脑梗死患者血浆S100B蛋白测定的临床价值

目的探讨血浆S100B蛋白对脑梗死的诊断价值。方法采用酶联免疫吸附试验(ELISA)对39例脑梗死患者于起病第1、3、7、15天血浆S100B蛋白水平进行了动态测定。结果脑梗死患者血浆S100B蛋白在起病第1、3天显著高于正常对照组(P<0.01),第3天患者S100B蛋白水平上升达峰值,峰值浓度与梗死灶大小及临床预后有显著相关性;第15天下降至与正常对照组相同水平。结论S100B蛋白是一种神经胶质标志蛋白,其水平测定对判断脑梗死患者病变的严重程度、评估预后有重要参考价值。     

脑梗死患者血浆S100B蛋白测定的临床价值

目的探讨血浆S100B蛋白对脑梗死的诊断价值。方法采用酶联免疫吸附试验（ELISA）对39例脑梗死患者于起病第1、3、7、15天血浆S100B蛋白水平进行了动态测定。结果脑梗死患者血浆S100B蛋白在起病第1、3天显著高于正常对照组（P〈0．01）,第3天患者S100B蛋白水平上升达峰值,峰值浓度与梗死灶大小及临床预后有显著相关性;第15天下降至与正常对照组相同水平。结论S100B蛋白是一种神经胶质标志蛋白,其水平测定对判断脑梗死患者病变的严重程度、评估预后有重要参考价值。     

急性脑梗死患者血清S100β蛋白含量的变化及意义研究

目的探讨血清S100β蛋白对急性脑梗死(ACI)的诊断价值。方法采用酶联免疫吸附法(ELISA)对150例急性脑梗死患者和50例健康对照者血清S100β蛋白含量进行检测,观察比较不同病情和不同梗死面积ACI患者在不同时点含量的变化。结果 ACI患者12 h血清中的S100β蛋白含量高于健康对照组,差异有统计学意义(t=2.30,P<0.05);150例ACI重度、中度患者在入院后24、36、48、72 h血清S100β蛋白明显高于12 h轻度患者(P<0.05);150例ACI大面积、小面积患者在入院后24、36、487、2 h血清S100β蛋白明显高于12 h腔隙性梗死患者(P<0.05)。结论血清S100β蛋白可能是预测ACI患者病情严重程度及预后的重要指标之一。     

脑梗死患者恢复期脑组织血浆肿瘤坏死因子—α白介素—1β含量变化

目的：观察急性脑梗死患血浆肿瘤坏死因子－α（TNF－α）,白介素－1β（IL－1β）含量变化。方法：采用双抗体夹心（ELISA）法测量44例急性脑梗死患急性期,恢复期血浆TNFα,IL－β含量,并与40例正常对照组相比较。结果：急性期脑梗死患血浆TNF－α,IL－1β含量较恢复及其对照组均显增高,P＜0．01,恢复期TNF-α,IL-β含量虽明显下降,但较对照组为高,P＜0．01,二含量变化的关系与病情严重程度相一致。结论：急性脑梗死患存在神经－炎症／免疫－内分泌功能紊乱,两可能参与了脑梗死急性期的炎症反应及再灌注损伤。     

急性脑梗死患者血清IL-17、hs-CRP及TNF-α的动态变化及临床意义

目的观察急性脑梗死(ACI)患者血清白细胞介素(IL)-17、超敏C反应蛋白(hs-CRP)及肿瘤坏死因子-α(TNF-α)水平的动态变化,分析其与脑梗死体积及神经功能缺损程度的关系。方法选取ACI患者45例设为研究组,同期健康体检者35例为对照组,酶联免疫吸附法测定血清IL-17、hs-CRP及TNF-α水平。结果研究组入院后第1天,血清IL-17、hs-CRP及TNF-α水平显著高于对照组(P<0.01),随后逐渐下降,各时间点间差异显著,至第14天仍显著高于对照组(P<0.05,P<0.01);入院第7、14天脑梗死体积及NIHSS评分显著下降(P<0.01);血清IL-17在入院第1天与脑梗死体积、NIHSS评分正相关(P<0.05);hs-CRP、TNF-α水平在入院第1、7、14天均与脑梗死体积和NIHSS评分正相关(P<0.05或P<0.01)。结论 ACI患者血清IL-17、hs-CRP及TNF-α水平显著升高,呈现动态变化过程,且与脑梗死体积和神经功能缺损程度相关,可作为评估病情变化的参考指标。     

前列地尔对急性脑干梗死患者预后及血清IL-6、S100B及TNF?α水平的影响

目的探讨前列地尔对急性脑干梗死患者预后及血清白细胞介素-6(IL-6)、S100B及肿瘤坏死因子?α(TNF?α)水平的影响。方法选取82例急性脑干梗死患者,随机分为观察组和对照组,各41例。在常规治疗基础上,观察组静脉滴注前列地尔,对照组静脉滴注奥扎格雷钠,疗程2周。比较2组临床疗效,治疗前后美国国立卫生研究院卒中量表(NIHSS)和Barthel指数(BI)评分,治疗前及治疗第3、14天血清IL-6、S100B及TNF?α水平的变化,及不良反应情况。结果观察组临床总有效率显著高于对照组(P0.05)。治疗后,2组NIHSS评分较治疗前显著下降,而BI评分显著增加(P0.05或P0.01),其中观察组改善显著优于对照组(P0.01)。治疗后,2组血清IL-6、S100B及TNF?α水平均较治疗前有不同程度的下降,其中治疗第14天下降更为明显;观察组治疗第14天血清IL-6、S100B及TNF?α水平显著低于对照组(P0.01)。治疗期间,2组均未见严重不良反应发生。结论前列地尔可有效降低急性脑干梗死患者血清IL-6、S100B和TNF?α水平,减轻脑组织损伤,改善预后。     

血塞通对急性脑梗死患者外周血白细胞和血清S-100B蛋白的影响

目的观察血塞通对急性脑梗死(ACI)患者外周血白细胞(WBC)及血清S-100B蛋白含量的影响,探讨血塞通治疗脑梗死可能的作用机制。方法 118例ACI患者随机分成血塞通治疗组(A组)和对照组(B组)。B组予以常规的脱水、护脑治疗和丹参注射液治疗,A组在上述治疗基础上应用血塞通静脉注射。两组均于入院后6h、3d、8d、15d、30d等各时间点测定外周血WBC以及血清S-100B蛋白含量,并与10名健康成年人作为正常对照组比较,观察治疗后两组患者外周血WBC以及血清S-100B蛋白含量变化。结果①ACI患者外周血WBC计数以及血清S-100B蛋白含量明显高于正常对照组,差异有统计学意义(P<0.01),且增高的程度与患者临床神经功能缺损程度评分密切相关,评分越高WBC和S-100B蛋白含量越高。②ACI患者外周血WBC以及血清S-100B蛋白含量呈正相关(r=0.6837,P<0.01)。③30d后两组ACI患者外周血WBC以及血清S-100B蛋白含量均降低,但A组降低更明显,与B组比较具有显著性差异(P<0.05),而且出院时A组患者的疗效也优于B组。结论血塞通能降低ACI患者的外周血WBC以及血清S-100B蛋白含量,可能与血塞通减轻外周血WBC和S-100B蛋白介导的损伤性脑细胞炎症反应有关。     

阿尔茨海默病发病中β淀粉样蛋白40诱导白细胞介素-1α和S100β表达的意义

目的：探讨SD大鼠脑内β淀粉样蛋白40(amvloid-β protein 40，Aβ40)的沉积与细胞因子白细胞介素1α(IL-1α)、S100β表达的关系。方法：普通级SD雄性大鼠24只，单纯随机分为两组，各12只。Aβ40处理组将Aβ40定向微注射于大鼠的双侧海马CA1，CA2～CA3区，对照组用生理盐水处理。采用免疫组化方法观察了IL-1α和S100β的表达。结果：术后3，7d的IL-1α和S100β免疫组化均显示Aβ40处理组的大鼠海马区有细胞因子IL-1α，S100β的表达，而在生理盐水对照组的大鼠海马区未出现IL-1α，S100β的阳性表达。结论：Aβ40可诱导大鼠海马IL—1α和S100β表达。作为重要的病理性细胞因子，Aβ40诱导的细胞因子IL-1α和S100β上调表达可能具有重要的神经毒性效应，参与了阿尔苏海默病的病理活动。     

脑梗死患者血清中炎症细胞因子含量的变化与临床神经功能缺损程度的关系

目的：探讨脑梗死患者血清中炎症细胞因子含量的变化与临床神经功能缺损程度的关系。方法：将75例脑梗死组患者按照1995年中国脑中卒中患者临床神经功能缺损程度评分标准的评分结果分为轻度脑损伤（轻度）组，25例；中度损伤（中度）组，28例；重度损伤（重度）组，22例。选择同期健康体检正常者70例为对照组。检测两组血清肿瘤坏死因子-a（TNF-a）、白细胞介素-1B（IL-1B）、白细胞介素-6（IL-6）和C反应蛋白（CRP）的含量。结果：脑梗死组患者血清TNF—a、IL-1B、IL-6和CRP的含量，明显高于对照组（P值均〈0．001），脑梗死组中各亚组之间比较：重度组的含量分别高于中度组和轻度组（P〈0．05和〈0．01），中度组含量高于轻度组（P〈0．05），随着患者血清中炎症细胞因子含量的升高，患者的临床神经功能缺损程度评分（score）也增加，两者有显著的正相关关系。结论：脑梗死急性期存在炎症反应，检测血清TNF—a、IL-1B、IL-6和CRP的含量有助于脑梗死患者神经功能损伤程度的判断。其中CRP对神经功能损伤有独立的预测作用。     

急性脑梗死患者血清IL-1β、IL-8及TNF-α的临床意义

目的探讨急性脑梗死患者血清白细胞介素-1β(IL-1β)、白细胞介素-8(IL-8)及肿瘤坏死因子-α(TNF-α)水平的变化及其临床意义。方法用酶联免疫吸附测定(ELISA)检测187例急性脑梗死患者血清IL-1β、IL-8及TNF-α的水平,并与150例健康者进行比较。结果急性脑梗死患者不同梗死体积亚组血清IL-1β、IL-8及TNF-α水平均高于对照组,差异均有统计学意义(P0.05),并且随梗死体积的增加而增高。结论急性脑梗死患者血清IL-1β、IL-8及TNF-α水平增高,其升高的程度与梗死体积密切相关,可用于其病情评估、疗效监测和预后判断。     

Biological variation of interleukin-1beta, interleukin-8 and tumor necrosis factor-alpha in serum of healthy individuals.

Components of biological variation can be used to assess the usefulness of reference values, to evaluate the significance of changes in serial results from an individual and to define objective analytical goals. The aim of the study was to assess, in 15 healthy subjects studied at regular monthly intervals over a period of 6 consecutive months, the biological variation of interleukin-1beta (IL-1beta), interleukin-8 (IL-8), and tumor necrosis factor-alpha (TNF-alpha). Biological variation data (within-subject and between-subject coefficient of variation (CV)) were determined using a simple nested analysis of variance. Derived parameters (index of individuality, reliability coefficient and critical diferences) were calculated from within-subject and between-subject CV. The mean and standard deviation (SD), within-subject CV, between-subject CV, index of individuality and reliability coefficient were as follows: for IL-1beta, 0.67 (0.32) pg/ml, 30%, 36%, 0.85, and 0.76; for IL-8, 3.68 (1.45) pg/ml, 24%, 31%, 0.85 and 0.75; and for TNF-alpha, 3.14 (1.87) pg/ml, 43%, 29%, 1.56 and 0.50, respectively. We conclude that between-subject variation and within-subject variation are quite similar for IL-1beta and IL-8 and are relatively high for the three cytokines studied. Index of individuality is less than 1.4 for IL-1beta and IL-8, and thus reference intervals based on population studies are of limited value. On the contrary, the index of individuality for TNF-alpha is greater than 1.4 and reference values can be used for diagnosis. Quality goals for imprecision are easily achieved for the three cytokines with current methodology.     

Intra-abdominal sepsis alters tumor necrosis factor-alpha and interleukin-1 beta binding to human neutrophils.

OBJECTIVE: To determine the effects of intraabdominal sepsis on polymorphonuclear leukocyte tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 beta (IL-1 beta) receptor expression. DESIGN: Prospective, randomized comparison between patients undergoing elective colon surgery vs. patients with intra-abdominal sepsis. SETTING: Tertiary-care center with all patients with intra-abdominal sepsis in a surgical ICU environment. PATIENTS: Group 1 (n = 7) represents control patients who underwent elective colon surgery without intra-abdominal sepsis. Group 2 (n = 10) represents patients with intra-abdominal sepsis. MEASUREMENTS AND MAIN RESULTS: Polymorphonuclear leukocyte TNF-alpha and IL-1 beta receptor expression +/- stimulation of the oxidative burst was measured using 125I TNF-alpha and 125I IL-1 beta. Superoxide anion production and candicidal activity were measured in the presence of TNF-alpha and IL-1 beta. Group 2 patients expressed fewer TNF-alpha and IL-1 beta receptors on their cell surface, and stimulation of oxidative burst reduced TNF-alpha and IL-1 beta receptor expression in group 2 more than in group 1. Diminished TNF-alpha and IL-1 beta binding reduced superoxide anion production by group 2 polymorphonuclear leukocytes. Decreased TNF-alpha binding but not IL-1 beta, reduced polymorphonuclear leukocyte candicidal activity by group 2 polymorphonuclear leukocytes. CONCLUSIONS: a) Intra-abdominal sepsis reduces polymorphonuclear leukocyte TNF-alpha and IL-1 beta receptor expression. b) Expression of these surface receptors is altered by stimulation of the polymorphonuclear leukocyte oxidative burst. c) Diminished TNF-alpha and IL-1 beta receptor expression is associated with functional impairments in polymorphonuclear leukocyte activity.     

Circulating interleukin-1 beta and tumor necrosis factor-alpha concentrations after burn injury in humans.

OBJECTIVES: To measure plasma interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF alpha) concentrations after burn injury and to determine if these concentrations relate to clinical status. DESIGN: Prospective assessment. SETTING: Hospital burn unit. PATIENTS: Thirty-one patients with second- or third-degree burns, covering 10% to 95% of body surface area. MEASUREMENTS AND MAIN RESULTS: Initial concentrations of IL-1 beta were increased (mean 188 +/- 31 pg/mL), and the concentrations for each patient correlated with body temperature at the time of the blood sample (rho = 0.51, p < .015) (rho is a nonparametric statistical measure; a nonparametric analysis is mandatory for data that is categorical [Acute Physiology and Chronic Health Evaluation, APACHE, scores] and data that are not normally distributed [IL-1 beta and tumor necrosis factor, TNF, data]). Mean TNF alpha concentrations were initially 264 +/- 132 pg/mL, and these concentrations were positively related to body temperature (rho = 0.41, p < .05) and inversely related to the total WBC count (rho = -0.45, p < .025). Through the course of hospitalization, plasma cytokine levels fluctuated, but transient increases (sometimes into the nanogram/mL range) did not consistently correspond to changes in clinical signs or severity of illness, as determined by APACHE II scores. The maximum plasma cytokine levels in any patient were not related to age, but maximum IL-1 beta concentrations were inversely related to burn size (rho = -0.46, p < .015). The final IL-1 beta concentrations measured in the patients who died (n = 7) were significantly less than measurements in surviving patients matched for burn size and age taken at approximately the same time after admission. CONCLUSIONS: These results indicate that early after burn injury there is a correspondence of IL-1 beta and TNF alpha with certain host responses, but these correlations disappear with the progression of illness. In general, IL-1 beta and TNF alpha appear to be poor indicators of prognosis during burn injury; however, the association of mortality with low circulating IL-1 beta values supports the concept of IL-1 beta as being an essential mediator of host defenses.     

Tumour necrosis factor-alpha, interleukin-1beta and interleukin-8 induce persistent mechanical nociceptor hypersensitivity

It has been previously described that daily intraplantar (i.pl.) injections of prostaglandin E2 (PGE2) and dopamine in rats for 14 days cause the development of a persistent mechanical nociceptor hypersensitivity state lasting more than 30 days. Considering that during inflammation, the release of these hyperalgesic agents are mediated by cytokines, we investigated in the present study whether interleukin-1beta (IL-1beta), IL-8 and tumour necrosis factor-alpha (TNF-alpha) are able to induce persistent mechanical nociceptor hypersensitivity. Daily i.pl. administration of TNF-alpha, IL-1beta or IL-8 for 18 days led to persistent mechanical nociceptor hypersensitivity, which lasted at least 30 days after the cessation of treatment. The co-treatment of the animals with IL-1beta plus indomethacin, but not with atenolol, prevented the induction of persistent mechanical nociceptor hypersensitivity. The co-treatment of the animals with IL-8 plus atenolol, but not with indomethacin, prevented the induction of persistent mechanical nociceptor hypersensitivity. The daily co-treatment of TNF-alpha with either indomethacin or atenolol partially inhibited (+/-50%) the induction of persistent mechanical nociceptor hypersensitivity. However, the combined treatment with indomethacin plus atenolol abolished the induction of the persistent mechanical nociceptive hypersensitivity by TNF-alpha.A single injection of cytokines in the contralateral paws of the animals with persistent hypersensitivity caused only an acute nociceptive response. This observation, together with the demonstration of undetectable levels of immunoglobulins against TNF-alpha, IL-1beta or IL-8 in the sera of animals after the development of the persistent hypersensitivity induced by those cytokines, indicate that this event is not due to an ongoing immunological response against the cytokines. In conclusion, our results support the suggestion that IL-1beta- and IL-8-induced persistent mechanical nociceptor hypersensitivity results from the endogenous release of eicosanoids and sympathetic amines, respectively. However, TNF-alpha-induced mechanical nociceptor hypersensitivity results from the concomitant endogenous release of eicosanoids and sympathomimetic mediators.     

Cerebrospinal fluid tumor necrosis factor-alpha, interleukin-1beta, interleukin-6, and interleukin-8 as diagnostic markers of cerebrospinal fluid infection in neurosurgical patients

OBJECTIVE: To evaluate whether cerebrospinal fluid concentrations of tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, IL-6, or IL-8 may be used as diagnostic markers for the differential diagnosis of aseptic vs. bacterial meningitis and/or ventriculitis in neurosurgical patients. DESIGN: Prospective, observational study. SETTING: University teaching hospital. SUBJECTS: A total of 112 cerebrospinal fluid samples from 14 asymptomatic patients with normal cerebrospinal fluid after neurosurgery, 27 asymptomatic and 19 symptomatic patients with postneurosurgical aseptic meningitis, 32 patients with postneurosurgical cerebrospinal fluid infection, and 20 with severe subarachnoid and/or cerebral hemorrhage. MEASUREMENTS AND MAIN RESULTS: Specific ELISA kits were used to analyze TNF-alpha, IL-1beta, IL-6, and IL-8 concentrations on cerebrospinal fluid samples. Elevations in cerebrospinal fluid concentrations of TNF-alpha, IL-1beta, IL-6, and IL-8 were induced by different diseases or neurosurgical procedures, but cerebrospinal fluid bacterial infection induced the highest concentrations. To discriminate between aseptic cerebrospinal fluid pleocytosis and cerebrospinal fluid infection with a specificity of 95%, cerebrospinal fluid leukocyte count >1700/mL, TNF-alpha >150 pg/mL, and IL-1beta >90 pg/mL showed sensitivities of 51%, 74%, and 90%, respectively. Sufficiently sensitive and specific cutoff points could not be found for cerebrospinal fluid IL-6 or IL-8. CONCLUSION: Cerebrospinal fluid IL-1beta appears to be the best biochemical marker of cerebrospinal fluid infection in neurosurgical patients.     

Tumor necrosis factor-alpha and interleukin-1beta synergistically depress human myocardial function.

OBJECTIVE: Proinflammatory cytokines such as tumor necrosis factor (TNF)-alpha and interleukin (IL)-1beta have been implicated in the pathogenesis of myocardial dysfunction in ischemia-reperfusion injury, sepsis, chronic heart failure, viral myocarditis, and cardiac allograft rejection. Although circulating TNF-alpha and IL-1beta are both often elevated in septic shock, it remains unknown whether TNF-alpha or IL-1beta are the factors induced during sepsis that directly depress human myocardial function, and if so, whether the combination synergistically depresses myocardial function. Furthermore, the mechanism(s) by which these cytokines induce human myocardial depression remain unknown. We hypothesized the following: a) TNF-alpha and IL-1beta directly depress human myocardial function; b) together, TNF-alpha and IL-1beta act synergistically to depress human myocardial function; and c) inhibition of ceramidase or nitric oxide synthase attenuates myocardial depression induced by TNF-alpha or IL-1beta by limiting proximal cytokine signaling or production of myocardial nitric oxide (NO). DESIGN: Prospective, randomized, controlled study. SETTING: Experimental laboratory in a university hospital. SUBJECTS: Freshly obtained human myocardial trabeculae. INTERVENTIONS: Human atrial trabeculae were obtained at the time of cardiac surgery, suspended in organ baths, and field simulated at 1 Hz, and the developed force was recorded. After a 90-min equilibration, TNF-alpha (1.25, 12.5, 125, or 250 pg/mL for 20 mins), IL-1beta (6.25, 12.5, 50, or 200 pg/mL for 20 mins), or TNF-alpha (1.25 pg/mL) plus IL-1beta (6.25 pg/mL) were added to the bath, and function was measured for the subsequent 100 mins after the 20-min exposure. To assess the roles of the sphingomyelin and NO pathways in TNF-alpha and IL-1beta cross-signaling, the ceramidase inhibitor N-oleoyl ethanolamine (1 microM) or the NO synthase inhibitor N(G)-monomethyl-L-arginine (10 microM) was added before TNF-alpha (125 pg/mL) or IL-1beta (50 pg/mL). MEASUREMENTS AND MAIN RESULTS: TNF-alpha and IL-1beta each depressed human myocardial function in a dose-dependent fashion (maximally depressing to 16.2 + 1.9% baseline developed force for TNF-alpha and 25.7 + 6.3% baseline developed force for IL-1beta), affecting systolic relatively more than diastolic performance (each p < .05). However, when combined, TNF-alpha and IL-1beta at concentrations that did not individually result in depression (p > .05 vs. control) resulted in contractile depression (p < .05 vs. control). Inhibition of myocardial sphingosine or NO release abolished the myocardial depressive effects of either TNF-alpha or IL-1beta. CONCLUSIONS: TNF-alpha and IL-1beta separately and synergistically depress human myocardial function. Sphingosine likely participates in the TNF-alpha and IL-1beta signal leading to human myocardial functional depression. Therapeutic strategies to reduce production or signaling of either TNF-alpha or IL-1beta may limit myocardial dysfunction in sepsis.     

Plasma interleukin-1beta, -6, -8 and tumor necrosis factor-alpha as highly informative markers of pelvic inflammatory disease

BACKGROUND: The role of proinflammatory cytokines in pelvic inflammatory disease (PID) is unclear. We therefore determined whether plasma proinflammatory cytokines, interleukin-1beta (IL-1beta), IL-6, IL-8 and tumor necrosis factor-alpha (TNF-alpha) were useful plasma markers in PID patients. METHODS: Multiplex bead array analysis was used to measure the plasma levels of proinflammatory cytokines in 50 healthy controls as well as in 41 PID patients before and after routine protocol treatments. RESULTS: IL-1beta, IL-6, IL-8 and TNF-alpha were significantly elevated in PID patients before antibiotic treatment than after treatment. However, IL-8 was not significantly different between healthy controls and PID patients. The relative increase in ratio of IL-6 was significantly correlated with white blood cell count (r=0.448, p=0.003), neutrophil count (r=0.472, p=0.002) and C-reactive protein level (r=0.412, p=0.008). CONCLUSIONS: IL-1beta, IL-6, IL-8 and TNF-alpha may play an important role in the pathogenesis of PID. These biomarkers, particularly IL-6, could be useful adjuncts for the clinical diagnosis of PID.     

Transforming growth factor-beta1 blocks in vitro cardiac myocyte depression induced by tumor necrosis factor-alpha, interleukin-1beta, and human septic shock serum

OBJECTIVE: Serum from patients with septic shock induces depression of myocyte contractility in vitro that is proportional the reduction of ejection fraction in vivo. This effect is mediated, in part, by tumor necrosis factor (TNF)-alpha and interleukin (IL)-1beta. Transforming growth factor (TGF)-beta is an immunomodulatory cytokine with a broad range of anti-inflammatory effects. Using an in vitro assay, this study sought to determine the effect of TGF-beta1 on myocyte depression induced by TNF-alpha, IL-1beta, and serum with known depressant activity from patients with septic shock. DESIGN: The maximum extent of shortening of electrically paced rat cardiac myocytes in tissue culture was quantified by a closed-loop video tracking system. Myocytes were exposed to different combinations of TNF-alpha, IL-1beta, septic serum, and TGF-beta1. SETTING: Basic research laboratory. MEASUREMENTS AND MAIN RESULTS: Increasing concentrations of TNF-alpha and IL-1beta each caused significant depression of maximum extent of myocyte shortening in vitro over 30 mins (p<.0001). Similarly, a synergistic combination of TNF-alpha and IL-1beta as well as serum with known depressant activity from five patients with acute septic shock induced significant depression of cardiac myocyte contraction (p<.01). Increasing concentrations of TGF-beta1 alone had no effect on maximum extent of cardiac myocyte contraction. However, myocytes that were co-incubated with increasing concentrations of TGF-beta1 demonstrated dose-dependent reversal of depression induced by TNF-alpha or IL-1beta (p<.0001). Similarly, depressant effects caused by synergistic concentrations of TNF-alpha and IL-1beta and serum from all five patients with septic shock were prevented by co-incubation with TGF-beta1. CONCLUSIONS: These data demonstrate that depression of in vitro cardiac myocyte contraction induced by proinflammatory cytokines and septic serum can be blocked by TGF-beta1. TGF-beta1 may have potential as therapy for sepsis-associated myocardial depression in humans.     

血清肿瘤坏死因子-α水平与糖尿病肾病的关系

糖尿病肾病（diabetic nephropathy，DN）是糖尿病（diabetes mellitus，DM）的严重血管并发症之一，也是DM致死、致残的主要原因。国内外研究表明，DN的影响因素众多，其发生机制涉及糖、脂代谢紊乱，以及高血压、血液性状改变、细胞因子、遗传因素和环境因素等多方面。近年来研究结果显示，细胞因子和DN关系日益明确，肿瘤坏死因子-α（TNF-α）被认为是DM状态下多种生理、生化改变导致DN最后的共同中介物质，对DN等DM微血管病变具有多样性效应。笔者以不同临床期的DN患者作为病例组，以单纯2型DM患者作为对照组，探讨TNF-α对DN发生及临床进展的影响，以期指导临床及早期防治DN。