休克时糖皮质激素受体的变化及大剂量糖皮质激素抗休克治疗的受体机制

休克时糖皮质激素受体的变化及大剂量糖皮质激素抗休克治疗的受体机制△徐仁宝（第二军医大学病理生理教研室，上海２００４３３）ＡｂｓｔｒａｃｔＷｉｔｈｒａｄｉｏｌｉｇａｎｄｂｉｎｄｉｎｇａｓａｙａｎｄＳｃａｔｃｈａｒｄａｎａｌｙｓｉｓｉｔｈａｓｂｅｅｎｄｅ...     

癫痫大鼠海马和大服皮质糖皮质激素受体变化的观察

为了探讨糖皮质激素受体（ＧＲ）与癫痫发病机制间的关系，本研究免疫细胞化学ＰＡＰ法显示马桑内酯致痫大鼠海马和大脑皮质内ＧＲ的变化，并用显微图像分析仪进行检测分析，结果显示：ＧＲ主要表达在海马回的锥体细胞层、龋状回颗粒细胞及层大脑皮质各层、特别是Ⅳ、Ⅴ层。ＧＲ免疫反庆主要定位于细胞核内，胞浆内有较弱的免疫反应，图像分析及统计学处理表明，癫痫大鼠海在、齿状回、大脑皮持含ＧＲ免疫反庆阳性细胞数目，平均总面     

烫伤后大鼠肝胞液糖皮质激素受体变化的研究

本文用单克隆抗体检测法和放射配体结合测定法研究了烫伤大鼠肝胞液免疫活性糖皮质激素受体(GR_(IR))和糖皮质激素受体结合容量(GR_B)的变化。结果显示,烫伤后GR_(IR)和GR_B均明显减少,且两者下降的趋势基本平行,但GR_B下降的幅度比GR_(IR)约高10%。这说明应激后GR_B的减少主要是GR蛋白分子减少所致,但约有10%则归因于结合活性的变化。作者对这些变化的可能机制进行了讨论。     

大剂量糖皮质激素减轻大鼠创伤性脑水肿的受体机制

以创作性脑水肿的大鼠模型对作者提出的药理剂量的糖皮质激素通过低亲和力糖皮质激素受体的介导发挥治疗作用的假说作了验证。结果发现，只有当血浆地塞米松浓度达到１０＾－６ｍｏｌ／Ｌ时才能使脑水肿减轻，这减轻作用可被糖皮质激素受体的竞争性拮抗剂ＲＵ４８６所逆转，符合于我们的假说。     

失血后糖皮质激素受体,白细胞介素1的变化及二者的关系

本文观察不同失血后ＧＲ及ＩＬ－１的变化，并探讨二者的关系。大鼠分别接受假处理、１０％、２０％、３０％及４０％失血，不同处理后３ｈ肝、脑胞液ＧＲ随失血量增加而减少，血浆Ｌ－１性则相反，随失血量增加而增高；大鼠３０％失血后１－３ｈ，肝、脑胞液ＧＲ随休克时间延长而呈进行性减少，血浆ＩＬ－１活性变化之间，均呈显著的负相关。实验结果提示：失血后糖皮质激素受体减数调节，可能是血浆ＩＬ－１活性升高的重要原因。     

多发性骨髓瘤糖皮质激素受体研究进展

糖皮质激素是多发性骨髓瘤联合化疗的主要药物，通过与糖皮质激素受体持异结合抑制骨髓瘤细胞增殖，对糖皮质激素耐药的骨髓瘤细胞不仅糖皮质激素受体数量减少，而且功能异常。     

大鼠体外循环后血浆二胺氧化酶活性变化与肠屏障损伤的关系

目的：观察探讨体外循环（CPB）过程中大鼠血浆二胺氧化酶（DAO）活性变化规律及其与肠损伤指标变化的关系。 方法： 建立大鼠体外循环模型，按时点采血测定血浆DAO活性和D-乳酸、脂多糖(LPS)的浓度并进行统计分析。 结果： CPB后血浆DAO活性呈现双峰升高，第1峰值在CPB转流结束后即刻，时相上早于血浆LPS和D-乳酸的升高；第2峰值在CPB结束后3 h，在肠损伤指标变化峰值之后。 结论： CPB过程中肠粘膜屏障受到缺血和再灌注二次损伤的打击，血浆DAO活性作为反映肠损伤的指标特异性强，灵敏度高，对CPB术后病情判断和并发症防治提供参考。     

原发性癫痫患者糖皮质激素和糖皮质激素受体改变的研究

用放射配体结合分析，测定了４１例（男１６例，女２５例）原发性癫痫患者外周血白细胞糖皮质激素受体（ｇｌｕｃｏｃｏｒｔｉｃｏｉｄ ｒｅｃｅｐｔｏｒ ＧＲ），同时用放射免疫分析测定了患者血浆皮质醇（Ｆ），即糖皮质激素（ｇｌｕｃｏｃｒｔｉｃｏｉｄＧＣ），并与正常对照组比较。结果表明，无论年龄、性别及服用何种抗痫药物，原发性癫痫患者的ＧＣ都明显高于对照组（Ｐ〈０．０１）；ＧＲ都明显低于对照组，（Ｐ〈０．０     

Changes in platelet aggregation during cardiopulmonary bypass: comparison of poly-2-methoxyethylacrylate and heparin as a circuit coating material

At present, there are various biomaterials that have high biocompatibility. In particular, there are many types of coated circuits in cardiopulmonary bypass (CPB) systems. However, only a few clinical studies have investigated platelet aggregation caused by these coated circuits. In this study, a CPB system coated with poly-2-methoxyethylacrylate (X coating) was used to ascertain whether platelet aggregation could be suppressed during CPB, and a comparison was made between X coating and ordinary (covalently bonded) heparin coating. The subjects were 19 adult patients who were scheduled to undergo valve replacement or valvuloplasty. They were divided into two groups: group X (X coating) and group H (heparin coating). The platelet aggregation threshold index (PATI, grading curve) and β-thromboglobulin and plalelet factor IV levels were assessed preoperatively (control), 5 min after heparin administration, 10 and 60 min after the start of CPB, and 0 and 2 h after the end of CPB. The results indicated that platelet aggregation was reduced during CPB and that platelets were activated. The changes in platelet aggregation associated with the X coating were shown to be similar to those associated with heparin coating.     

浅低温体外循环围术期血清炎症介质的变化

目的 探讨浅低温体外循环围术期炎症介质的释放规律。方法 按入选标准筛选先天性心脏病患者24例，均采用浅低温体外循环心脏直视术，用酶联免疫吸附法测定患者术前（T1）、CPB30min（T2）、CPB结束后2h（T3）、12h（T4）、24h（T5）各时间点血清IL-6、IL-8、IL-10的浓度。结果 所有患者血清IL-6、IL-8、IL-10浓度在CPB开始后均升高（P〈0，01），于术后2h（T3）逐渐达高峰，术后12h（T4）逐渐下降，术后24h（T5）虽仍高于术前（T1）水平，但较高峰时（T3）已明显下降。结论 浅低温CPB术后患者血清IL-6、IL-8、IL-10浓度逐渐升高．术后2h达高峰．并于24h内恢复接近正常水平。     

Risk factors for disordered cerebral autoregulation during hypothermic cardiopulmonary bypass

Disordered cerebral autoregulation during cardiopulmonary bypass (CPB) is regarded as one of the causes of neurological dysfunction after cardiac surgery. However, little documentation of risk factors associated with cerebral autoregulation during CPB has been reported. Sixty consecutive patients undergoing coronary artery bypass were classified into subgroups according to whether they had preoperative cerebrovascular disease (CVD), hypertension (HT), or diabetes (DM). Cerebral oxygenation was monitored by jugular venous bulb oxygen saturation (SjvO₂) and near-infrared spectroscopy parameter (%Oxy-Hb) during the operation, and the relationships between these values and intraoperative parameters were evaluated. The results showed that SjvO₂ and %Oxy-Hb in the CVD+group were lower than in the CVD-group. Multiple stepwise regression analysis on SjvO₂ and %Oxy-Hb in the CVD+ group revealed that only MAP was a predictive factor and that there was a positive correlation between MAP and both SjvO₂ and %Oxy-Hb (r=.651,r=.693, respectively,P<0.0001). The coexistence of HT and DM increased the strength of the correlation between MAP and SjvO₂ (r=.863,p<0.0001) PaCO₂ was the predictive factor in the CVD- group. A positive correlation was found with SjvO₂ (r=.458,P>0.0001), and the correlation was stronger in patients without any risk factors (r=.671,P=0.0001). The results suggested that patients with CVD, HT, and DM may experience failure of cerebral pressureflow autoregulation and cerebrovascular reactivity during CPB.This paper was presented at the 52th Annual Meeting of the Japanese Association for Thoracic Surgery on October 7, 1999     

Usefulness of low-priming-volume cardiopulmonary bypass circuits and dilutional ultrafiltration in neonatal open-heart surgery

In neonate open-heart surgery, cardiopulmonary bypass (CPB) with extreme hemodilution induces an increased capillary permeability and accumulation of extravascular fluid, resulting in organ dysfunction. We evaluated the effects of a reduced priming volume for CPB and dilutional ultrafiltration (DUF) during neonatal open-heart surgery. Nineteen consecutive neonates with complete transposition of the great arteries who underwent an arterial switch operation were retrospectively assigned into two groups: the high-priming-volume circuit group (group A, n = 9) and the low-priming-volume circuit group (group B, n = 10). Patients in group B underwent surgery with a miniaturized CPB circuit and using the DUF technique. The priming volume of group B was nearly two-thirds that of group A. The water balance value after CPB and surgery was significantly lower in group B (–126 ± 118ml, –116 ± 116ml) than in group A (88 ± 218ml, 83 ± 165ml). Systolic blood pressure just after CPB was higher in group B (67.9 ± 9.1mmHg) than in group A (55.4 ± 10.3mmHg). Postoperative ventilatory support was shorter in group B (45 ± 19h) than in group A (68 ± 27h). In neonatal cardiac surgery, low-priming-volume CPB circuits and DUF improve the water balance during surgery and may attenuate any inflammatory reaction, which would help preserve postoperative organ function.     

Nonocclusive mesenteric ischemia after cardiopulmonary bypass

Nonocclusive mesenteric ischemia (NOMI) is a rare abdominal pathology caused by mucosal hypoperfusion without actual obstruction to the mesenteric arteries. We present a case of NOMI after a cardiopulmonary bypass operation. The patient was a 79-year-old woman with a history of hypertension and diabetes mellitus. A coronary bypass operation was performed with stable hemodynamic conditions, and continuous venovenous hemodialysis was performed on the second postoperative day because of renal insufficiency. After 24h of hemodialysis, the hematocrit level increased from 29.1% to 36.1%. The patient had some vague abdominal pain on the third postoperative day with abnormal laboratory values: leukocytes 17.10 × 10³/µl, creatine kinase 1085U/l, glutamic-oxyloacetic transaminase 6188U/l, and lactate dehydrogenase 8695U/l. Selective angiography showed diffuse stenosis of the superior mesenteric artery (SMA) without any occlusive findings on the major branches; the patient was therefore diagnosed with NOMI. An infusion of urokinase and prostaglandin E1 was started; however, disseminated intravascular coagulopathy had developed and the patient died on the 21st postoperative day as a result of multiple organ failure. The autopsy demonstrated extensive necrosis and hemorrhage in the small intestine without any occlusive findings on the major branches of the SMA.     

大鼠体外循环模型技术与实践

体外循环（CPB）技术经过50多年的不断发展，现已成为心脏外科常用的、安全有效的治疗手段，但由于非生理性的界面接触及血流改变，仍有许多与之相关的并发症困扰着临床。采用动物模型探讨CPB围手术期病理生理改变机制及各脏器功能保护策略是目前心脏外科面临的重要课题。大鼠模型具有费用低廉、装置简便、检测潜力大等优点，但由于动物体积较小，在装置设计和手术技术上有一定难度，所以在实际中尚未得到广泛应用。本文对大鼠CPB模型的技术要点进行总结分析，提出理想的、接近于临床的CPB小动物模型要求。     

Bronchoconstriction during alveolar hypocapnia and systemic hypercapnia in dogs with a cardiopulmonary bypass

The roles of the alveolar and systemic CO₂ on the lung mechanics were investigated in dogs subjected to cardiopulmonary bypass. Low-frequency pulmonary impedance data (Z_L) were collected in open-chest dogs with an alveolar CO₂ level (FA_CO2)$(\text{F}{\text{A}}_{\text{C}{\text{O}}_2})$ of 0.2–7% and during systemic hypercapnia before and after elimination of the vagal tone. Airway resistance (R_aw), inertance (I_aw), parenchymal damping (G) and elastance (H) were estimated from the Z_L. The highest R_aw observed at 0.2% FA_CO2$\text{F}{\text{A}}_{\text{C}{\text{O}}_2}$, which decreased markedly up to a FA_CO2$\text{F}{\text{A}}_{\text{C}{\text{O}}_2}$ of 2% (212 ± 24%), and remained unchanged under normo- and hypercapnia (FA_CO2$\text{F}{\text{A}}_{\text{C}{\text{O}}_2}$ 2–7%). These changes were associated with smaller decreases in I_aw (−16.6 ± 3.7%), mild elevations in G (25.7 ± 4.7%), and no change in H. Significant increases in all mechanical parameters were observed following systemic hypercapnia; atropine counteracted the R_aw rises. We conclude that severe alveolar hypocapnia may contribute to minimization of the ventilation–perfusion mismatch by constricting the airways in poorly perfused lung regions. The constrictor potential of systemic hypercapnia is mediated by vagal reflexes.     

Role of nitric oxide in regulation of systemic vascular resistance during and after cardiopulmonary bypass

Cardiopulmonary bypass (CPB) is known to result in the abnormal production of vasoactive substances contributing to the changes in hemodynamics such as systemic vascular resistance (SVR) during and after CPB. Nitric oxide (NO) is an inflammation-mediated vasoactive substance that plays a role in the whole-body inflammatory response induced by CPB. We evaluated the role of NO in the regulation of SVR during and after CPB. Fifteen patients underwent open-heart surgery for valvular heart disease. The perfusate blood temperature of CPB was set to 34°C. The plasma levels of NO metabolites (NO ₂ ⁻ +NO ₃ ⁻ ), prostaglandin E₂ (PGE₂), bradykinin (BK), and systemic vascular resistance index (SVRI) were measured before CPB and 0, 12, and 24 h after CPB. The plasma level of NO metabolites increased gradually after CPB (pre-CPB, 26.3 ±4.4; 0h, 33.7±6.5; 12 h, 49.8±11.1; 24 h, 43.1±7.5 μM). SVRI decreased gradually after CPB (pre-CPB, 2361±364; 0h, 2048±216; 12 h, 1590±308; 24 h, 1727±435 dyne·s·cm⁻⁵·m²). There was a significant inverse correlation between SVRI and the plasma level of NO metabolites as a whole (r=−0.674,P<0.0001). No significant correlations were observed between SVRI and the other vasoactive substances PGE₂ and BK. These findings demonstrated that NO production increased gradually during and after CPB in association with the decrease in SVR. Part of this study was presented at the 2nd annual meeting of the Japan Society for Adaptation Medicine on February 27, 1998     

腺苷注射液对体外循环术中心肌保护作用的研究

目的:通过观察体外循环(CPB)中使用腺苷心肌停博液对CPB围术期心肌酶学及相应促炎性细胞因子释放的影响,探讨它减轻CPB术中心肌损害的作用。方法:选择47例主动脉阻断时间在30分钟以上的心脏直视手术患者,随机分为实验组23例,对照组24例。实验组在常规CPB术中,心脏灌注液中加入腺苷2mmolL,对照组不用腺苷注射液。分别在手术开始前、主动脉阻断后30分钟,主动脉开放后30分钟、12小时、24小时抽取桡动脉血,检测CKMB、采用ELISA法测定血浆细胞因子(TNFα、IL6)的浓度。结果:两组患者术前血浆TNFα、IL6、CKMB浓度无差异,在主动脉阻断30分钟后已开始升高(P<0.05),实验组患者TNFα、IL6、CKMB在主动脉开放后各时间点血浆浓度均明显低于对照组(P<0.05)。结论:在CPB心脏冷停博液中加入腺苷注射液可明显减少CPB术中对心肌的损害,对术中肺保护起一定作用。