FrzA基因转导干预缺血性心力衰竭小鼠心肌Wnt信号通路的研究

目的:研究重组9型腺相关病毒(recombinant adeno-associated virus serotype 9,rAAV9)携带FrzA基因转导干预缺血性心衰小鼠心肌Wnt信号通路的可行性,为基因治疗心力衰竭提供新的思路.方法:选择3月龄雄性C57BL/6J小鼠共130只,随机分为空白组(n=10),心衰组(n=40),心衰+空病毒(rAAV9-GFP)注射组(n=40),心衰+rAAV9-FrzA组(n=40),采用结扎左冠状动脉定量控制心梗面积,于术后2周行心脏超声评各组心功能变化,再经尾静脉注射已稀释好的病毒,28d后处死小鼠取心脏标本,RT-PCR检测心肌目的基因FrzA以及Dvl-1,β-catenin的表达;Western blot检测心肌Wnt信号通路关键分子Dvl-1,GSK3β,p-GSK3β,β-catenin的表达.结果:与空白组相比,成功建立心衰模型后小鼠心功能均不同程度降低(P＜0.05);FrzA组与心衰组相比,心功能明显改善(P＜0.05);经尾静脉注射可成功将rAAV9-FrzA导入小鼠体内,并且目的基因FrzA在心肌组织中高表达(P＜0.05);心衰小鼠心肌中Wnt信号通路关键分子Dvl-1,p-GSK3β,β-catenin的表达显著升高(P＜0.05),FrzA转导后小鼠心肌中Wnt信号通路中关键分子Dvl-1,p-GSK3β,β-catenin表达均降低(P＜0.05)结论:利用rAAV9-FrzA转导缺血性心衰小鼠可以有效的干预心肌Wnt信号通路,抑制其活性,为基因治疗缺血性心衰提供了新的思路.     

高龄老年心力衰竭患者临床特点分析

目的：通过对不同年龄组心力衰竭常见临床表现进行对比分析,寻找出老年心力衰竭的特点,为临床诊断和治疗老年特别是高龄老年（〉80岁）心力衰竭提供依据。方法：我院专职人员采取回顾性调查方法,记录所选病例相关的数据：一般临床资料、基础心脏疾病、诱发因素、伴随疾病、临床表现、相关实验室检验检查情况、药物治疗具体种类、转归情况等;根据年龄分为3组：246例60—69岁组,平均年龄（64．28±3．0）2V;215例70-79岁组,平均年龄（74．19±2．85）岁;71例〉80岁组,平均年龄（84±3．34）岁。运用计算机软件Excel建立老年心衰患者资料数据库,SPSS13．0for：windows软件包进行统计分析。结果：1）随着年龄增加,心衰典型的临床表现减少,特别是高龄心衰患者,其临床表现极不典型,心力衰竭程度较重,容易在短期内出现重要器官的严重并发症;2）高龄老年人心衰以冠心病、高血压病为主要病因,随年龄增加,多病因心衰比例在上升;3）我院高龄老年人心衰的治疗以利尿剂、洋地黄类、硝酸醋类药物为主。结论：高龄老年人心力衰竭具有明确病因、程度重,症状不典型,具有严重并发症,治疗相对规范的临床特点。     

美托洛尔联合硝酸甘油治疗老年高血压伴左心衰的临床分析

目的：观察美托洛尔联合硝酸甘油治疗老年高血压伴左心衰的临床疗效及其对血管内皮生长因子（VEGF）,高敏C反应蛋白（hs-CRP）和脑钠素（BNP）的影响。方法：选取2009年6月至2010年12月入住我院的高血压伴急性左心衰患者150例,将其随机分为观察组和对照组,每组各75例。对照组在强心,利尿的基础上予以硝酸甘油治疗;观察组在对照组的基础上予以美托洛尔治疗。观察两组的疗效,血压,心率,血氧饱和度,血浆VEGF,hs-CRP和BNP的表达。结果：观察组的总有效率为94.67%,而对照组的总有效率为80.00%,观察组的总有效率明显高于对照组（P〈0.05）。两组治疗后,收缩压,舒张压,心率,VEGF,hs-CRP和BNP均较治疗前明显降低（P〈0.01）,观察组的降低水平较对照组更为明显（P〈0.01）;而两组治疗后的血氧饱和度较治疗前明显提高,观察组的提高水平更为明显（P〈0.01）。结论：美托洛尔联合硝酸甘油治疗老年高血压伴左心衰疗效显著,其机理可能与降低血浆中的VEGF,hs-CRP和BNP水平有关。     

肺炎合并心力衰竭患者血浆BNP,cTn1的变化及其临床意义

目的:探讨血浆脑钠肽(BNP)和心肌肌钙蛋白(cTn1)在肺炎合并心力衰竭患者血浆脑钠肽(BNP)和心肌肌钙蛋白(cTn1)的变化情况及、肺炎未合并心衰患者及健康对照组中的不同表达,探讨血浆脑钠肽(BNP)和心肌肌钙蛋白(cTn1)与疾病变化的关系及在肺炎合并心力衰竭中的临床诊断的意义.方法:回顾性分析我院自2010年1月至2012年1月收治的42例肺炎合并心衰患者,同期收治的肺炎末合并心衰患者34例为阳性对照组,以及同期在门诊进行体检的30例健康患者为阴性对照组.在入院后24h之内评估心脏功能并检测血浆BNP及cTn1水平变化,以及心衰合并肺炎患者入院24h急性期及心衰恢复期BNP和cTn1水平的变化,比较BNP和cTn1在的不同表达.结果:心衰组、阳性对照组、阴性对照组患者BNP(378.14,142.53,0.74±0.15)和cTn1 (0.84,0.32,0.18)比较,在统计学上具有显著性意义(H=140.67,H=30.14,P＜0.001).心衰急性期与心衰恢复期BNP(378.14,140.32)和cTn1(0.84,0.04)水平比较,在统计学上具有显著性差异(t=2.044,t=2.051,P＜ 0.05).结论:BNP与cTn1在肺炎合并心衰患者为高表达,显著高于肺炎未合并心衰患者,合并心衰与未合并心衰组的BNP与cTn1水平也显著高于健康对照组,表明BNP与cTn1的表达与病情呈正相关.且在肺炎合并心衰急性期的表达高于恢复期,表明BNP、cTnⅠ水平变化可为诊断患者病情严重程度及肺炎合并心衰为急性期或慢性提高依据,可以为早期心功能衰竭提高临床参考.     

REPEATED ASSESSMENT OF THE ENDOGENOUS 24-HOUR PROFILE OF BLOOD PRESSURE UNDER CONSTANT ROUTINE*

The impact of environmental and behavioral factors on the 24-h profile of blood pressure (BP) has been well established. Various attempts have been made to control these exogenous factors, in order to investigate a possible endogenous circadian variation of BP. Recently, we reported the results of the first environmentally and behaviorally controlled laboratory study with 24-h recordings of BP and heart rate (HR) during maintained wakefulness. In this constant-routine study, a pronounced endogenous circadian rhythm of HR was found, but circadian variation of BP was absent. This result suggested that the circadian rhythm of BP observed in earlier controlled studies, with sleep allowed, was evoked by the sleep–wake cycle as opposed to the endogenous circadian pacemaker. In order to verify our previous finding during maintained wakefulness, we repeated the experiment five times with six normotensive, healthy young subjects. Statistical analyses of the hourly measurements of BP and HR confirmed the replicable presence of an endogenous circadian rhythm of HR, as well as the consistent absence of an endogenous circadian variation of BP. Thus, this study provided additional evidence that the 24-h profile of BP—as observed under normal circumstances—is the sole result of environmental and behavioral factors such as the occurrence of sleep, and has no endogenous circadian component. (Chronobiology International, 18(1), 85–98, 2001)     

Circadian Rhythm of Blood Pressure and Heart Rate in Healthy Persons and Kidney Transplant Patients: Correlations with Activity

Fourteen diurnally active (07: 00–22: 39 h) normotensive healthy control subjects and 14 kidney transplant patients were studied by ambulatory blood pressure monitoring and wrist actigraphy simultaneously during one 24-h period. In the control group, circadian rhythms in systolic (SBP), diastolic (DBP), and mean arterial (MAP) blood pressure, heart rate (HR), and wrist activity were documented by cosinor analysis with comparable afternoon peak times. In contrast, circadian rhythms with afternoon acrophases were detected only in HR and wrist activity in the patient group. The correlation of wrist activity with HR in controls and patients was comparable. Wrist activity and blood pressure were associated (r = 0.65 DBP and 0.54 SBP; p < 0.05) in controls, while in patients the relationship was weak or absent (r ranging from 0.02 SBP to 0.22 DBP). In 6 of 14 patients, BP and wrist activity were negatively correlated, reflecting the existence of nocturnal hypertension. In eight others, the correlation was small but positive. The 24-h pattern in BP and wrist activity in controls was comparably phased; however, this was not the case for the transplant patients, indicating the day-night pattern in blood pressure in this group is strongly dependent on pathologic phenomena rather than activity level and pattern.     

Long-Term Heart Rate Fluctuations in Postoperative and Brain-Dead Patients

Long-term heart rate fluctuations in postoperative and brain-dead patients were investigated. Heart rates were monitored continuously, and the data were stored, edited, and interpolated to allow for data lost during calibration and disconnection of the sensors for various treatments. Heart rate power spectra were calculated using the fast Fourier transform method. The power spectra of the patients who recovered showed that the heart rate fluctuated and produced a 1/f relationship, termed 1/f fluctuations, whereas those of patients who died in the intensive care unit (ICU) consisted of white-noise-like signals. The power spectra in brain-dead patients showed a 1/f relationship under steady-state conditions, while the power density and variation of the frequency distribution were lower than those in a normal subject. Therefore, 1/f fluctuations appear to be universal and occur independent of the central nervous system. (Chronobiology International, 15(6), 633-646, 1998)     

CIRCADIAN PATTERN OF BLOOD PRESSURE,HEART RATE,AND DOUBLE PRODUCT IN LIVER GLYCOGEN STORAGE DISEASE

The objective of this study was to determine systolic, diastolic, and mean arterial blood pressure (SBP, DBP, and MAP), heart rate (HR), double-product (DP: SBP×HR), and activity levels and their 24h pattern in liver glycogen storage disease (LGSD) patients. A case series of 12 (11 pediatric and one adult) diurnally active LGSD (seven type I, three type III, and two type IX) subjects were simultaneously assessed by 24h ambulatory blood pressure monitoring and wrist actigraphy. Nine subjects were judged to be hypertensive based on the criterion of an elevated 24h mean SBP and/or DBP being elevated beyond reference standards or the SBP and/or DBP load (percentage of time BP exceeds normal values) being greater than 25%. Two of the three other subjects, not viewed as hypertensive based on their 24h average SBP or DBP, exhibited daytime or nighttime SBP and/or DBP load hypertension. Each study variables displayed statistically significant (p<0.001) group circadian rhythmicity. The SBP, DBP, and MAP displayed comparable 24h patterns of appreciable amplitude (total peak–trough variation equal to 17.7, 23.6, and 19.6%, respectively, of the 24h mean) with highest values (orthophase) occurring ～11 h after the commencement of daytime activity. The sleep-time trough (bathyphase) occurred ～4.5 h before morning awakening. The statistically significant (p<0.006) circadian rhythms of HR (amplitude equal to 33.2% of the 24h mean) and DP (amplitude equal to 49.4% of the 24h mean) peaked earlier, ～7.4 h into the daytime activity span. The sleep-time trough occurred ～3 h before morning awakening. The 24h pattern in the cardiovascular variables was correlated with the 24h pattern of activity, with r ranging from 0.50 for DBP to 0.39 for HR.