋白去乙酰化酶SIRT1在不同类型房颤患者中的作用机制研究
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摘要
第一部分
风湿性心脏病合并房颤患者心房组织组蛋白去乙酰化酶SIRT1表达与心房纤维化的相关性研究
目的通过观察房颤患者心房肌组织SIRT1的表达情况、心房肌纤维化的程度,SIRT1与心房纤维化的相关关系,了解房颤患者心房肌组织SIRT1的表达及其与心房纤维化的相关性,并通过检测心房肌组织p53蛋白的表达情况,了解房颤患者心房肌组织SIRT1表达参与房颤及心房纤维化的可能机制。
方法选择38例行心脏手术的风湿性心脏病患者,按照是否合并房颤分为两组：持续性房颤组25例(AF组),其中女性14例,男性11例,年龄范围31-68岁,平均年龄(47.11±8.82)。患者的房颤持续时间为6个月～11年,平均持续时间(5.26±1.54)年。窦性心律组15例(SR)组,其中女性9例,男性6例,年龄范围33-57岁,平均年龄48.24±5.23岁。所有患者手术前均行心脏超声评价心脏结构情况；所有标本均来源于行心脏手术患者的右心耳组织。按照Trizol
步法的步骤提取右心耳组织的总RNA,采用实时荧光定量PCR法检测SIRT1mRNA在心房组织的表达；采用免疫组化法检测SIRT1蛋白、p53蛋白在心房组织的表达,采用masson染色评价心房纤维化程度。
结果判定：实时荧光定量PCR法检测SIRT1mRNA结果：用比较阈值法测定目的基因的相对表达量。SIRT1、p53免疫组化检测结判断：阳性着色定义为心房肌细胞着色部位在胞核和胞浆,以心房肌细胞核为主；阴性着色定义为心房肌细胞无明显着色,部分心房肌细胞胞浆可呈现浅棕色；蛋白表达量=胞核阳性的细胞数／细胞总数(%)(每个标本均随机选取5个高倍镜视野进行测量,取其均值)。Masson染色评价心房组织纤维化程度：采用胶原半定量分析计算胶原容积分数,该值代表心房纤维化程度。心房组织切片的光镜拍片显示正常胶原纤维为蓝色,变性胶原纤维为白色,心房肌组织为红色。应用医学图像分析系统,计算胶原容积分数-胶原纤维／视野面积(%)(每个标本均随机选取5个高倍镜视野进行测量,取其均值)。
比较两组患者SIRT1mRNA及蛋白表达情况、p53蛋白表达情况、心房纤维化程度,分析SIRT1表达与心房纤维化的关系,SIRT1表达与p53蛋白表达的关系。
结果
1.两组患者心房纤维化程度比较可见AF组纤维化程度更明显,AF组胶原容积分数明显高于SR组,差异有统计学意义(p<0.05)。
2.两组患者心房组织均可见SIRT1mRNA表达,其中AF组患者SIRT1mRNA表达高于SR组,差异有统计学意义(p<0.01)。
3.两组患者心房组织均可见SIRT1蛋白表达,其中AF组患者SIRT1蛋白表达高于SR组,差异有统计学意义,(p<0.01)。
4.两组患者心房组织均可见p53蛋白表达,其中AF组患者p53蛋白表达高于SR组,差异有统计学意义(p<0.05)
5.SIRT1表达量与心房结构的相关性分析研究：将AF组SIRT1mRNA及蛋白表达量分别与左房、右房内径行相关分析,发现SIRT1表达与心房内径无明显相关性,其相关系数分别为：r=0.198,r=0.047(左房),r=0.027,r=0.096,p均>0.05(右房)。
6.SIRT1表达量与心房纤维化的相关分析研究：将AF组SIRT1mRNA及蛋白表达量分别与心房纤维化容积分数行相关分析,发现SIRT1mRNA及蛋白表达量与心房纤维化容积分数均呈负相关,r=-0.643,r=-0.721,p均<0.05。
7.SIRT1表达量与P53相关性分析研究：将AF组SIRT1mRNA及蛋白表达量分别与p53进行相关分析,发现SIRT1mRNA及蛋白表达量与p53无明显相关性,r=0.163,r=0.069,p>0.05。
8.SIRT1表达量与房颤持续时间相关性分析：将AF组SIRT1mRNA及蛋白表达量分别与房颤持续时间行相关分析,发现SIRT1mRNA及蛋白表达量与房颤持续时间呈负相关,r=-0.749,r=-0.601,p均<0.05。
结论房颤患者心房组织SIRT1表达有所增加,随房颤持续时间的延长,SIRT1表达呈下降趋势,SIRT1表达与心房纤维化呈负相关,与p53表达无明显相关性,提示SIRT1高表达可通过抑制心房纤维化,抑制房颤的进展,该保护作用随房颤持续时间的延长而逐渐减弱。
创新点与局限性
1.本研究采用在体心房组织检测SIRT1的mRNA及蛋白表达,试验对象比较新颖。
2.本研究针对SIRT1与风湿性心脏病合并的房颤的相关性进行研究,既往未有相关报道。
3.本研究发现风湿性心脏病合并房颤患者心房组织SIRT1表达高于窦性心律患者。
4.本研究发现SIRT1表达与心房纤维化呈负相关,可抑制心房纤维化程度,并且该抑制作用随房颤持续时间的延长而减弱。
5.本研究发现SIRT1表达与p53无明显相关性。
本研究不足之处在于只对风湿性心脏病患者的SIRT1表达进行研究,结果有局限性。本研究未阐明SIRT1抑制心房纤维化的具体机制,及SIRT1与房颤关系的具体机制,可在将来的动物试验中进一步研究。
第二部分
高血压合并房颤患者外周血单个核细胞组蛋白去乙酰化酶SIRT1表达与氧化应激及炎症相关性研究
目的观察高血压合并房颤患者外周血单个核细胞SIRT1的表达情况,以及外周血氧化应激指标、hsCRP水平,了解房颤患者SIRT1表达及其与氧化应激及炎症因子的关系。
方法选择2011年1月至2011年12月住院的高血压病合并房颤患者58例作为试验组。按照房颤的类型分为两组：持续性房颤组33例(AF1组),持续性房颤指房颤持续时间超6个月,年龄范围45～83岁,平均年龄57.38±6.53岁。房颤持续时间为7个月～13年,平均时间3.58±1.07年。阵发性房颤组25例(AF2组),阵发性房颤指房颤发作呈阵发性,每次发作时间低48小时,年龄范围37～69岁,平均年龄56.35±5.68岁。对照组：选择2011年1月至2011年12月住院的高血压合并窦性心律患者30例,设为窦性心律组(SR),年龄范围35～78岁,平均年龄52.43±9.37岁。记录研究组所有患者的一般资料,包括年龄、性别、病史等情况。并分组整理。所有患者抽取静脉血,采用实时荧光定量PCR方法检测外周血单个核细胞SIRT1mRNA表达情况,用硫代巴比妥酸法测定外周血中丙二醛(MDA)含量,采用免疫比浊法测定高敏C反应蛋白(hsCRP)含量。分析SIRT1在房颤患者外周血的表达情况,及其与氧化应激指标、hsCRP的相关性。
结果
1.三组患者单个核细胞均可见SIRT1表达,其中AF2组表达高于其他两组,差异有统计学意义,p<0.01,AF1组与SR组比较有增高趋势,但差异无统计学意义。p>0.05。
2.各组氧化应激指标(MDA)结果：AF1组MDA含量高于SR组,差异有统计学意义,p<0.01,AF2组MDA含量与SR组比较无明显差异p>0.05,组间比较可见AF1组MDA含量高于AF2组,差异有统计学意义,p<0.01。
3.各组hsCRP水平比较：AF1组hsCRP含量高于SR组,差异有统计学意义,p<0.01,AF2组hsCRP含量与SR组比较有增高趋势,但无统计学意义,p>0.05,组间比较可见AF1组hsCRP含量高于AF2组,差异有统计学意义,p<0.01。
4.各组SIRT1表达与MDA相关性分析结果显示：AF1组SIRT1表达与MDA呈负相关,相关系数为rs=-0.416,p<0.05。AF2组SIRT1表达与MDA呈负相关性,相关系数为rs=-0.641, p<0.01。SR组SIRT1表达与MDA无相关性,相关系数为r=0.034,p>0.05。
5.各组SIRT1表达与hsCPR相关性分析结果显示：AF1组SIRT1表达与hsCPR无相关性,相关系数为rs=0.027,p>0.05。AF2组SIRT1表达与hsCPR无相关性,相关系数为0.004,P>0.05。SR组SIRT1表达与hsCPR无相关性,相关系数分别为rs=0.007,p>0.05。
6.SIRT1表达与房颤持续时间相关性分析：将AF1组SIRT1表达量与房颤持续时间行相关性分析,结果显示SIRT1表达量与房颤持续时间呈负相关,rs=-0.834,p<0.01。
结论高血压合并房颤患者外周血单个核细胞可见SIRT1表达增加,其中阵发性房颤患者增加明显,持续性房颤患者有增加趋势,而且随房颤持续时间的延长逐渐下降,SIRT1表达与外周血氧化应激水平呈负相关,与hsCRP无明显相关性,提示SIRT1可通过抑制氧化应激抑制房颤的进展,在房颤中起作用。
创新点及局限性
1.本研究主要检测高血压患者外周血单个核细胞中SIRT1的mRNA表达,研究对象有创新性。
2.本研究针对SIRT1与高血压合并的房颤的相关性进行研究,既往未有相关报道。
3.本研究发现高血压合并房颤外周血单个核细胞SIRT1表达高于窦性心律患者,特别是阵发性房颤的患者。
4.本研究发现SIRT1表达与氧化应激程度呈负相关,可抑制氧化应激程度,并且该抑制作用随房颤持续时间的延长而减弱。
5.本研究发现SIRT1表达与hsCRP无明显相关性。
本研究不足之处在于未对SIRT1在房颤中的具体作用机制做更加深入的研究,结果有局限性。
Part Ⅰ
Expression of histone deacetylases SIRT1and relationship between SIRT1and atrial fibrosis in atrial fibrillation of rheumatic heart disease
Objective To observe the expression of SIRT1, p53and find the relationship between SIRT1, p53and atrial fibrosis in atrial fibrillation of rheumatic heart disease, then find the mechanism of SIRT1in atrial fibrillation.
Methods38patients with rheumatic heart disease were taken as the study group,they were divided into two groups:AF group (atrial fibrillation, n=25) with atrial fibrillation longer than six months and SR group (sinus rhythm, n=13). The right atrial appendage tissue was obtained during heart valvular surgery. The expression of SIRT1in atrial tissue was detected by real-time quantitative PCR and immunohistochemical assay,the expression of SIRT1and p53protein were detected by immunohistochemical assay,the atrial fibrosis was identified by masson staining,the cardiac structure was measured by the transthoracic echocardiography.
Results Compared with the SR group, the atrial fibrosis was more serious and the cardiac volume factor was higher in the AF group (P<0.05),the expression of SIRT1mRNA in the atrium was significantly increased in AF groups (P<0.01),the expression of SIRT1protein in the atrium was significantly increased in AF groups (P<0.01). Compared with the SR group,the expression of p53protein in the atrium was also significantly increased in AF groups (P<0.05). Linear correlation revealed that SIRT1mRNA and protein had negative correlation with atrial fibrosis, p<0.05. Linear correlation revealed that p53expression had no correlation with SIRT1, p>0.05. Linear correlation revealed that SIRT1expression had no correlation with atrial dimension, p>0.05. Linear correlation also revealed that SIRT1mRNA and protein had negative correlation with the duration of AF(P <0.05).
Conclusion SIRT1expression was found increasing in atrial fibrillation SIRT1maybe effect the atrial fibrillation to inhibit the atrial fibrosis.
Innovations and limitations
SIRT1mRNA and protein expression were tested in body atrial tissue for the first time in this study;This is also the first study to detect the relationship between SIRT1and atrial fibrillation of rheumatic heart disease.We found that SIRT1expression of patient with atrial fibrillation was more increased than that of patients with sinus rhythm for the first time;We also found that SIRT1expression and atrial fibrosis was negatively correlated, SIRT1could inhibit atrial fibrosis, and the inhibition was negatively correlated with the duration of atrial fibrillation for the first time.This is the first time that we found that SIRT1expression and p53had no significant correlation.
This study was only including the patients with rheumatic heart disease, the results were limited.
Part Ⅱ
Expression of histone deacetylases SIRT1in the peripheral blood mononuclear cells and relationship between SIRT1,Oxidative Stress and inflammation in atrial fibrillation with hypertienson
Objective To observe the expression of SIRT1in the peripheral blood mononuclear cells and relationship between SIRT1、Oxidative Stress and inflammation in atrial fibrillation with hypertension.
Methods58patients with atrial fibrillation and hypertention were taken as the study group,they were divided into two groups:the AF1group(with persistent atiral fibrillation,n=33)、the AF2group(with paroxysmal atiral fibrillation,n=25).Another30patients without atrial fibrillation were the SR group(with sinus rhythm n=30).All the patients should note age, gender, smoking history and so on.The blood sample was took the next morning after hospitaled.The expression of SIRT1protein in the peripheral mononuclear cells was measured using realtime PCR, and Oxidative Stress was estimated by MDA, inflammation was estimated by hs-CRP of the blood sample.
Results SIRT1expression was found in the three groups,compared with the SR groups, the expression of SIRT1mRNA in the leukomonocyte of the blood sample was significantly increased in the AF2groups (P<0.01),.however the expression of SIRT1mRNA was not higher in the AF1groups (P>0.05), compared with the AF1groups, the expression of SIRT1was significantly increased in the AF2groups (P<0.01).Compared with the SR groups,the MDA of the blood sample was significantly increased in the AF1groups (P<0.01),.however not higher in the AF2groups (P>0.05), compared with the AF2groups, the MDA was significantly increased in the AF1groups (P<0.01).Compared with the SR groups,the hs-CRP of blood sample was significantly increased in the AF1groups (P<0.01),.however not higher in the AF2groups (P>0.05), compared with the AF2groups, the hs-CRP was significantly increased in the AF1groups (P<0.01).linear correlation revealed that SIRT1expression had significantly negative correlation with MDA,p<0.05,and linear correlation revealed that SIRT1expression had no correlation with hs-CRP(P>0.05). Linear correlation also revealed that SIRT1mRNA and protein had negative correlation with the duration of AF(P<0.01).
Conclusion SIRT1expression was found increasing in paroxysmal atrial fibrillation with hypertention, SIRT1could inhibit the Oxidative Stress and effect the atrial fibrillation.
Innovations and limitations
SIRT1mRNA expression was tested in human peripheral blood cells for the first time in this study;This is also the first study to detect the relationship between SIRT1and atrial fibrillation of hypertension.We found that SIRT1expression of patient with atrial fibrillation was more increased than that of patients with sinus rhythm for the first time especially the patients with paroxysmal atrial fibrillation;We also found that SIRT1expression and oxidative stress was negatively correlated, SIRT1could inhibit oxidative stress, and the inhibition was negatively correlated with the duration of atrial fibrillation for the first time.This is the first time that we found that SIRT1expression and hsCRP had no significant correlation.
This study was not including the deeper mechanism of SIRT1with atrial fibrillation,the results were limited.
风湿性心脏病合并房颤患者心房组织组蛋白去乙酰化酶SIRT1表达与心房纤维化的相关性研究
目的通过观察房颤患者心房肌组织SIRT1的表达情况、心房肌纤维化的程度,SIRT1与心房纤维化的相关关系,了解房颤患者心房肌组织SIRT1的表达及其与心房纤维化的相关性,并通过检测心房肌组织p53蛋白的表达情况,了解房颤患者心房肌组织SIRT1表达参与房颤及心房纤维化的可能机制。
方法选择38例行心脏手术的风湿性心脏病患者,按照是否合并房颤分为两组：持续性房颤组25例(AF组),其中女性14例,男性11例,年龄范围31-68岁,平均年龄(47.11±8.82)。患者的房颤持续时间为6个月～11年,平均持续时间(5.26±1.54)年。窦性心律组15例(SR)组,其中女性9例,男性6例,年龄范围33-57岁,平均年龄48.24±5.23岁。所有患者手术前均行心脏超声评价心脏结构情况；所有标本均来源于行心脏手术患者的右心耳组织。按照Trizol
步法的步骤提取右心耳组织的总RNA,采用实时荧光定量PCR法检测SIRT1mRNA在心房组织的表达；采用免疫组化法检测SIRT1蛋白、p53蛋白在心房组织的表达,采用masson染色评价心房纤维化程度。
结果判定：实时荧光定量PCR法检测SIRT1mRNA结果：用比较阈值法测定目的基因的相对表达量。SIRT1、p53免疫组化检测结判断：阳性着色定义为心房肌细胞着色部位在胞核和胞浆,以心房肌细胞核为主；阴性着色定义为心房肌细胞无明显着色,部分心房肌细胞胞浆可呈现浅棕色；蛋白表达量=胞核阳性的细胞数／细胞总数(%)(每个标本均随机选取5个高倍镜视野进行测量,取其均值)。Masson染色评价心房组织纤维化程度：采用胶原半定量分析计算胶原容积分数,该值代表心房纤维化程度。心房组织切片的光镜拍片显示正常胶原纤维为蓝色,变性胶原纤维为白色,心房肌组织为红色。应用医学图像分析系统,计算胶原容积分数-胶原纤维／视野面积(%)(每个标本均随机选取5个高倍镜视野进行测量,取其均值)。
比较两组患者SIRT1mRNA及蛋白表达情况、p53蛋白表达情况、心房纤维化程度,分析SIRT1表达与心房纤维化的关系,SIRT1表达与p53蛋白表达的关系。
结果
1.两组患者心房纤维化程度比较可见AF组纤维化程度更明显,AF组胶原容积分数明显高于SR组,差异有统计学意义(p<0.05)。
2.两组患者心房组织均可见SIRT1mRNA表达,其中AF组患者SIRT1mRNA表达高于SR组,差异有统计学意义(p<0.01)。
3.两组患者心房组织均可见SIRT1蛋白表达,其中AF组患者SIRT1蛋白表达高于SR组,差异有统计学意义,(p<0.01)。
4.两组患者心房组织均可见p53蛋白表达,其中AF组患者p53蛋白表达高于SR组,差异有统计学意义(p<0.05)
5.SIRT1表达量与心房结构的相关性分析研究：将AF组SIRT1mRNA及蛋白表达量分别与左房、右房内径行相关分析,发现SIRT1表达与心房内径无明显相关性,其相关系数分别为：r=0.198,r=0.047(左房),r=0.027,r=0.096,p均>0.05(右房)。
6.SIRT1表达量与心房纤维化的相关分析研究：将AF组SIRT1mRNA及蛋白表达量分别与心房纤维化容积分数行相关分析,发现SIRT1mRNA及蛋白表达量与心房纤维化容积分数均呈负相关,r=-0.643,r=-0.721,p均<0.05。
7.SIRT1表达量与P53相关性分析研究：将AF组SIRT1mRNA及蛋白表达量分别与p53进行相关分析,发现SIRT1mRNA及蛋白表达量与p53无明显相关性,r=0.163,r=0.069,p>0.05。
8.SIRT1表达量与房颤持续时间相关性分析：将AF组SIRT1mRNA及蛋白表达量分别与房颤持续时间行相关分析,发现SIRT1mRNA及蛋白表达量与房颤持续时间呈负相关,r=-0.749,r=-0.601,p均<0.05。
结论房颤患者心房组织SIRT1表达有所增加,随房颤持续时间的延长,SIRT1表达呈下降趋势,SIRT1表达与心房纤维化呈负相关,与p53表达无明显相关性,提示SIRT1高表达可通过抑制心房纤维化,抑制房颤的进展,该保护作用随房颤持续时间的延长而逐渐减弱。
创新点与局限性
1.本研究采用在体心房组织检测SIRT1的mRNA及蛋白表达,试验对象比较新颖。
2.本研究针对SIRT1与风湿性心脏病合并的房颤的相关性进行研究,既往未有相关报道。
3.本研究发现风湿性心脏病合并房颤患者心房组织SIRT1表达高于窦性心律患者。
4.本研究发现SIRT1表达与心房纤维化呈负相关,可抑制心房纤维化程度,并且该抑制作用随房颤持续时间的延长而减弱。
5.本研究发现SIRT1表达与p53无明显相关性。
本研究不足之处在于只对风湿性心脏病患者的SIRT1表达进行研究,结果有局限性。本研究未阐明SIRT1抑制心房纤维化的具体机制,及SIRT1与房颤关系的具体机制,可在将来的动物试验中进一步研究。
第二部分
高血压合并房颤患者外周血单个核细胞组蛋白去乙酰化酶SIRT1表达与氧化应激及炎症相关性研究
目的观察高血压合并房颤患者外周血单个核细胞SIRT1的表达情况,以及外周血氧化应激指标、hsCRP水平,了解房颤患者SIRT1表达及其与氧化应激及炎症因子的关系。
方法选择2011年1月至2011年12月住院的高血压病合并房颤患者58例作为试验组。按照房颤的类型分为两组：持续性房颤组33例(AF1组),持续性房颤指房颤持续时间超6个月,年龄范围45～83岁,平均年龄57.38±6.53岁。房颤持续时间为7个月～13年,平均时间3.58±1.07年。阵发性房颤组25例(AF2组),阵发性房颤指房颤发作呈阵发性,每次发作时间低48小时,年龄范围37～69岁,平均年龄56.35±5.68岁。对照组：选择2011年1月至2011年12月住院的高血压合并窦性心律患者30例,设为窦性心律组(SR),年龄范围35～78岁,平均年龄52.43±9.37岁。记录研究组所有患者的一般资料,包括年龄、性别、病史等情况。并分组整理。所有患者抽取静脉血,采用实时荧光定量PCR方法检测外周血单个核细胞SIRT1mRNA表达情况,用硫代巴比妥酸法测定外周血中丙二醛(MDA)含量,采用免疫比浊法测定高敏C反应蛋白(hsCRP)含量。分析SIRT1在房颤患者外周血的表达情况,及其与氧化应激指标、hsCRP的相关性。
结果
1.三组患者单个核细胞均可见SIRT1表达,其中AF2组表达高于其他两组,差异有统计学意义,p<0.01,AF1组与SR组比较有增高趋势,但差异无统计学意义。p>0.05。
2.各组氧化应激指标(MDA)结果：AF1组MDA含量高于SR组,差异有统计学意义,p<0.01,AF2组MDA含量与SR组比较无明显差异p>0.05,组间比较可见AF1组MDA含量高于AF2组,差异有统计学意义,p<0.01。
3.各组hsCRP水平比较：AF1组hsCRP含量高于SR组,差异有统计学意义,p<0.01,AF2组hsCRP含量与SR组比较有增高趋势,但无统计学意义,p>0.05,组间比较可见AF1组hsCRP含量高于AF2组,差异有统计学意义,p<0.01。
4.各组SIRT1表达与MDA相关性分析结果显示：AF1组SIRT1表达与MDA呈负相关,相关系数为rs=-0.416,p<0.05。AF2组SIRT1表达与MDA呈负相关性,相关系数为rs=-0.641, p<0.01。SR组SIRT1表达与MDA无相关性,相关系数为r=0.034,p>0.05。
5.各组SIRT1表达与hsCPR相关性分析结果显示：AF1组SIRT1表达与hsCPR无相关性,相关系数为rs=0.027,p>0.05。AF2组SIRT1表达与hsCPR无相关性,相关系数为0.004,P>0.05。SR组SIRT1表达与hsCPR无相关性,相关系数分别为rs=0.007,p>0.05。
6.SIRT1表达与房颤持续时间相关性分析：将AF1组SIRT1表达量与房颤持续时间行相关性分析,结果显示SIRT1表达量与房颤持续时间呈负相关,rs=-0.834,p<0.01。
结论高血压合并房颤患者外周血单个核细胞可见SIRT1表达增加,其中阵发性房颤患者增加明显,持续性房颤患者有增加趋势,而且随房颤持续时间的延长逐渐下降,SIRT1表达与外周血氧化应激水平呈负相关,与hsCRP无明显相关性,提示SIRT1可通过抑制氧化应激抑制房颤的进展,在房颤中起作用。
创新点及局限性
1.本研究主要检测高血压患者外周血单个核细胞中SIRT1的mRNA表达,研究对象有创新性。
2.本研究针对SIRT1与高血压合并的房颤的相关性进行研究,既往未有相关报道。
3.本研究发现高血压合并房颤外周血单个核细胞SIRT1表达高于窦性心律患者,特别是阵发性房颤的患者。
4.本研究发现SIRT1表达与氧化应激程度呈负相关,可抑制氧化应激程度,并且该抑制作用随房颤持续时间的延长而减弱。
5.本研究发现SIRT1表达与hsCRP无明显相关性。
本研究不足之处在于未对SIRT1在房颤中的具体作用机制做更加深入的研究,结果有局限性。
Part Ⅰ
Expression of histone deacetylases SIRT1and relationship between SIRT1and atrial fibrosis in atrial fibrillation of rheumatic heart disease
Objective To observe the expression of SIRT1, p53and find the relationship between SIRT1, p53and atrial fibrosis in atrial fibrillation of rheumatic heart disease, then find the mechanism of SIRT1in atrial fibrillation.
Methods38patients with rheumatic heart disease were taken as the study group,they were divided into two groups:AF group (atrial fibrillation, n=25) with atrial fibrillation longer than six months and SR group (sinus rhythm, n=13). The right atrial appendage tissue was obtained during heart valvular surgery. The expression of SIRT1in atrial tissue was detected by real-time quantitative PCR and immunohistochemical assay,the expression of SIRT1and p53protein were detected by immunohistochemical assay,the atrial fibrosis was identified by masson staining,the cardiac structure was measured by the transthoracic echocardiography.
Results Compared with the SR group, the atrial fibrosis was more serious and the cardiac volume factor was higher in the AF group (P<0.05),the expression of SIRT1mRNA in the atrium was significantly increased in AF groups (P<0.01),the expression of SIRT1protein in the atrium was significantly increased in AF groups (P<0.01). Compared with the SR group,the expression of p53protein in the atrium was also significantly increased in AF groups (P<0.05). Linear correlation revealed that SIRT1mRNA and protein had negative correlation with atrial fibrosis, p<0.05. Linear correlation revealed that p53expression had no correlation with SIRT1, p>0.05. Linear correlation revealed that SIRT1expression had no correlation with atrial dimension, p>0.05. Linear correlation also revealed that SIRT1mRNA and protein had negative correlation with the duration of AF(P <0.05).
Conclusion SIRT1expression was found increasing in atrial fibrillation SIRT1maybe effect the atrial fibrillation to inhibit the atrial fibrosis.
Innovations and limitations
SIRT1mRNA and protein expression were tested in body atrial tissue for the first time in this study;This is also the first study to detect the relationship between SIRT1and atrial fibrillation of rheumatic heart disease.We found that SIRT1expression of patient with atrial fibrillation was more increased than that of patients with sinus rhythm for the first time;We also found that SIRT1expression and atrial fibrosis was negatively correlated, SIRT1could inhibit atrial fibrosis, and the inhibition was negatively correlated with the duration of atrial fibrillation for the first time.This is the first time that we found that SIRT1expression and p53had no significant correlation.
This study was only including the patients with rheumatic heart disease, the results were limited.
Part Ⅱ
Expression of histone deacetylases SIRT1in the peripheral blood mononuclear cells and relationship between SIRT1,Oxidative Stress and inflammation in atrial fibrillation with hypertienson
Objective To observe the expression of SIRT1in the peripheral blood mononuclear cells and relationship between SIRT1、Oxidative Stress and inflammation in atrial fibrillation with hypertension.
Methods58patients with atrial fibrillation and hypertention were taken as the study group,they were divided into two groups:the AF1group(with persistent atiral fibrillation,n=33)、the AF2group(with paroxysmal atiral fibrillation,n=25).Another30patients without atrial fibrillation were the SR group(with sinus rhythm n=30).All the patients should note age, gender, smoking history and so on.The blood sample was took the next morning after hospitaled.The expression of SIRT1protein in the peripheral mononuclear cells was measured using realtime PCR, and Oxidative Stress was estimated by MDA, inflammation was estimated by hs-CRP of the blood sample.
Results SIRT1expression was found in the three groups,compared with the SR groups, the expression of SIRT1mRNA in the leukomonocyte of the blood sample was significantly increased in the AF2groups (P<0.01),.however the expression of SIRT1mRNA was not higher in the AF1groups (P>0.05), compared with the AF1groups, the expression of SIRT1was significantly increased in the AF2groups (P<0.01).Compared with the SR groups,the MDA of the blood sample was significantly increased in the AF1groups (P<0.01),.however not higher in the AF2groups (P>0.05), compared with the AF2groups, the MDA was significantly increased in the AF1groups (P<0.01).Compared with the SR groups,the hs-CRP of blood sample was significantly increased in the AF1groups (P<0.01),.however not higher in the AF2groups (P>0.05), compared with the AF2groups, the hs-CRP was significantly increased in the AF1groups (P<0.01).linear correlation revealed that SIRT1expression had significantly negative correlation with MDA,p<0.05,and linear correlation revealed that SIRT1expression had no correlation with hs-CRP(P>0.05). Linear correlation also revealed that SIRT1mRNA and protein had negative correlation with the duration of AF(P<0.01).
Conclusion SIRT1expression was found increasing in paroxysmal atrial fibrillation with hypertention, SIRT1could inhibit the Oxidative Stress and effect the atrial fibrillation.
Innovations and limitations
SIRT1mRNA expression was tested in human peripheral blood cells for the first time in this study;This is also the first study to detect the relationship between SIRT1and atrial fibrillation of hypertension.We found that SIRT1expression of patient with atrial fibrillation was more increased than that of patients with sinus rhythm for the first time especially the patients with paroxysmal atrial fibrillation;We also found that SIRT1expression and oxidative stress was negatively correlated, SIRT1could inhibit oxidative stress, and the inhibition was negatively correlated with the duration of atrial fibrillation for the first time.This is the first time that we found that SIRT1expression and hsCRP had no significant correlation.
This study was not including the deeper mechanism of SIRT1with atrial fibrillation,the results were limited.
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