肾脏衰老所致形态及功能变化及其机制研究进展

预计到2030年,大于65岁的人口会增加1倍,老龄化正严重影响着人类社会.随着平均寿命的延长,衰老导致器官功能退化的研究已引起人们极大地重视.肾脏是受衰老影响最明显的器官之一,大量研究表明衰老与肾脏生理、形态及功能变化有关,最终导致肾脏储备功能下降及慢性肾损伤.本文主要阐述肾脏衰老导致肾小球形态和功能的变化及近年来肾脏衰老机制研究的新进展.     

肾脏衰老所致形态及功能变化及其机制研究进展

预计到2030年,大于65岁的人口会增加1倍,老龄化正严重影响着人类社会.随着平均寿命的延长,衰老导致器官功能退化的研究已引起人们极大地重视.肾脏是受衰老影响最明显的器官之一,大量研究表明衰老与肾脏生理、形态及功能变化有关,最终导致肾脏储备功能下降及慢性肾损伤.本文主要阐述肾脏衰老导致肾小球形态和功能的变化及近年来肾脏衰老机制研究的新进展.     

肾脏衰老所致形态及功能变化及其机制研究进展

预计到2030年,大于65岁的人口会增加1倍,老龄化正严重影响着人类社会.随着平均寿命的延长,衰老导致器官功能退化的研究已引起人们极大地重视.肾脏是受衰老影响最明显的器官之一,大量研究表明衰老与肾脏生理、形态及功能变化有关,最终导致肾脏储备功能下降及慢性肾损伤.本文主要阐述肾脏衰老导致肾小球形态和功能的变化及近年来肾脏衰老机制研究的新进展.     

重视中老年男性性腺功能减退的研究

一、概述 衰老是自然界一切生命必然要经历的过程,表现为各个器官形态结构和生理功能的退行性变化,睾酮水平下降是男性性腺功能减退最直接的表现,是衰老的特征之一.影响睾酮水平的原因既有中枢性亦有睾丸性.     

腹膜衰老机制的研究进展

机体在随着年龄增长的过程中,其全身各个器官、组织、细胞都发生着衰老的变化。腹膜衰老是机体衰老的一部分,在衰老过程中,同样出现各种形态、结构和功能上的变化。     

线粒体异常与卵巢储备功能减退的研究进展

卵巢储备功能减退为妇科常见内分泌疾病,是女性卵巢功能逐渐下降的早期阶段。近年来研究表明,线粒体功能异常在人体及各种器官衰老的进程中产生重要影响。随着对线粒体研究的不断深入,越来越多研究显示卵巢组织中线粒体异常与卵巢储备功能减退密切相关。本文主要围绕卵巢储备功能减退过程中卵母细胞线粒体异常及其发生机制,以及通过调控线粒体延缓卵巢衰老等展开综述。     

细胞自噬与衰老的相关性研究进展

衰老是每个生命体从生到亡的必经阶段,自噬是继凋亡之后目前生命科学研究最热的领域之一。本文从细胞自噬功能增强和减弱两个角度,分析了其对衰老过程的影响,文中对关于衰老与自噬这两者之间相关性的研究进行了回顾,从分子水平分析了mTOR和AMPK信号通路及p53蛋白在衰老–自噬这一细胞适应内外环境重要的调节机制中的作用,从而提示细胞自噬可以调节细胞衰老进程,因此,利用细胞自噬来治疗某些衰老性疾病(癌症、心脑血管病、神经退行性疾病等)必将成为未来医学研究的重点。     

男性更年期综合征的研究现状

衰老是自然界一切生命现象的共同特征，表现为形态结构和生理功能的退行性变化。男性更年期是人体由成熟走向衰老的过渡阶段，多数男子是在不知不觉中度过的，没有任何临床症状，部分中老年男子则出现与女性更年期综合征相似的临床症状和体征，可以对多系统器官的功能造成不良影响，并降低生活质量，     

急性胆道感染所致多脏器损害发病机理的研究进展

目的 总结急性梗阻性胆管炎所致多器官损害发病机理的实验研究进展。方法 分析近10年来国内外有关急性梗阻性胆管炎所致多器官发病机理的文献报道。结果 已建立多种稳定、可靠的急性胆道感染动物模型、急性梗阻性管炎期间，枯否细胞（KCs)和吞噬与清除功能降低、肝细胞线粒体功能损害、KCs对肝细胞蛋白质合成功能的影响、肝脏损害对肺脏等远隔器官功能的影响及内毒素介导KCs激活并释放大量细胞因子是造成多器官损害的主要机理，结论 急性胆道感染造成多器官功能损害的病理生理机理十分复杂，其中KCs功能变化是造成多器官的重要原因。     

皮肤衰老机理及延缓衰老化妆品的研究进展

衰老（Aging）又称老化，是任何生物生命活动进程中的必经阶段，是生物体发育成熟后，随年龄增长而发生的渐进的、受遗传因素影响的、全身复杂的形态结构与生理功能不可逆的衰退过程。皮肤是人体最大的器官，担负着保护、感觉、调节体温、分泌、排泄和免疫等诸多方面的作用，随着年龄的增长，皮肤也会像人体的其他器官一样逐渐老化，功能减弱、丧失，产生各种病变等。本文就皮肤衰老机理及延缓衰老化妆品的研究进展综述如下。     

The causes and value of hyperphosphatemia in experimental strangulation obstruction

In model experiments with mongrel dogs, intestinal strangulation obstruction was induced by occluding the superior mesenteric veins, and a rise in the inorganic phosphate value of the blood was observed. The high inorganic phosphate values of the fluid exuding from the strangulated bowel suggest that intestinal factors associated with the strangulated bowel may be partly responsible for this elevated phosphatemia. However, hyperphosphatemia was also found in a model experiment in which the route through which the fluid was absorbed into the blood from the peritoneal cavity was interrupted by keeping the strangulated bowel in an intestinal bag. After this, in the model experiments in which a systemic blood pressure depression curve with a percentage reduction similar to that of the decreasing arterial blood pressure resulting from strangulation was produced (by exsanguination, and even by exsanguination with adequate perfusion of the gut), plasma inorganic phosphate values also increased. Therefore it is undeniable that systemic factors other than the above-mentioned local factors are related to the rise in plasma inorganic phosphate values in experimental strangulation obstruction. Because it is not possible to assert that phosphatemia is specific to intestinal strangulation, the importance of a rise in inorganic phosphate values in the early diagnosis of intestinal strangulation cannot be considered very great.     

Hyperplasia and neoplasia of the intestinal tract.

Measurements of RNA and DNA in the rat have been used to identify mucosal hyperplasia in the remaining gut within 48 h of partial intestinal loss. Structural adaptation of the ileum is still present 3 months after jejunal resection, whereas transection of the bowel produces merely transient hyperplasia. A humoral factor can be transmitted between rats linked in vascular parabiosis that is capable of stimulating intestinal cell proliferation. Humoral agents may also explain reduced adaptation of the distal bowel after jejunal bypass as opposed to equivalent resection. Although bile can initiate prompt ileal hyperplasia, the additional presence of pancreatic juice is needed to prolong this effect. Adaptation is controlled by luminal and systemic factors that are closely interlinked. Experimental intestinal carcinogenesis is promoted by proximal enterectomy.     

IL-10, IL-6, and TNF-alpha: central factors in the altered cytokine network of uremia--the good, the bad, and the ugly

It has been increasingly apparent that wasting and cardiovascular disease (CVD) is associated with a persistent systemic inflammatory response in end-stage renal disease (ESRD) patients. The reasons for the increased risk of inflammation in ESRD patients appear to be complex, including non-dialysis as well as dialysis-related factors. The combination of an impaired immune response coupled with persistent immune stimulation may have a role in the low-grade systemic inflammation and altered cytokine balance that characterizes the uremic state and which may translate into increased risk for vascular disease. The accelerated atherosclerotic process of ESRD may involve several interrelated processes, such as oxidative stress, endothelial dysfunction, and vascular calcification, in a milieu of constant low-grade inflammation with impaired function of neutrophils and T cells, as well as a dysregulated cytokine network. Although a large number of pro- and anti-inflammatory cytokines are of importance, available data suggest that the anti-inflammatory cytokine interleukin (IL)-10 and the mainly proinflammatory cytokines IL-6 and tumor necrosis factor-alpha (TNF-alpha) may play important roles in the development of Th imbalance, CVD and wasting in the uremic milieu. Given the strong association between proinflammatory cytokines and complications common in ESRD, such as vascular calcification and wasting, the potential role of both general and targeted anticytokine treatment strategies in ESRD patients needs further evaluation.     

The renal phosphate transport defect in normal mice parabiosed to X-linked hypophosphatemic mice persists after parathyroidectomy

The X-linked hypophosphatemic (Hyp) mouse is a model for human X-linked hypophosphatemia. Surgical joining of normal to Hyp mice by parabiosis results in the normal mice developing low renal retention of phosphate and hypophosphatemia. These results suggest a humoral component to the renal defect. To test whether this component could be parathyroid hormone, surgical parathyroidectomy (PTX) or sham surgery was performed in mice 3 weeks after parabiotic union (n greater than 20 per group). After an overnight fast, PTX mice were hypocalcemic and hyperphosphatemic relative to sham-operated control mice. PTX normal mice joined to PTX Hyp mice were significantly lower in plasma phosphate and higher in fractional excretion of phosphate [U/P phosphate/(U/P creatinine)] when compared with PTX normal mice joined to other PTX normals. To test for more specific evidence of altered renal transport function, renal brush-border membrane vesicles (BBMV) were prepared from these mice, and phosphate and glucose uptakes were measured. The phosphate/glucose transport ratio was lower in BBMV from Hyp mice, joined to either normal mice or to Hyp mice, when compared with that from normal-normal pairs. Moreover, BBMV from normal mice joined to Hyp mice had a significantly lower phosphate/glucose uptake ratio than BBMV from normal mice joined to other normal mice, and their activity approached that of BBMV derived from Hyp mice. Glucose uptake in BBMV was unaffected by parabiosis or genotype. In summary, parabiosis of normal mice to Hyp mice resulted in the development of phosphaturia and decreased BBMV phosphate transport in the normal mice. The persistence of the phosphate transport defect in parathyroidectomized mice suggests that parathyroid hormone is not the humoral factor contributing to these results.     

The effects of hemoglobin glutamer-200 (bovine) on the microcirculation in a canine hypovolemia model: a noninvasive computer-assisted intravital microscopy study

We sought to correlate in vivo microvascular, systemic function, hemodynamic, and oxygenation changes in autologous shed blood (n = 4) and hemoglobin glutamer-200 (Hb-200) (n = 4) resuscitations in hypovolemic dogs. Hemorrhage (approximately 40% blood loss) reduced mean arterial pressure to approximately 50 mm Hg and caused significant (P < 0.01) decreases in hematocrit, total hemoglobin, mean pulmonary arterial pressure, cardiac output, and oxygen delivery and significant (P < 0.01) increases in heart rate, systemic vascular resistance, and lactic acidosis. Significant (P < 0.01) changes in conjunctival microvascular variables also occurred, including a 19% decrease in venular diameter and 79% increase in average blood flow velocity. Shed blood resuscitation returned microvascular, systemic function, hemodynamic, and oxygenation variables to prehemorrhagic baseline values. In contrast, Hb-200 failed to restore hematocrit, total hemoglobin, cardiac output, oxygen delivery index, and systemic venous resistance to baseline, but it restored other systemic functions and all hemodynamic and microvascular changes. In addition, Hb-200 resuscitation in hypovolemic dogs (approximately 40% blood loss) did not cause extreme hemodilution or fatal outcome. This study confirms that real-time (in vivo) microvascular studies, which were conducted only in small rodent models in the past, can be performed simultaneously with systemic function, hemodynamic, and oxygenation studies in a large animal model for relevant data correlation. IMPLICATIONS: This is the first time that changes in the blood circulation have been studied, quantified, and correlated with systemic function, hemodynamic, and oxygenation changes in shock and during shock treatment in a large animal model. This study was performed by a new technology developed in-house to noninvasively and quantitatively study blood vessels in real time.     

Endocrine Pancreas: Summary of Observations Generated by Surgical Fellows

The present article summarizes scientific observations of the endocrine pancreas anatomy and physiology into a unifying hypothesis. The data were generated over the years by surgical fellows using human and rat isolated perfused pancreas models and in vivo islet microcirculation models. The endocrine pancreas secretes a hormonal milieu regulated by neural, hormonal, and nutritional stimuli and the microcirculation. Variation of the nutrient and hormone concentrations in the islet capillaries generates two levels of response. A first level of response is in the central nervous system (CNS). Cholinergic signals from the CNS regulate the islet microcirculation through internal and external gates. This regulation is mediated by nitric oxide (NO). The gates are endothelial cells found in feeding arterioles and capillaries of the islet capable of directing blood flow through changes in cellular shape. External gates shunt flow to the entire endocrine pancreas, and internal gates divert blood flow within the islet to expose selectively the appropriate cell type required for changes in hormonal milieu. The second level is within the islet. The islet cells respond directly to variations in hormonal and nutrient concentrations. There is extensive communication between the various types of islet cells regulated by NO and hormonal feedback loops. The two levels of response allow an appropriate hormonal milieu, which secreted into the bloodstream contributes to the maintenance of glucose homeostasis.     

Intraaortic Balloon Counterpulsation Improves Right Ventricular Failure Resulting From Pressure Overload

Background. Right ventricular (RV) dysfunction is common after heart transplantation, and myocardial ischemia is considered to be a significant contributor. We studied whether intraaortic balloon counterpulsation would improve cardiac function using a model of acute RV pressure overload.

Methods. In 10 anesthetized sheep, RV failure was induced using a pulmonary artery constrictor. Baseline measurements included mean systemic blood pressure, RV peak systolic pressure, cardiac index, and RV ejection fraction. Myocardial and organ perfusion were measured using radioactive microspheres.

Results. After pulmonary artery constriction, there was an increase in RV peak systolic pressure (32 ± 2 to 60 ± 3 mm Hg; p < 0.01) and a decrease in mean systemic blood pressure (68 ± 4 to 49 ± 2 mm Hg; p < 0.01), RV ejection fraction (0.51 ± 0.04 to 0.16 ± 0.02; p < 0.01), and cardiac index (2.48 ± 0.04 to 1.02 ± 0.11; p < 0.01). Blood flow to the RV did not change significantly, but there was a significant reduction in blood flow to the left ventricle. The initiation of intraaortic balloon counterpulsation (1:1) using a 40-mL intraaortic balloon inserted through the left femoral artery resulted in an increase in mean systemic blood pressure (49 ± 2 to 61 ± 3 mm Hg; p < 0.01), cardiac index (1.02 ± 0.11 to 1.45 ± 0.14; p < 0.05), RV ejection fraction (0.16 ± 0.02 to 0.23 ± 0.02; p < 0.01), and blood flow to the left ventricle.

Conclusions. In a model of right heart failure, the institution of intraaortic balloon counterpulsation caused a significant improvement in cardiac function. Although RV ischemia was not demonstrated, the augmentation of left coronary artery blood flow by intraaortic balloon counterpulsation and subsequent improvement in left ventricular function suggest that left ventricular ischemia contributes to RV dysfunction, presumably through a ventricular interdependence mechanism. Therefore, study of the safety and efficacy of intraaortic balloon counterpulsation in the management of patients with acute right heart dysfunction is warranted.     

Regional renal blood flow in normal and disease states

Renal function is intimately dependent on renal blood flow. Alterations in either total or regional renal blood flow have major consequences for renal function. Through homeostatic mechanisms the kidneys are able to maintain relatively stable rates of flow over a wide range of perfusion pressures. A combination of neural, endocrine, exocrine and autocrine signals serve to regulate renal blood flow at both local and systemic levels. Alterations in the balance of these systems occur in the presence of certain pathophysiological conditions and an understanding of the subsequent changes in regional renal blood flow distribution aids in the understanding of the associated changes in renal function. The regulation and distribution of regional blood flow and the effects of surgical and pathophysiological conditions on these factors are reviewed.     

Assessment of pulmonary/systemic blood flow ratio after first-stage palliation for hypoplastic left heart syndrome: development of a new index with the use of doppler echocardiography

OBJECTIVE: Circulatory maldistribution is believed to be a major cause of early death after first-stage palliation for hypoplastic left heart syndrome. Flow reversal in the reconstructed aorta may reflect the pulmonary/systemic blood flow ratio. The purpose of our study was to investigate the utility of arterial PO (2), arterial oxygen saturation, and a newly developed Doppler-derived flow index in predicting the pulmonary/systemic flow ratio after first-stage palliation for hypoplastic left heart syndrome. METHODS: Twenty-four infants who underwent first-stage palliation for hypoplastic left heart syndrome or a variant were studied. Superior vena cava blood samples were drawn to estimate the mixed venous saturation and permit calculation of the pulmonary/systemic blood flow ratio. Fifty-four samples were evaluated within the first 24 hours after surgery. Simultaneous blood draw and Doppler echocardiography were performed with interrogation in the distal aspect of the arch reconstruction. The ratio of the Doppler velocity-time integral of retrograde flow to the velocity-time integral of forward flow was calculated and compared with the pulmonary/systemic blood flow ratio RESULTS: The median mixed venous saturation for the 54 samples was low (38.5%; range, 18%-64%). The median calculated pulmonary/systemic blood flow ratio was 1.4:1 (range, 0.3:1 to 4. 2:1). Pulse pressure, mixed venous saturation, and arterial PO (2) were not statistically significant predictors of the measured pulmonary/systemic blood flow ratio. Although both aortic oxygen saturation (R (2) = 0.84, P <.01) and Doppler flow reversal ratio (R (2) = 0.94, P <.001) were significantly associated with the measured pulmonary/systemic blood flow ratio, the model coefficient of determination was greatest for Doppler flow reversal ratio. CONCLUSION: Measures of arterial oxygen saturation and arterial PO (2) may be misleading in assessing the circulatory status of infants after first-stage palliation for hypoplastic left heart syndrome. Doppler echocardiography, through use of the Doppler flow reversal ratio, provides a more useful measure of pulmonary/systemic blood flow ratio. Low mixed venous saturation after surgery may be due to factors other than pulmonary overcirculation, such as ventricular dysfunction and low cardiac output.