心绞痛患者血浆神经肽Y释放动态观察及相关因素影响的研究

采用放射免疫法测定心绞痛患者（３０例）血浆神经肽Ｙ（ＮＰＹ）含量变化。结果显示：心绞痛患者血浆ＮＰＹ含量为（１４５４±７９８）ｎｇ／Ｌ，明显高于正常组（７５１±３０４）ｎｇ／Ｌ，Ｐ＜００１，观察其中２０例不稳定型心绞痛患者治疗前后ＮＰＹ含量变化，发现无论于心绞痛发作即刻或心绞痛发作期（１日发作１～３次），血浆ＮＰＹ水平升高，经治疗后症状缓解，ＮＰＹ含量明显下降，前后比较，有统计学意义（Ｐ＜００５）。伴高血压、左室肥大患者血浆ＮＰＹ含量明显高于不伴有者（Ｐ＜００１），既往有吸烟史的心绞痛患者，ＮＰＹ水平明显高于无吸烟史者（Ｐ＜００５），冠脉造影前后血浆ＮＰＹ含量无明显变化     

戊酸雌二醇对18月龄雌性大鼠下丘脑内阿片肽基因表达的调节作用

目的观察戊酸雌二醇对１８月龄雌性老年前期大鼠下丘脑、垂体和血浆内阿片肽含量及下丘脑内阿片肽ｍＲＮＡ水平的影响。方法采用ＮｏｒｔｈｅｒｎＢｌｏｔ和神经肽放免测定法。结果与５月龄青年大鼠比较，１８月龄大鼠下丘脑和血浆β－内啡肽（β－ＥＰ）、亮氨酸脑啡肽（Ｌ－ＥＮＫ）、强啡肽Ａ１－１３（ＤｙｎＡ１－１３）含量明显降低（Ｐ＜０．０５或０．０１）；垂体β－ＥＰ、Ｌ－ＥＮＫ含量升高，ＤｙｎＡ１－１３含量降低（Ｐ＜０．０１）；下丘脑阿黑皮素原（ＰＯＭＣ）基因和脑啡肽原（ｐｒｏｅｎｋｅｐｈａｌｉｎ）基因ｍＲＮＡ水平明显低于青年大鼠（Ｐ＜０．０５）。肌注戊酸雌二醇后，老年前期大鼠下丘脑ＰＯＭＣ和ｐｒｏｅｎｋｅｐｈａｌｉｎ基因ｍＲＮＡ水平明显升高（Ｐ＜０．０５）；下丘脑β－ＥＰ含量增加（Ｐ＜０．０５）；垂体β－ＥＰ降低，Ｌ－ＥＮＫ升高；血浆ＤｙｎＡ１－１３含量增加（Ｐ＜０．０５）。结论戊酸雌二醇促进老年前期雌性大鼠下丘脑β－ＥＰ基因表达，增强其合成能力，而对Ｌ－ＥＮＫ和ＤｙｎＡ代谢的影响不明显。     

实验性肝硬化血浆内源性阿片肽含量的变化及其意义

目的：通过检测实验性肝硬化变各阶段三种内源性阿片肽（ＥＯＰ）血浆浓度变化，探讨其与肝硬化高动力循环状态及腹水形成的关系，方法：应用放射免疫法测定了四氯化碳（ＣＣｌ４）诱发大鼠肝硬化过程中血浆三种ＥＯＰ的含量变化。结果：结果显示肝硬化腹水组及肝硬化无腹水线血浆亮啡肽（Ｌ－ＥＮＫ）强啡肽（ＤｙｎＡｌ－１３）含量均显著高于正常对照组（Ｐ〈０．０１，Ｐ〈０．０５），而且升高的水平与肝功能损害的程度呈显著正     

肝硬化患者血浆内皮素浓度观察

用放射免疫分析法测定２２例肝硬化及１３例正常人血浆内皮素（Ｅｎｄｏｔｈｅｌｉｎ，ＥＴ）含量，２２例肝硬化患者血浆ＥＴ明显高于正常人（各为９８．４±１３．１ｐｇ／ｍｌ和４６．５±８．２ｐｇ／ｍｌ，Ｐ＜０．０１）；无腹水组血浆ＥＴ为１３９．０±２０．６ｐｇ／ｍｌ，高于腹水组（Ｐ＜０．０１）；腹水组无功能性肾衰时腹水组无功能性肾衰者血浆ＥＴ浓度，与伴有功能性肾衰组相比，两者无显著差别（Ｐ＞０．０５）。无显著差别（Ｐ＞０．０５）。提示血浆ＥＴ参与血管紧张度的维持，可能与肝硬化时腹水形成及功能性肾衰有一定关系。     

肝性脑病患者脑脊液生长抑素和甲硫氨酸脑啡肽含量变化及意义

为探讨脑肠肽（ＢＧＰ）在肝性脑病（ＨＥ）发生和发展中的作用，应用放射免疫法测定了１０例ＨＥ患者和１０例无肝性脑病对照者脑脊液（ＣＳＦ）生长抑素（Ｓｓ）、甲硫氨酸脑啡肽（ＭＥ）的含量。结果表明，ＨＥ患者ＣＳＦＭＥ含量明显减低（Ｐ＜０．０５），ＳＳ含量明显增加（Ｐ＜０．０５）。ＭＥ含量与ＨＥ程度呈显著负相关（Ｐ＜＜０．０５），与ＣＳＦ糖和蛋白含量关系不密切（Ｐ＞０．０５）。随ＨＥ患者存活时间延长，ＭＥ含量渐增加（ｐ＜０．０１）。提示ＢＧＰ可能参与ＨＥ的发生发展并能在ＣＳＦ中反应出来，ＨＥ患者的一些神经精神症状亦可能与中枢神经元释放ＢＧＰ异常有关。     

苯那普利对自发性高血压大鼠神经肽Y含量的影响

目的为探讨苯那普利对自发性高血压大鼠神经肽Ｙ（ＮＰＹ）含量的影响及其与高血压治疗的关系。方法本文选择了自发性高血压大鼠（ＳＨＲ）１６只,每８只为一组分成Ａ、Ｂ两组。Ａ组应用苯那普利进行治疗;Ｂ组作为对照组,用生理盐水治疗,４周后分别测定其血压,并测定其血浆以及重要器官组织中神经肽Ｙ的含量。结果Ａ组血压显著低于Ｂ组（Ｐ＜０．０１）。Ａ组血浆ＮＰＹ含量与Ｂ组比较显著降低（Ｐ＜０．０５）;ＮＰＹ在Ａ组的肝、肺及肾组织中的含量也明显低于Ｂ组（Ｐ分别＜０．０５,＜０．０５,＜０．０１）;而心、脑组织中ＮＰＹ略有降低,但无统计学意义（Ｐ＞０．０５）。结论苯那普利对自发性高血压大鼠体内ＮＰＹ含量变化的影响,可能与其治疗作用有关。     

血浆内源性阿片肘升高与肝硬化外周动脉扩张及腹水形成的关系

目的：探讨血浆三种内源笥阿片肽浓度变化，以了解它与肝硬化外周动脉扩张及腹水形成的关系。方法：用辨免法检测了２０例正常人，２０例非肝病及５０例肝硬化患者的血浆强啡肽（ＤｙｎＡ１－１３），亮啡肽（Ｌ－ＥＮＫ）和β－内啡肽（β－ＥＰ）。结果：肝硬化无腹水组和有腹水组血浆ＤｙｎＡ１－１３和Ｌ－ＥＮＫ浓度均明显高于正常对照组和非肝病对照组（Ｐ〈０．０１）；随病情加重，ＤｙｎＡ１－１３和Ｌ－ＥＮＫ均呈上升趋势     

高血压病患者血浆5种神经肽水平的临床研究

目的探讨高血压病患者血浆５种神经肽：〔神经肽Ｙ（ＮＰＹ）、降钙素基因相关肽（ＣＧＲＰ）、Ｐ物质（ＳＰ）、脑啡肽（ＥＮＫ）及神经降压肽（ＮＴ）〕的水平在高血压病发病中的临床意义。方法用放射免疫分析法测定３０例高血压病患者血浆５种神经肽的水平；并与３０例正常对照组比较。结果３０例高血压病组血浆ＮＰＹ、ＣＧＲＰ、ＳＰ、ＥＮＫ、ＮＴ水平与各自的正常对照组比较差异均非常显著（Ｐ＜０．００１）。结论５种神经肽均参与了高血压病的发病机理及病理生理过程；５种神经肽水平与高血压病严重程度密切相关     

动脉血酮体比对老年肝性脑病患者肝脏能量储备的研究

测定３１例老年肝性脑病、２８例非老年肝性脑病、１１例非肝病性脑病患者及１９例健康老年人的动脉血酮体比（ＡＫＢＲ），结果显示，在未发生肝性脑病时，老年肝病思者ＡＫＢＲ明显低于非老年肝病患者及健康老年人（０．７２±０．２３与０．９５±０．３６及１．５８±０．３１，Ｐ＜０．０５）；发生肝性脑病时，老年肝病患者ＡＫＢＲ也明显低于非老年肝病及非肝病性脑病患者（Ｐ＜０．０５），且ＡＫＢＲ与其预后有密切关系。提示ＡＫＢＲ能准确评价老年肝性脑病患者肝脏能量储备，并能预测其预后。     

戊酸雌二醇对18月龄雌性大鼠下丘脑内阿片肽基因表达的调节…

目的 观察戊酸雌二醇对１８月龄雌性老年前期大鼠下丘脑，垂体和血浆内阿片肽含量及下丘脑内阿片肽ｍＲＮＡ水平的影响。方法 采用ＮｏｒｔｈｅｒｎＢｌｏｔ和神经肽放免测定法，结果 与５月龄青年大鼠比较，１８月龄大鼠丘脑和血浆β－内啡肽（β－ＥＰ），亮氨酸脑啡肽（Ｌ－ＥＮＫ）强啡肽Ａ１－１３（ＤｙｎＡ１－１３）含量明显降低（Ｐ〈０．０５或０．０１），垂体β－ＥＰ，Ｌ－ＥＮＫ含量升高，ＤｙｎＡ－１３含量降低（     

肝硬化患者的内毒素和脂多糖结合蛋白水平及其与预后的关系

背景脂多糖结合蛋白(LBP)是介导脂多糖(LPS)活化单核/巨噬细胞的关键因子。尽管内毒素在慢性肝病和肝硬化中具有重要作用,但其结合蛋白在肝硬化中的意义尚不清楚。目的了解肝硬化患者的内毒素和LBP水平,并探讨其与预后的关系。方法分别以基质显色法鲎试验和酶联免疫吸附测定(ELISA)检测肝硬化患者的血浆内毒素和LBP水平;伴腹水患者同时测定腹水内毒素和LBP水平,并进行2个月的短期随访,记录存活情况。结果肝硬化患者的血浆内毒素和LBP水平均显著高于健康对照者(P<0.05),其中伴腹水患者的血浆内毒素水平显著高于无腹水患者(P<0.05)。Child鄄PughC级肝硬化伴腹水患者的腹水内毒素水平显著高于B级患者(P<0.05),而B级患者的血浆LBP水平显著高于C级患者(P<0.05)。短期随访显示肝硬化伴腹水死亡患者的腹水内毒素水平显著高于存活者(P<0.05)。结论肝硬化患者的血浆内毒素和LBP水平均升高,LBP水平升高可能是对肝硬化肠源性内毒素血症的一种持续的慢性炎症应答。腹水内毒素水平可以作为肝硬化伴腹水患者短期生存的一个预测指标。     

血浆置换治疗慢性重型肝炎影响疗效的因素分析

目的分析血浆置换治疗慢性重型肝炎影响疗效的因素。方法回顾性分析血浆置换治疗慢性重型肝炎86例的临床资料,对影响临床疗效的因素进行分析。结果49例患者痊愈或明显好转,存活率为56.98%;37例病情恶化或死亡,病死率43.02%。死亡组年龄大于存活组(P<0.01);在肝硬化基础上发生的重型肝炎患者血浆置换的疗效低于在慢性肝炎基础上发生的重型肝炎(P<0.01);存活组凝血酶原活动度(PTA)、血清总胆固醇、甲胎蛋白及白蛋白水平高于死亡组,而血清总胆红素、内毒素水平低于死亡组(P<0.01);血浆置换治疗慢性重型肝炎早、中期患者疗效高于晚期患者疗效(P<0.01),慢性重型肝炎存在的并发症也影响血浆置换的疗效。讨论血浆置换的疗效与患者的年龄、治疗前的血清总胆红素、凝血酶原活动度(PTA)、血清总胆固醇、甲胎蛋白、白蛋白及内毒素水平有关。血浆置换治疗后胆红素水平反跳明显、PTA恢复不明显或甚至更低者的疗效差。我们认为血浆置换治疗>5或6次后病情仍未改善,血清胆红素水平下降不明显或反跳幅度明显、PTA恢复不明显或甚至更低者,有条件者应尽早施行肝移植术。     

乙型肝炎肝硬化患者外周血单个核细胞Toll样受体2、4的表达

目的 探讨乙型肝炎(乙肝)肝硬化患者中Toll样受体(TLR)2、4表达与细胞因子的相关性.方法 采用随机数字表法随机收集35例乙肝肝硬化患者与35例健康对照者的静脉抗凝血.ELISA检测血TNF-α含量.分离两组外周血单个核细胞(PBMC),流式细胞仪检测PBMC表面TLR2、4表达.实时荧光定量PCR检测每份PBMC中TLR2、4 mRNA的表达水平.正态分布均数比较采用t检验和单因素方差分析,非正态分布数据采用Mann-Whitney U检验、Kruskal-Wallis H检验和Spearman相关分析.结果 肝硬化组的血TNF-α水平明显高于对照组(33.52 ng/L比6.07 ng/L,Z=6.584,P<0.01),且随着Child-Pugh评分的增加而升高.肝硬化组PBMC中TLR2阳性细胞率明显高于对照组(20.65%比12.04%,Z=-4.458,P<0.01),与血TNF-α水平存在正相关(r=0.448 3,P<0.05),且随着Child-Pugh评分的增加而升高.两组PBMC中TLR4阳性率差异无统计学意义.肝硬化组PBMC中TLR2/还原型磷酸甘油醛脱氢酶(GAPDH)mRNA表达水平明显高于对照组(0.234 2比0.043 1,Z=-6.83,P<0.01),与血TNF-α水平存在正相关(r=0.411 1,P<0.05),且随着Child-Pugh评分的增加而升高.两组PBMC中TLR4 mRNA表达水平差异无统计学意义.结论 肝硬化患者PBMC中TLR2表达水平明显增高,与血TNF-α水平及肝硬化的严重程度呈正比,但TLR4表达水平无明显变化,提示在乙肝肝硬化患者中,是TLR2而非TLR4在肝硬化的进展过程中具有重要作用.     

Atrial natriuretic peptide, plasma renin activity, plasma volume, systemic vascular resistance and cardiac output in patients with cirrhosis

The present study aimed to assess relationships between plasma levels of atrial natriuretic peptide (ANP) and plasma volume, systemic vascular resistances, cardiac output and plasma renin activity in patients with cirrhosis. Thirty patients were included: eight with no history of liver disease were used as controls; 22 patients had biopsy-proven alcoholic cirrhosis without ascites (n = 11) and with ascites (n = 11). Mean ANP plasma level was significantly higher in both groups of cirrhotic patients than in controls (P less than 0.05). In the control group, ANP and plasma renin activity were inversely correlated (P less than 0.05) but no correlation was found in cirrhotic patients. In the group of patients with ascites, ANP plasma levels were inversely correlated to plasma volume (P less than 0.05) and to cardiac output (P less than 0.01) and directly correlated to systemic vascular resistances (P less than 0.01). Using multiple regression analysis, ANP remained correlated only with systemic vascular resistances (P less than 0.05). These results suggest that cirrhotic patients have high plasma levels of ANP whether or not they have ascites. In the light of current knowledge of ANP actions, the relationships between ANP plasma levels and plasma volume, cardiac output, and systemic vascular resistances are paradoxical in cirrhotic patients with ascites. ANP does not seem to play a critical role in the pathogenesis of sodium and water retention observed in these patients.     

Abnormal sympathetic and renal response to sodium restriction in compensated cirrhosis

It has been proposed that in liver cirrhosis portal hypertension causes splanchnic vasodilation and this induces blood volume expansion to maintain blood pressure. The current study was designed to explore the homeostatic response to sodium restriction, a maneuver aiming to contract blood volume, in compensated cirrhosis. Mean blood pressure, sympathetic nervous activity, and proximal sodium reabsorption were evaluated in 16 healthy control and 21 nonazotemic cirrhotic patients (11 without ascites and 10 with ascites) under two experimental conditions: after 4 days on a free sodium diet (basal condition) and after 4 days on a restricted sodium diet (40 mmol/day). No differences were observed in basal conditions in the above parameters between control and cirrhotic patients without ascites. However, cirrhotic patients with ascites showed lower basal values of mean blood pressure and higher basal levels of both plasma norepinephrine and fractional proximal sodium reabsorption than controls. Neither control nor cirrhotic patients with ascites showed significant changes in the measured parameters after sodium restriction. In contrast, in nonascitic patients, this maneuver induced an elevation in plasma norepinephrine concentration (164.4 +/- 24.6 vs. 270.1 +/- 24.9 pg/mL; mean +/- SEM; P less than 0.005) and in fractional proximal sodium reabsorption (86.4 +/- 2.1 vs. 91.8% +/- 0.5%; P less than 0.01). In addition, the nonascitic cirrhotic patients became hypotensive compared with controls (80.9 +/- 1.6 vs. 88.5 +/- 4.8 mm Hg; P less than 0.05) when subjected to the low-sodium diet. In patients without ascites, under conditions of sodium restriction, the decrease in mean arterial pressure correlated inversely with the increase in plasma norepinephrine concentration (r = -0.713; P less than 0.05), whereas the levels of plasma norepinephrine correlated directly with fractional proximal sodium reabsorption (r = 0.893; P less than 0.01). These findings suggest that ineffective circulatory volume is detected in nonascitic cirrhotic patients only under conditions of sodium restriction, but it is always present in cirrhotic patients with ascites, irrespectively of the amount of sodium in the diet. These results are compatible with the existence of fixed arterial vasodilation in cirrhosis.     

Uncoupling of sympathetic nervous system and hypothalamic-pituitary-adrenal axis in cirrhosis

Background and Aim: The hypothalamic‐autonomic nervous system (HANS) axis and the hypothalamic‐pituitary‐adrenal (HPA) axis are stimulated in parallel in response to stress factors under healthy conditions. This physiological synergism of the axes aims at optimizing anti‐inflammatory actions. Therefore, we investigated whether this synergism is altered in patients with liver cirrhosis. Methods: As a typical marker of the HANS axis neuropeptide Y (NPY is a neurotransmitter of the sympathetic nerve terminal) and of the HPA axis, cortisol together with adrenocorticotropic hormone (ACTH) and cortisol‐binding globulin (CBG), were measured in samples from control subjects and patients with liver cirrhosis. Results: Plasma NPY was found to be increased in cirrhotic patients compared to control subjects (P < 0.01). This increase was observed to be independent of the severity of liver disease (Child class). Serum cortisol was decreased in cirrhotics, particularly in patients with Child A cirrhosis. Plasma NPY was positively correlated with serum cortisol in control subjects (r = 0.32, P < 0.05) reflecting the parallel activation of both axes under the normal condition. However, serum cortisol was not correlated with plasma NPY in cirrhotic patients. For the subgroup of Child A patients, even a negative correlation between NPY and cortisol was observed (r = ?0.43, P < 0.05). No significant change in serum levels of ACTH and its positive correlation with serum cortisol was observed in cirrhotic patients. Conclusions: The present study demonstrates that the two stress axes seem to act in parallel fashion in control subjects but are uncoupled in liver cirrhosis. We discuss how uncoupling of the two anti‐inflammatory axes can occur and may contribute to the increased susceptibility for infections and lethal complications in cirrhotic patients.     

病毒性肝炎患者血浆亮啡肽的变化及其意义

目的 探讨病毒性肝炎患者血浆亮啡肽(LENK)的变化规律及意义。方法 用放射免疫法(RIA)检测了67例各型肝炎病人及10例正常人LENK含量变化,并观察其与机体免疫学指标的关系。结果 LENK含量在各型肝炎显著高于正常对照(P<0.05),且慢重肝和慢性肝炎重度显著高于其它各型肝炎(P<0.05);在慢性肝炎中,LENK与血清总胆红素呈正相关,与白蛋白和凝血酶原活动度呈负相关。结论 病毒性肝炎时LENK显著升高,并与肝损害程度基本一致,它可能参与了病毒性肝炎的病理损害过程,并与某些临床症状有关,可作为评价肝功能的一项辅助指标。     

高血压病患者脑钠肽水平与心脏测量指标的相关性

目的探讨高血压病患者脑钠肽（brain natriuretic peptide,BNP）水平与心脏测量指标的相关性。方法选择57例明确诊断为高血压病的患者和30例年龄相仿的健康对照者。测定其室间隔厚度（left ventricular septum thickness,LVST）、左心室后壁厚度（posterior wall thickness,PWT）、左室质量指数（left ventricular mass index,LVMI）、左室舒张末内径（left ventricular end diastolic diameter,LVEDD）和BNP浓度,并进行对照比较。结果高血压病患者血浆中BNP浓度明显较健康对照组升高（P<0.01）,并随血压分级增加而升高;BNP与LVST、PWT、LVMI、LVEDD呈显著正相关（r=0.52,P<0.05;r=0.46,P<0.05;r=0.42,P<0.05;r=0.40,P<0.01）。伴左室肥厚的高血压病患者组的血浆BNP水平较不伴左室肥厚的高血压病患者组显著升高（P<0.05）。结论高血压病患者的血浆BNP浓度显著升高,BNP浓度与血压分级密切相关,并与左室肥厚相关。     

原发性高血压患者血浆神经肽Y的变化

目的通过观察血浆神经肽Y(NPY)在原发性高血压(EH)患者中浓度的变化,探讨血浆NPY在EH病理生理进程中的作用及在EH靶器管损害中的意义。方法选EH患者115例,以左室肥厚、脑卒中与肾功能损害为靶器官损害,其中伴有左室肥厚者21例,伴有脑卒中者13例、伴有肾功能损害者11例,为单一靶器官损害组,伴有两种或两种以上靶器官损害者19例为联合靶器官损害组,余下51例为单纯高血压而无靶器官损害组,体检健康者30例为对照组。取空腹静脉血用放射免疫方法测定NPY的血浆浓度。结果1)EH患者血浆NPY浓度高于对照组(P<0.01),不同血压级别之间血浆NPY浓度亦存在显著性差异(F=76.717,P<0.01),且随着血压级别的上升而升高。血浆NPY浓度与平均动脉压呈正相关(r=0.86,P<0.01)。2)单一靶器官损害组血浆NPY浓度高于单纯高血压而无靶器官损害组,差异有非常显著意义(P<0.01)。联合靶器官损害组血浆NPY浓度高于单纯高血压而无靶器官损害组,差异有非常显著意义,而与单一靶器官损害组相比差异无统计学意义(P>0.05)。结论血浆NPY可能与EH的病理生理进程以及EH靶器官损害的发生和发展有关,检测血浆NPY浓度可作为评价EH进程及靶器官损害程度的指标。     

Increased plasma levels of neuropeptide Y in hepatorenal syndrome

BACKGROUND/AIMS: To investigate the relationship between neuropeptide Y (NPY), a potent renal vasoconstrictor peptide released upon marked stimulations of sympathetic nervous system (SNS), and renal and circulatory function in cirrhosis. METHODS: Plasma levels of NPY (radioimmunoassay) and norepinephrine and renal function parameters were determined in 17 healthy controls, nine patients with cirrhosis without ascites, and 37 patients with cirrhosis and ascites, of whom 12 had hepatorenal syndrome (HRS). RESULTS: Patients with ascites showed circulating levels of NPY similar to those of patients without ascites and controls (73+/-4, +/-4 and 68+/-4 pmol/l, respectively; NS). However, patients with HRS had significantly increased levels of NPY with respect to the other groups (110+/-6 pmol/l; P<0.001). NPY levels correlated inversely with renal plasma flow and glomerular filtration rate and directly with norepinephrine. In patients with HRS (n=6) treatment with terlipressin and albumin was associated with a marked improvement in circulatory and renal function and marked suppression of NPY and norepinephrine levels. CONCLUSIONS: Patients with HRS have increased levels of NPY which are related to circulatory dysfunction and SNS activation and may contribute to renal vasoconstriction.