腹腔感染后白蛋白mRNA表达的变化及相关因素的作用

目的 探讨腹腔感染病人合并低白蛋白血症的机理。方法 以大鼠盲肠结扎穿孔（ＣＬＰ）为模型，观察ＣＬＰ后白蛋白ｍＲＮＡ表达的变化，并应用回归和相关方法，分析激素、细胞因子和内毒素的作用。结果 ＣＬＰ后白蛋白ｍＲＮＡ表达显著下降，并与血浆白蛋白浓度的变化密切相关，白蛋白ｍＲＮＡ的变化与门脉血内毒素明显相关，而与血中胰岛素、胰高糖素、胰高糖素／胰岛素比值、皮质醇、ＴＮＦ、ＩＬ－１和ＩＬ－６浓度的变化无明显     

杀菌/通透性增加蛋白对休克大鼠肺组织细胞因子mRNA表达的影响

作者在大鼠失血性休克（４ｋＰａ，１８０分钟）模型上，观察了重组杀菌／通透性增加蛋白（ＢＰＩ）对肺组织肿瘤坏死因子（ＴＮＦ）、白介素－６（ＩＬ－６）ｍＲＮＡ表达及急性肺损伤的影响，并对肠源性内毒素血症与炎症细胞因子诱发的关系进行了探讨。结果显示：失血性休克可导致血浆内毒素含量显著升高，肺组织ＴＮＦ、ＩＬ－６ｍＲＮＡ表达分别在复苏后２、８小时明显增多（Ｐ＜０．０５～０．０１）；给予ＢＰＩ治疗则完全中和休克所致内毒素血症，并不同程度地抑制肺组织ＴＮＦ、ＩＬ－６ｍＲＮＡ的表达（Ｐ＜０．０５～０．０１）；肺毛细血管通透性与髓过氧化物酶活性均明显降低。作者认为，ＢＰＩ可有效防止失血性休克诱发的急性肺损伤，其作用机制可能与抑制肠源性内毒素血症所介导的局部组织炎症细胞因子基因表达有关。     

杀菌／通透性增加蛋白对休克大鼠组织细胞因子mRNA表达的影响

作者在大鼠失血性休克模型上,观察了重组杀菌／通透性增加蛋白（ＢＰＩ）对肺组织肿瘤坏死因子（ＴＮＦ）、白人素－６（ＩＬ－６）ｍＲＮＡ表达及急性肺损伤的影响,并对肠源性内毒素血症与炎症细胞因子诱发的关系进行了探讨。结果显示：失血性休克可导致血浆内毒素含量显著升高,肺组织ＴＮＦ,ＩＬ－６ｍＲＮＡ表达分别在复苏后２、８小时明显增多（Ｐ〈０．０５－０．０１）;给予ＢＰＩ治疗则完全中和休克所致内毒素血症,并不     

烧伤并发内毒素血症早期肝损害与TNF-α mRNA表达的实验研究

目的观察ＴＮＦαｍＲＮＡ及其蛋白的组织分布和细胞定位,探讨烧伤并发内毒素血症早期肝损害的发生机理。方法选用２０％Ⅲ度ＴＢＳＡ烧伤大鼠合并腹腔内毒素（ＬＰＳ）注射造成烧伤复合内毒素血症肝损害模型,采用光镜,电镜及免疫组化原位杂交染色观察大鼠肝脏的形态功能变化、血清ＴＮＦα含量变化、肝组织ＴＮＦα和ＴＮＦαｍＲＮＡ的细胞定位及其分布。结果烧伤复合内毒素血症组,光镜下主要表现肝窦反应,枯否细胞（ＫＣｓ）激活与增生以及肝细胞（ＨＣｓ）变性坏死等;电镜下主要表现肝窦内血小板聚集、纤维素沉积与中性粒细胞（ＰＭＮｓ）扣押以及ＫＣｓ、肝细胞退变溶解等。血清丙氨酸氨基转氨酶（ＡＬＴ）显著升高（Ｐ＜０．０１）和白蛋白（ＡＬＢ）轻度下降。组织ＴＮＦα主要定位于肝窦内皮细胞（ＳＥＣｓ）、ＫＣｓ。ＴＮＦαｍＲＮＡ主要定位于ＫＣｓ、ＰＭＮｓ、巨噬细胞（ＭＰｓ）。而在单因素组主要特点为病变程度轻,肝功能损害不明显,血清ＴＮＦα峰值滞后以及组织ＴＮＦα和ＴＮＦαｍＲＮＡ表达相对较弱等。结论ＴＮＦα是参与烧伤复合内毒素血症早期肝脏损害的重要细胞因子。     

家兔创伤休克后血浆内毒素,TNF和IL—6的动态变化

目的：探讨创伤休克对内毒素移位的影响及其与ＴＮＦ、ＩＬ－６产生的关系。方法：选用家兔１６只，随机分为创伤合并失血性休克（Ⅰ组）和单纯失血性休克组（Ⅱ组），采用鲎试验基质显色法，ＥＬＩＳＡ和细胞生物测定法分别测定血浆内毒素、ＴＮＦ和ＩＬ－６水平。结果：休克１．５小时，Ⅰ组血浆内毒素水平即明显高于伤前，至复苏后０．５小时达峰值，复苏后１小时仍明显高于伤前。休克后Ⅰ组血浆内毒素水平明显高于Ⅱ组；休克及复苏后，血浆ＴＮＦ、ＩＬ－６水平也先后显著升高，其中ＴＮＦ升高较早，Ⅰ组血浆细胞因子水平明显高于Ⅱ组；相关分析表明，创伤休克后血浆ＴＮＦ、ＩＬ－６均值分别与血浆内毒素均值呈显著正相关。结论：创伤休克可导致明显的内毒素血症及ＴＮＦ、ＩＬ－６等细胞因子过量产生，且较单纯休克时明显，创伤后细胞因子产生与内毒素移位有一定的内在联系。     

山莨菪碱对创伤性肺损伤细胞因子及其mRNA表达的影响

目的 研究山莨菪碱（６５４－２）对创伤性急性肺损伤（ＡＬＩ）家兔血浆中肿瘤坏死因子－α（ＴＮＦ－α）、白细胞介素－６（ＩＬ－６）的含量及其在内脏组织中ｍＲＮＡ表达的影响。方法 用ＥＬＩＳＡ和ＲＴＰＣＲ方法测定２４只大耳白兔血ＴＮＦ－α、ＩＬ－６的含量及其在内脏组织中ｍＲＮＡ的表达。结果 创伤性ＡＬＩ家兔与正常组比较,血浆中ＴＮＦ－α、ＩＬ－６的含量升高,内脏组织中ＴＮＦ－α、ＩＬ－６ｍＲＮＡ的表达     

生长抑素和生长激素对急性坏死性胰腺炎肾损伤的保护作用

目的 实验性研究急性坏死性胰腺炎早期肾损伤的发病机制及生长激素和生长抑素的治疗作用。方法 经胰胆管逆行注射３．５％牛磺胆酸的２．５ｍｌ／ｋｇ建立大鼠ＡＮＰ模型,测定血淀粉酶、内毒素、ＩＬ－１、ＩＬ－６、ＩＬ－８和ＴＮＦ－α。观察肾病理变化和细胞超微结构发迹同时用ＲＴ－ＰＣＲ测定ＴＮＦ－αｍＲＮＡ表达的变化,探讨生长激素和生长抑素的疗效。结果 ＡＮＰ早期体内细胞因子和炎性介质过度升高,与肾损伤程度有     

己酮可可碱对内毒素肺损伤肺组织TNFmRNA表达的影响

目的：观察己酮可可碱对内毒素血症引起的肺组织ＴＮＦｍＲＮＡ表达及血浆ＴＮＦ的影响。方法：选用ＳＤ大鼠６３只，分三组：①生理盐水组（Ｃ组）；②内毒素组（Ｅ组），大肠杆菌Ｏ５５Ｂ５内毒素１５ｍｇ／ｋｇ静注；③内毒素＋己酮可可碱组（Ｅ＋Ｐ组），１５ｍｇ／ｋｇ内毒素加２０ｍｇ／ｋｇ己酮可可碱静注，６ｍｇ／ｋｇ己酮可可碱维持。每组分１、３、６小时三个时间点，用差别聚合酶链反应测定肺组织ＴＮＦｍＲＮＡ的变化，双抗体夹心法测定血浆ＴＮＦ的变化。结果：内毒素组血浆ＴＮＦ在１小时达高峰，３小时仍升高，６小时接近生理盐水组水平，己酮可可碱组１小时和３小时血浆ＴＮＦ与相应内毒素组比明显下降（Ｐ分别＜０．０１，０．０５）；ＴＮＦｍＲＮＡ表达在内毒素组１小时和３小时明显升高，己酮可可碱治疗后ＴＮＦｍＲＮＡ表达和内毒素组比明显下降（Ｐ＜０．０１），己酮可可碱组病理损害明显减轻。结论：ＴＮＦ是一个早期的重要炎症介质，己酮可可碱能抑制ＴＮＦ的产生，通过抑制其转录而产生作用，己酮可可碱对内毒素肺损伤具有保护作用。     

地塞米松对创伤性急性肺损伤家兔肿瘤坏死因子-α的干预作用

目的 探讨地塞米松（Ｄｅｘ）对创伤性急性肺损伤（ＡＬＩ）治疗作用的可能机制。方法 采用逆转录聚合酶链反应（ＲＴ－ＰＣＲ）、酶联免疫吸附法（ＥＬＩＳＡ）检测２４只大耳白兔肺组织肿瘤坏死因子－α基因（ＴＮＦ－αｍＲＮＡ）表达及肺泡巨噬细胞（ＡＭ）培养上清液中肿瘤坏死因子－α（ＴＮＦ－α）、白细胞介素（ＩＬ）－６水平。结果 创伤性ＡＬＩ兔肺组织ＴＮＦ－αｍＲＮＡ表达及ＡＭ培养上清液中ＴＮＦ－α,ＩＬ－６含量较正常对照组比较明显升高（Ｐ〈０．０１）。Ｄｅｘ治疗后能显著下调ＴＮＦ－αｍＲＮＡ的表达（６８％,Ｐ〈０．０１）,降低ＡＭ分泌ＴＮＦ－α（Ｐ〈０．０５）及ＩＬ－６水平（Ｐ〈０．０１）。结论 Ｄｅｘ能缓解创伤性ＡＬＩ的发生、发展。其机制与其对ＴＮＦ－α、ＩＬ－６等炎性介质的调节作用密切相关。     

生长抑素和生长激素联合应用治疗重症急性胰腺炎的临床研究

目的 探讨生长抑素和生长激素联合应用治疗重症急性胰腺炎（ＳＡＰ）的疗法。方法 对３２例ＳＡＰ，随机分为生长抑素治疗组（ｎ＝１１），生长激素和生长抑素联合应用治疗组（ｎ＝１０）以及对照组（ｎ＝１１）。观察各组治疗后血清ＩＬ－１，ＩＬ－６和ＴＮＦα的变化，住院日数，并发症和死亡率。结果 生长 抑素和生长激素联合组能冯少并发症，降低死亡率，缩短住院日数，抑制ＳＡＰ病人的炎性细胞因子高表达，促进白蛋白合成     

Increased albumin and fibrinogen synthesis rate in patients with chronic renal failure

BACKGROUND: Hypoalbuminemia and hyperfibrinogenemia are frequently observed in patients with chronic renal failure (CRF) and are both associated with cardiovascular diseases. The mechanisms responsible for hypoalbuminemia and hyperfibrinogenemia in CRF are unknown. METHODS: In the present study, both albumin and fibrinogen kinetics were measured in vivo in predialysis patients (N = 6), patients on peritoneal dialysis (N = 7) and control subjects (N = 8) using l-[1-13C]-valine. RESULTS: Plasma albumin concentration was significantly lower in patients on peritoneal dialysis compared to control subjects (P < 0.05). Plasma fibrinogen was significantly increased in both predialysis patients (P < 0.01) as well as patients on peritoneal dialysis (P < 0.001) in comparison to control subjects. In contrast to albumin, fibrinogen is only lost in peritoneal dialysate and not in urine. The absolute synthesis rates (ASR) of albumin and fibrinogen were increased in patients on peritoneal dialysis (ASR albumin, 125 +/- 9 mg/kg/day versus 93 +/- 9 mg/kg/day, P < 0.05; ASR fibrinogen, 45 +/- 4 mg/kg/day versus 29 +/- 3 mg/kg/day, P < 0.01) compared to control subjects. Albumin synthesis is strongly correlated with fibrinogen synthesis (r2 = 0.665, P < 0.0001, N = 21). In this study, the observed hypoalbuminemia in patients on peritoneal dialysis is likely not explained by malnutrition, inadequate dialysis, inflammation, metabolic acidosis, or insulin resistance. We speculate that peritoneal albumin loss is of relevance. CONCLUSION: Synthesis rate of albumin and fibrinogen are coordinately up-regulated. Both albumin and fibrinogen are lost in peritoneal dialysis fluid. To compensate protein loss, albumin synthesis is up-regulated, but the response, in contrast to predialysis patients, does not fully correct plasma albumin concentrations in peritoneal dialysis patients. The increase in fibrinogen synthesis introduces an independent risk factor for atherosclerosis, since plasma fibrinogen pool is enlarged.     

Relationships among inflammation nutrition and physiologic mechanisms establishing albumin levels in hemodialysis patients

BACKGROUND: Serum albumin concentration is a balance among its synthesis rate, fractional catabolic rate (FCR), distribution, dilution in the plasma pool and external loss. The physiologic bases for establishing the level of serum albumin in hemodialysis patients have not been defined despite the association of hypoalbuminemia with excess mortality. Albumin concentration is associated with the levels of several acute phase proteins (APPs), C-reactive protein (CRP), alpha1 acid glycoprotein (alpha1 AG), or ceruloplasmin, and with nutritional markers, such as normalized protein catabolic rate (nPCR). METHODS: To establish the relationship among parameters that regulate albumin levels and markers of nutrition and inflammation, we injected [125I]-albumin, into 64 hemodialysis patients enrolled in the HEMO study to measure albumin distribution, synthesis and FCR. These variables were related to the levels of acute phase proteins (APPs), nPCR, body mass index (BMI), external albumin loss as well as demographic variables. Albumin distribution, synthesis and FCR were calculated from kinetic modeling, as was the initial plasma volume (PV). Serum albumin, transferrin, CRP, ceruloplasmin and alpha1 AG were measured weekly. Dialysate was collected during one dialysis each week to measure albumin loss. Results were analyzed by multiple linear regression. RESULTS: Albumin concentration correlated with its synthesis rate and FCR, but not with PV or its distribution between the vascular and extravascular pools. Albumin concentration also correlated with nPCR and alpha1 AG. However, albumin synthesis was directly related most strongly to PV and BMI (or nPCR), but not to levels of APPs. By contrast, albumin FCR correlated positively with both alpha1 AG and ceruloplasmin. CONCLUSION: Albumin concentration in dialysis patients changes with inflammation and nutritional status through their effects on albumin catabolism and synthesis, respectively. Within the range of albumin levels in these patients, nutritional variables primarily affected albumin synthesis while inflammation caused hypoalbuminemia by increasing albumin FCR. Albumin synthesis also increased in proportion to PV. The result of this is that PV expansion does not contribute to hypoalbuminemia.     

A New Application for Albumin Dialysis in Extracorporeal Organ Support: Characterization of a Putative Interaction Between Human Albumin and Proinflammatory Cytokines IL‐6 and TNFα

Albumin dialysis in extracorporeal organ support is often performed in the treatment of liver failure as it facilitates the removal of toxic components from the blood. Here, we describe a possible effect of albumin dialysis on proinflammatory cytokine levels in vitro. Initially, albumin samples were incubated with different amounts of cytokines and analyzed by enzyme‐linked immunosorbent assay (ELISA). Analysis of interleukin 6 (IL‐6) and tumor necrosis factor alpha (TNFα) levels indicated that increased concentrations of albumin reduce the measureable amount of the respective cytokines. This led to the hypothesis that the used proinflammatory cytokines may interact with albumin. Size exclusion chromatography of albumin spiked with cytokines was carried out using high‐performance liquid chromatography analysis. The corresponding fractions were evaluated by immunoblotting. We detected albumin and cytokines in the same fractions indicating an interaction of the small‐sized cytokines IL‐6 and TNFα with the larger‐sized albumin. Finally, a two‐compartment albumin dialysis in vitro model was used to analyze the effect of albumin on proinflammatory cytokines in the recirculation circuit during 6‐h treatment. These in vitro albumin dialysis experiments indicated a significant decrease of IL‐6, but not of TNFα, when albumin was added to the dialysate solution. Taken together, we were able to show a putative in vitro interaction of human albumin with the proinflammatory cytokine IL‐6, but with less evidence for TNFα, and demonstrated an additional application for albumin dialysis in liver support therapy where IL‐6 removal might be indicated.     

Albumin synthesis rates are not decreased in hypoalbuminemic cachectic cancer patients with an ongoing acute-phase protein response.

OBJECTIVE: To determine whether suppression of albumin synthesis contributes to the hypoalbuminemia observed in weight-losing cancer patients with evidence of an ongoing acute-phase protein response (APPR). BACKGROUND DATA: Proinflammatory cytokines such as tumor necrosis factor (TNF) and interleukin 6 (IL-6) are known to downregulate albumin synthesis and increase acute-phase protein production in isolated hepatocytes. However, whether albumin synthesis is suppressed in hypoalbuminemic cancer patients with evidence of an ongoing acute-phase response is unknown. METHODS: Albumin synthesis rates were determined in six healthy controls and in six weight-losing pancreatic cancer patients with an ongoing APPR using a flooding dose technique with [2H5]-phenylalanine. The presence of an APPR was defined as a serum C-reactive protein concentration >10 mg/L. Serum cytokines (TNF, IL-6) and soluble TNF receptors (sTNF-R 55 and 75), along with serum cortisol and insulin, were also measured in both groups. RESULTS: Cancer patients had reduced serum albumin (median 32 [range, 23-36] vs. 42 g/L [40-45]; p < 0.01) and increased serum C-reactive protein concentrations (72 [23-126] vs. <5 mg/L; p < 0.01) when compared with controls. TNF was not detected in either group. sTNF-R 55 levels were significantly elevated in the cancer patients (3.8 [1.9-8.1] vs. 1.2 pg/mL [0.9-2.2]; p < 0.01). Circulating IL-6, insulin, and cortisol concentrations were not significantly different between the groups. The intravascular albumin mass was lower (88 [56-93] vs. 133 g [105-177]; p < 0.01), but the intravascular albumin fractional synthetic rate was higher (13.9 [13.5-18.5] vs. 10.3%/d [71-11.3]; p < 0.01) in the cancer patients compared with the controls. The total intravascular albumin synthetic rate was, however, similar between the two groups (12.7 [7.7-15.7] vs. 11.7 g/d [8.5-18.7]; p NS). CONCLUSIONS: In weight-losing pancreatic cancer patients with evidence of an ongoing APPR, hypoalbuminemia is not caused by a decreased rate of albumin synthesis.     

重组生长激素对严重感染后蛋白质代谢影响的实验研究

本文旨在探讨重组生长激素对腹腔严重感染后蛋白质代谢的影响及其作用机制。作者以大鼠盲肠结扎穿孔复制严重感染模型，并将其分为治疗组和感染组，分别于术后给予生长激素（ｒＧＨ）和生理盐水，进行观察研究。结果显示：（１）ｒＧＨ促进正氮平衡恢复，提高了血浆白蛋白水平；（２）ｒＧＨ促进肠粘膜谷氨酰胺利用酶活性的恢复，维持了肠粘膜正常形态结构，降低了门脉内毒素含量和循环ＴＮＦ水平；（３）ｒＧＨ直接促进了离体肝细胞合成白蛋白，感染时提高受抑的白蛋白ｍＲＮＡ表达水平。结果表明，ｒＧＨ可促进感染后肠粘膜对谷氨酰胺的利用，维持粘膜正常结构和功能，减轻了肠源性高代谢反应。同时，从分子水平揭示ｒＧＨ直接刺激肝细胞白蛋白ｍＲＮＡ的表达，促进了感染时白蛋白的合成，有利于正氮平衡的恢复，提高了生存率。     

重组生长激素对严重感染后蛋白代谢影响的实验研究

本文旨在探讨重组生长激素对腹腔严重感染后蛋白质代谢的影响及其作用机制。作者以大鼠讯肠结扎穿孔复制严重感染模，并将其分为治疗组和感组，分别于术后给予生长激素和生理盐水，进行观察研究。     

Factors that affect albumin concentration in dialysis patients and their relationship to vascular disease

INTRODUCTION: Hypoalbuminemia is a powerful risk factor for cardiovascular mortality in hemodialysis patients (HD). Inflammation causes a decrease in albumin synthesis and an increase in albumin fractional catabolic rate, providing two mechanisms for hypoalbuminemia. The inflammatory response alters the endothelium and plasma protein composition in ways that favor vascular injury. Plasma volume is expanded in HD patients, providing another mechanism for hypoalbuminemia. Fibrinogen levels are an independent risk factor for cardiovascular disease (CVD) in HD patients, and fibrinogen levels are increased in HD patients. Plasma volume expansion is also an independent risk factor for CVD. METHODS: Albumin synthesis was measured in 74 HD patients as the disappearance of [125I] human albumin over six weeks. Fibrinogen was measured in plasma. Plasma fibrinogen mass was the product of fibrinogen concentration and plasma volume. RESULTS: Albumin synthesis correlated positively with plasma volume (P < 0.001). Fibrinogen concentration and plasma fibrinogen mass both correlated positively with albumin synthesis (P < 0.001). CONCLUSION: Albumin levels are reduced as part of the acute-phase response in HD. Plasma volume expansion also tends to decrease albumin concentration, but elicits an increase in its rate of synthesis, which, in turn, is associated with increased fibrinogen levels. Thus, both inflammation and plasma volume expansion factors that reduce albumin concentration and are independent cardiovascular risk factors, independently increase fibrinogen levels.     

Immunoprotective effect of a calcium channel blocker on macrophage antigen presentation function, major histocompatability class II antigen expression, and interleukin-1 synthesis after hemorrhage

Hemorrhage induces a severe suppression of the immune system resulting in increased susceptibility to sepsis. Although studies indicate beneficial effects of calcium channel blockers on cell and organ functions after low-flow conditions, it remains unknown whether such agents have any effects on different immune responses after hemorrhage. To study this, C3H/HeN mice were bled to a mean blood pressure of 35 mm Hg and were maintained for 60 minutes, followed by resuscitation with their own shed blood and adequate fluid. The mice received either the water-soluble calcium channel blocker diltiazem (400 or 2400 micrograms/kg body weight) or saline solution (vehicle). Peritoneal macrophages were obtained by lavage 24 hours later. Antigen presentation was measured by coculturing peritoneal macrophages with the D10.G4.1 helper T-lymphocyte clone. Immune associated antigen (Ia) expression was determined by direct immunofluorescence. Interleukin (IL)-1, 6, and tumor necrosis factor-alpha (TNF) levels in peritoneal macrophage supernatants were measured by use of cytokine-specific cellular assays. Hemorrhage caused a significant decrease in peritoneal macrophage antigen presentation function, Ia expression, and IL-1 and IL-6 synthesis in the vehicle-treated group, whereas TNF levels were increased. However, both doses of diltiazem significantly improved peritoneal macrophage antigen presentation, Ia expression, and IL-1 synthesis. IL-6 synthesis was only increased with high doses of diltiazem, whereas both diltiazem doses decreased TNF production. These results indicate that the calcium channel blocker diltiazem can markedly improve macrophage functions after hemorrhage. The use of diltiazem might offer a new therapeutic modality in the treatment of immunosuppression and in decreasing the susceptibility to sepsis after hemorrhagic shock.     

严重烧伤后小鼠腹腔巨噬细胞（Mφ）CD14表达的变化

目的 探讨烧伤后早期腹腔Mφ CD14分子的动态变化。方法 采用小鼠20％TB-SAⅢ度烧伤模型，分离和培养小鼠腹腔Mφ，用免疫组织化学、RT—PCR和ELISA方法，观察了烧伤复苏组和延迟复苏组伤后24h内不同时间腹腔Mφ表达CD14和CD14 mRNA、分泌肿瘤坏死因子(TNF)和白介素-6(IL-6)的变化。结果 烧伤复苏组和延迟复苏组在伤后1h腹腔Mφ表达CD14和分泌TNFα、IL-6明显增加，这种改变在伤后24h内持续。结论烧伤能增加Mφ CD14 mRNA的表达，从而使Mφ易于被很低浓度内毒素(LPS)激活，Mφ的致敏和激活使其在伤后过度炎症反应的发生发展中起重要作用。