针刺对慢性情绪应激焦虑大鼠血浆ANP、CORT和肾上腺ANP受体的影响

目的:通过观察针刺对慢性情绪应激焦虑大鼠血浆心房利钠肽(atrial natriuretic peptide,ANP)、皮质酮(corticosterone,CORT)含量和肾上腺利钠肽A型受体(natriuretic peptide receptor type A,NPR-A)水平的影响,探讨针刺干预焦虑障碍模型的部分外周作用机理。方法:选取清洁级雄性SD大鼠30只,完全随机分为空白组、模型组、针刺组3组。运用不可预知的慢性情绪应激法建立焦虑动物模型,针刺组同时选取"内关""神门"予以治疗。以高架十字迷宫实验(elevated plus maze test,EPM)测试大鼠焦虑样行为,分别采用放射免疫法和ELISA法检测血浆ANP和CORT的含量,运用免疫组化法检测肾上腺皮质部NPR-A的水平。结果:与空白组对比,模型组的进入开臂次数(open-arms entries,OE)占入臂总次数的百分比值(OE%)显著下降(P0.01),血浆ANP、CORT值均明显升高(P0.05或P0.01);与模型组相比,针刺组OE%值有升高并接近空白组,血浆CORT显著下降(P0.01);3组肾上腺皮质NPR-A水平无显著性差异。结论:针刺可能通过降低血浆ANP和CORT的含量达到改善焦虑情绪的目的,而肾上腺皮质ANP受体的参与作用未显现。     

Developmental programing of thirst and sodium appetite

Thirst and sodium appetite are the sensations responsible for the motivated behaviors of water and salt intake, respectively, and both are essential responses for the maintenance of hydromineral homeostasis in animals. These sensations and their related behaviors develop very early in the postnatal period in animals. Many studies have demonstrated several pre- and postnatal stimuli that are responsible for the developmental programing of thirst and sodium appetite and, consequently, the pattern of water and salt intake in adulthood in need-free or need-induced conditions. The literature systematically reports the involvement of dietary changes, hydromineral and cardiovascular challenges, renin–angiotensin system and steroid hormone disturbances, and lifestyle in these developmental factors. Therefore, this review will address how pre- and postnatal challenges can program lifelong thirst and sodium appetite in animals and humans, as well as which neuroendocrine substrates are involved. In addition, the possible epigenetic molecular mechanisms responsible for the developmental programing of drinking behavior, the clinical implications of hydromineral disturbances during pre- and postnatal periods, and the developmental origins of adult hydromineral behavior will be discussed.     

Natriuretic peptides

Natriuretic peptides (NPs) are released from the heart in response to pressure and volume overload. B-type natriuretic peptide (BNP) and N-terminal-proBNP have become important diagnostic tools for assessing patients who present acutely with dyspnea. The NP level reflects a compilation of systolic and diastolic function as well as right ventricular and valvular function. Studies suggest that using NPs in the emergency department can reduce the consumption of hospital resources and can lower costs by either eliminating the need for other, more expensive tests or by establishing an alternative diagnosis that does not require hospital stay. Caveats such as body mass index and renal function must be taken into account when analyzing NP levels. Natriuretic peptide levels have important prognostic value in multiple clinical settings, including in patients with stable coronary artery disease and with acute coronary syndromes. In patients with decompensated heart failure due to volume overload, a treatment-induced drop in wedge pressure is often accompanied by a rapid drop in NP levels. Knowing a patient's NP levels might thus assist with hemodynamic assessment and subsequent treatment titration. Monitoring NP levels in the outpatient setting might also improve patient care and outcomes.     

利钾尿肽与心钠素摩尔比在阵发心房纤颤时的作用

目的：探讨利钾尿肽（KP）及KP与心钠素（ANP）摩尔比在阵发心房纤颤时的意义。方法：用放射免疫分析法测定23例阵发房颤患者血浆中KP与ANP的水平，并以正常人对照， 结果：房颤患者血浆中KP与ANP的水平明显高于对照组（P＜0．01），而血浆中KP／ANP摩尔比显著低于正常对照组（P＜0．01）。结论：KP含量与ANP的比例关系的变化在阵发房颤的发病中起一定的作用。     

Effects of nocturnal noninvasive mechanical ventilation on heart rate variability of patients with advanced COPD

BACKGROUND: Cardiovascular comorbidities have a negative impact on the health status and prognosis of patients with COPD. We determined whether nocturnal noninvasive (positive) mechanical ventilation (NIMV) can improve heart rate variability (HRV), decrease circulating natriuretic peptide levels, and improve functional performance of patients with very advanced COPD. METHODS: A randomized, double-blind, parallel controlled trial was conducted in 23 participants with stable but advanced COPD. Participants received standard medical therapy plus nocturnal NIMV or standard medical therapy plus sham NIMV for 3 months. RESULTS: After 3 months of NIMV therapy, the 24-h triangular interpolation of N-N intervals increased from 322 to 473 ms (p = 0.034), the 24-h HRV index (HRVI) increased from 21.8 to 29.9 ms (p = 0.035), nocturnal HRVI increased from 6.1 to 8.0 ms (p = 0.026), and the SD of the average N-N interval increased from 37 to 41 ms (p = 0.020). None of these indexes changed significantly in the control group. Additionally, compared with the control group, the pro-atrial natriuretic peptide levels declined significantly in the NIMV group (p = 0.013). CONCLUSIONS: NIMV applied nocturnally over 3 months may improve HRV, reduce circulating natriuretic peptide levels, and enhance the functional performance of patients with advanced but stable COPD. While not definitive due to small sample size, these data suggest that nocturnal NIMV may reduce the impact of cardiac comorbidities in COPD patients.     

胃癌中ANP表达与BMP信号通路相互作用对细胞侵袭、转移的影响

目的探讨心房钠尿肽(atrial natriuretic peptide,ANP)在胃癌组织和细胞中的表达及ANP对胃癌细胞侵袭转移的作用。方法采用免疫组化EnVision法检测60例胃癌组织及正常胃黏膜组织中ANP的表达;培养胃癌细胞MGC-803,并将其分为两组:加入ANP组(ANP阳性组)、未加入ANP组(ANP阴性组)。采用Transwell实验检测两组胃癌细胞MGC-803的侵袭性,利用CCK8法检测两组胃癌细胞MGC-803的增殖能力。采用Western blot法检测两组胃癌细胞MGC-803中BMP信号通路相关蛋白表达量的变化及Ki-67、MMP-2和MMP-9蛋白表达量的变化。结果免疫组化检测ANP定位于胃黏膜细胞的胞质中,且在胃癌组织中的阳性率明显低于正常胃组织,差异有统计学意义(P<0.05);CCK8法、Transwell实验结果显示,ANP阳性组胃癌细胞的增殖速度及侵袭性比ANP阴性组低,差异有统计学意义(P均<0.05)。Western blot法检测ANP阳性组中BMP信号通路相关蛋白Smad1/5表达量比ANP阴性组低,差异有统计学意义(P<0.05);BMP6/7和p-Smad1/5的表达升高,差异有统计学意义(P均<0.05)。Western blot法检测ANP阳性组中Ki-67、MMP-2和MMP-9蛋白比ANP阴性组低,差异有统计学意义(P均<0.05)。结论胃癌组织中ANP的表达低于正常胃组织,ANP可能通过激活BMP信号通路抑制胃癌细胞MGC-803的增殖、侵袭和转移,为胃癌的发病机制及靶向治疗提供新思路。     

CGMP Levels Following ANF Challenge are Markers of Subsequent Successful Reversion of Lone Atrial Fibrillation to Sinus Rhythm

The aim of the present study was to assess whether cGMP release to ANP stimulation can be a biochemical marker of subsequent successful electrical cardioversion of lone atrial fibrillation to sinus rhythm. For this purpose, we studied 13 patients with chronic, lone atrial fibrillation of less than one year's duration who presented to our laboratory for electrical therapy of their arrhythmia. Prior to electrical cardioversion, peripheral venous cGMP levels were assessed at baseline and following an tntravenous challenge of 50 Ug human ANP. Venous blood samples for cGMP assessment were taken a) at baseline, b) 5 and 10 mins after the end of ANP infusion. ANOVA of repeated measures was used for statistical analysis. Eight of the study patients were successfully cardioverted to sinus rhythm, while the remaining 5 were not. Although no difference was noted between the two groups regarding the mean time of arrhythmia duration as well as left atrial and ventricular dimensions, ANP stimulation provoked significantly greater cGMP release in patients whose arrhythmia reverted to sinus rhythm, when compared with that of patients whose arrhythmia persisted (p<0.001). Therefore, cGMP levels following ANP challenge might discriminate between patients with chronic AF who are going to be successfully cardioverted and those who are not. These findings imply that the underlying atrial disease might be different in extent/nature between patients with lone AF responsive to cardioversion and those with resistant arrhythmia.     

The biochemical pharmacology of renin inhibitors: Implications for translational medicine in hypertension, diabetic nephropathy and heart failure: Expectations and reality

The renin-angiotensin-aldosterone system (RAAS) plays a dominant role in the pathophysiology of hypertension, Diabetes mellitus (DM), chronic kidney disease (CKD) and chronic heart failure (CHF). Therefore, drugs that block key components of the RAAS such as ACE inhibitors (ACEi) and angiotensin receptor blockers (ARBs) have gained wide clinical use for these indications. Despite progress, the morbidity and mortality of patients treated with ACEi or ARBs remain high. Small molecules that directly inhibit renin (DRI) and are orally active have also been developed and one such drug, aliskiren, was introduced into clinical use for treatment of hypertension in 2007. Further clinical trials aimed to expand the therapeutic use of aliskiren are in progress for CKD-DM and CHF. In this review we analyze and review the translational medicine prospects of aliskiren in respect to the biochemical pharmacology of the RAAS, the marketed RAAS modulators and the new emerging science regarding the role of prorenin, renin and renin receptors in cardiovascular biology and disease. The information already gained with aliskiren, raises questions regarding the advantages of DRIs as monotherapy compared to marketed ACEis and ARBs, their potential added value in combination with other RAAS modulators and other unproven benefits in relation to prorenin and renin receptor biology. This review will also indicate basic and clinical research needs that are critical to determine whether DRIs can provide meaningful added medical benefits over contemporary medicines that regulate the RAAS, and the need to identify patients that are more likely to benefit from DRIs and any possible long term adverse effects.