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1.
The release of inflammatory cytokines caused by a disrupted disc may play a critical role in pain production at nerve endings, axons, and nerve cell bodies. Herniated disc tissue has been shown to release inflammatory cytokines such as interleukin-1 beta (IL-1beta), interleukin-6 (IL-6), tumor necrosis factor (TNF), and other algesic chemicals. This study was designed to characterize the effects of these proinflammatory cytokines on the somatosensory neural response at the dorsal root level in rats. It is hypothesized that their effects on nerve endings in disc and adjacent tissue contribute to low-back pain, and the effects on dorsal root axons and ganglia contribute to radiculopathy and sciatica. Surgically isolated sacral dorsal roots were investigated by electrophysiologic techniques. IL-1beta, IL-6, or TNF (100 ng, each) were applied onto the dorsal roots. Neural responses and mechanosensitivity of the receptive fields were evaluated over time. The results showed that 3 h after each cytokine application, the neural activity was statistically decreased. The mechanical sensitivity of the receptive fields increased at 90 min following IL-1beta or TNF application, and returned to normal more than 3 h after IL-1beta application. IL-1beta, IL-6, and TNF may be neurotoxic to dorsal root axons. Furthermore IL-1beta and TNF may sensitize the peripheral receptive fields. This study suggests that dorsal roots may be impaired by these proinflammatory cytokines.  相似文献   

2.
Kupffer cells, when activated, release toxic cytokines such as tumor necrosis factor (TNF), which can cause tissue injury. Takei et al. have reported that nisoldipine, a calcium channel blocker which decreases phagocytotic activity by Kupffer cells, also diminishes liver and lung injury and dramatically improves survival following liver transplantation [27]. Therefore, we studied the effect of nisoldipine on the time course of TNF and interleukin-6 (IL-6) release following cold storage and liver transplantation in the rat. Livers were stored under survival and non-survival conditions in cold Euro-Collins solution in the presence or absence of nisoldipine (1.4 µM). After storage, the effluent was collected for determination of cytokines. The liver was then transplanted orthotopically and serum was collected at various time intervals for up to 5 h. In the effluent, TNF levels were very low in both the control and nisoldipine-treated groups and IL-6 was not measurable. Furthermore, when livers were stored under survival conditions and transplanted (liver stored in the cold for 4 h), serum TNF (2 U/ml) and IL-6 (350 U/ml) values were minimal in both the control and nisoldipine-treated groups. In contrast, when livers were stored under non-survival conditions and transplanted (liver stored in the cold for 10 h), TNF levels increased to 15 ± 2 U/ml, 150 min after graft reperfusion, an increase which was prevented by nisoldipine (6.5 U/ml). Serum IL-6 levels were also elevated 300 min after transplantation in livers stored for 10 h. Nisoldipine also reduced the release of this cytokine. Serum transaminases (SGOT) were elevated to values around 2000 U/l 5 h following transplantation. In the nisoldipine-treated group, values were lower between 60 and 300 min. In the lung, interstitial and alveolar edema and cellular infiltration were detectable 5 h post-operatively and were diminished by nisoldipine. These data confirmed that TNF and IL-6 release were minimal following cold storage and transplantation of livers stored under survival conditions, but were elevated transiently after transplantation under non-survival conditions. Nisoldipine prevented cytokine release, most likely by blocking the activation of Kupffer cells, which may explain how it decreases liver and lung injury very early following liver transplantation.  相似文献   

3.
Background: The cellular basis for augmented cytokine production in the tumor-bearing host is not known. Recently leukemia inhibitory factor (LIF) and interleukin (IL)-6, produced by a variety of tumors, have been implicated as mediators of cachexia. Methods: Five murine tumor cell lines were tested for the production of these cytokines. 4JK tumor was further tested to determine if IL-1, tumor necrosis factor (TNF), or cocultivation with RAW 264 cells augmented IL-6 or LIF production. Results: 4JK from in vivo tumors produced significantly more IL-6 than did 4JK from culture, indicating that tumor production of IL-6 and LIF is potentially augmented by infiltrating macrophages. When 4JK was cocultured with RAW 264 cells, TNF, or IL-1 in vitro, a three- to 15-fold increase in tumor production of LIF and IL-6 was noted (p2⩽0.03). Conversely, in coculture experiments performed with a neutralizing TNF antibody, a 50% reduction in tumor production of LIF and IL-6 was noted (p2<0.04). Resting RAW cells produced only minimal quantities of TNF; however, when RAW cells were exposed to tumor-conditioned supernatant from 4JK, their TNF production was markedly increased. Conclusions: In the tumor microenvironment, host macrophages may be activated and produce inflammatory cytokines such as TNF. Local TNF then appears to act on tumor cells to stimulate production of IL-6 and LIF. Enhanced tumor production of cytokine mediators may contribute to deleterious effects of neoplastic growth on the host. Presented at the 47th Annual Cancer Symposium of The Society of Surgical Oncology, Houston, Texas, March 17–20, 1994.  相似文献   

4.
This study was designed to characterize the effects of low doses (0.5–5 ng) of pro-inflammatory cytokines, interleukin-1 beta (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor (TNF), on the neural activity of dorsal root ganglion (DRG) in rats. The purpose of this study was to examine the effects of cytokines (IL-1β, IL-6, and TNF) on the somatosensory neural response of DRG. The release of inflammatory cytokines by an injured disc may play a critical role in pain production at nerve endings, axons, and nerve cell bodies. Herniated disc tissue has been shown to release IL-1β, IL-6, TNF, and other algesic chemicals. Their effects on nerve endings in disc and adjacent tissue may lead to low back pain and their effects on dorsal root axons and ganglia may lead to sciatica. Exposed lumbar DRGs were investigated by electrophysiologic techniques. Sham (mineral oil), control (carrier solution), or IL-1β, IL-6, or TNF at doses of 0.5, 1, and 5 ng were applied over the DRG. Baseline discharge rates as well as mechanosensitivity of the DRG and peripheral receptive fields were evaluated over 30 min. Applications of IL-1β at 1 ng resulted in an increase in the discharge rate, 5 ng resulted in an increased mechanosensitivity of the DRG in group II units. Similarly, after 1 ng TNF applications, group II units also showed an increase in mechanosensitivity of DRG and peripheral receptive fields. At low doses IL-1β and TNF sensitization of receptive fields were observed. The responses observed in the group II units indicate that a sub-population of afferent units might have long-term effects modifying the sensory input to the central nervous system. This study provides added evidence to the role of cytokines in modulating afferent activity following inflammation.  相似文献   

5.
体外循环心脏手术中骨骼肌TNF-α和IL-8 mRNA表达的变化   总被引:1,自引:0,他引:1  
目的 观察体外循环(CPB)心脏手术期间腹直肌TNF-α IL-8 mRNA表达的变化。方法 选择10例风湿性心脏病瓣膜置换术患者,分别于劈胸骨和关胸时在胸部正中切口下缘取腹直肌2g,用Tizol试剂提取总RNA,以RT-PCR测定TNF-α、IL-8 mRNA表达量,并分别在麻醉前、劈胸骨、CPB15 min、开放升主动脉后5 min、关胸时取静脉血以酶联免疫放射法测定TNFα和IL-8的含量。结果与劈胸骨时相比较,关胸时患者TNF-α、IL-8 mRNA表达明显增强(P<0.05),CPB 15min、开放升主动脉后5min、关胸时患者血TNF-α、IL-8水平明显高于麻醉前(P<0.05)。结论 体外循环中患者骨骼肌TNF-α、IL-8 mRNA表达明显升高,血TNF-α、IL-8含量也增高,这些变化可能在CPB期间全身炎性反应中起重要作用。  相似文献   

6.
Objective: To study the changes of interleukin-1 β(IL-1β), tumor necrosis factor α (TNFα) and interleukin-6 (IL-6) levels in brain and plasma after brain injury and to assess the relationship between the cytokine levels and injury severity in rats. Methods. A total of 51 male Wistar rats, weighing 280-340g, were anesthetized with chloral hydrate(400 mg/kg body weight) through intraperitoneal injection and fixed on a stereotaxic instrument. Severe brain injury was created in 16 rats (severe injury group) and moderate brain injury in 18 rats (moderate injury group) by a fluid percussion model, and cytokine levels of IL-1β, TNFα and IL-6 were measured with biological assay. And sham operation was made on the other 17 rats (control group). Results: In the control group, the levels of IL-1β,TNFα and IL-6 were hardly detected in the cortex of the rats, but in the ipsilateral cortex of the rats in both injury groups, they increased obviously at 8 hours after injury.The increasing degree of these cytokines had no significant difference between the two injury groups. The levels of IL-6 in the plasma of all the rats increased slightly, whereas the levels of IL-1β and TNFα were undetectable. Conc|usions: The increase of IL-1β, TNFα and IL-6 levels is closely related to brain injury. The increased cytokine levels in the central nervous system are not parallel to those in the peripheral blood. It suggests that inflammatory cytokines play important roles in the secondary neural damage after brain injury.  相似文献   

7.
背景 肺损伤是心脏手术体外循环(cardiopulmonary bypass,CPB)的主要并发症之一,肺保护一直是临床、实验研究热点.目的 为CPB下心脏手术肺保护提供参考.内容 就近年来心脏手术CPB期间通气策略和麻醉药物、CPB设备和技术、肺动脉灌注技术、药物干预对肺保护作用的进展进行综述.趋向 CPB下心脏手术...  相似文献   

8.
contributiontothetreatmentofdeepandextensiveburns.ThedoctorsintheBurnUnitofShanghaiRuijinHospitalhavemadeamodificationintheperformanceofthesocalled“alternatestrip”methodintroducedbyJackson.Sincethen,manypatientswithmorethan50%thirddegreeburnshavebeentre…  相似文献   

9.
Objective To investigate the incidence and to evaluate the risk factors of acute kidney injury (AKI) following cardiac surgery with cardiopulmonary bypass (CPB) at general hospitals. Methods A retrospective cohort database study was conducted, involving 233 patients who were scheduled to heart valve surgery or coronary artery bypass grafting (CABG) with CPB technique. Logistic regression was used to screen out the risk factors of AKI after the surgery. Results The study population, with an average age of 57±12 years (age 21 to 83) were investigated, there were 54(23.2%) diabetes patients, 105 (45.1%) hypertension patients, 21 (9%) chronic kidney disease (CKD) patients, and 51 (21.9%) anemia patients. Overall incidence of AKI was 32.2%. The Analysis Result indicates that preoperative CKD, anemia, hypoalbuminemia, left ventricular ejection fraction, intraoperative aortic block time, minimum mean arterial pressure, perioperative infection, and application of vancomycin are risk factors associated with postoperative AKI. Multiariable Logistic regression suggests that basic CKD (OR=9.498, P=0.001), anemia (OR=3.150, P=0.021), the LVEF before surgery (OR=1.733, P=0.045), intraoperative aortic block time (OR=2.227, P=0.026), and white blood cell (OR=3.357, P=0.032) were the independent risk factors of AKI. Conclusions AKI is a common complication following cardiac surgery with CPB. The patients with preoperative renal insufficiency, anemia, long intraoperative aortic block time and higher perioperative white blood cell count are subjected to a higher incidence of AKI. Alleviating patients’ anemia and reducing artery block of extracorporeal circulation time therefore might be potential means to mitigate the risks of AKI after cardiac surgery.  相似文献   

10.
目的 探讨心肺转流(CPB)对血管内皮细胞(VEC)功能和肿瘤坏死因子α(TNF-α)的影响. 方法 24例择期手术的先天性心脏病患者,分为两组:A组(n=14)在CPB下行心内直视手术;B组(n=10)在非CPB下行心内直视手术.于麻醉前(T1)、术毕(T2)、术后6(T3)、24 h(T4)采集桡动脉血,测定血浆中NO-2/NO-3、内皮素-1(ET-1)、丙二醛(MDA)和TNF-α的水平.结果 与B组比较,A组ET-1水平在T2和T3时点明显升高(P<0.01),到T4时恢复术前水平;A组T2时点血浆NO-2/NO-3水平明显低于B组(P<0.05).A组T2、T3时MDA浓度均高于B组(P<0.05).与术前相比,A组血浆TNF-α浓度在T2~T4时均持续升高(P<0.01).结论 CPB可致VEC功能活化,使血浆ET-1/NO平衡失调.  相似文献   

11.
体外循环中抗肿瘤坏死因子抗体的肺保护作用   总被引:1,自引:0,他引:1  
目的 探讨抗肿瘤坏死因子抗体(TNF-α Ab)对体外循环(CPB)肺损伤的保护作用。方法 选择CPB瓣膜置换病人20例,随机分为对照组和用药组各10例。用药组于CPB前和主动脉开放后即刻经气管插管注入TNF-αAb。测定两组围CPB期肺动态顺应性,左、右心房血中性粒细胞计数、肿瘤坏死因子(TNF-α)含量等指标。结果 用药组CPB后各时点肺动态顺应性显著高于对照组;TNF—αAb明显抑制肺源性TNF(COB)-α的释放及中性粒细胞在肺内的聚集。结论 预防性应用TNF-αAb对体外循环肺损伤有明显的保护作用。  相似文献   

12.
目的探讨肿瘤坏死因子(TNF)和可溶性肿瘤坏死因子受体(STNFR)与膀胱肿瘤生物学行为的关系。方法测定26例膀优移行细胞癌患者和20例正常对照者血清中TNF和STNFR水平。结果发现膀胱肿瘤患者血TNF水平与对照组相比差异无显著性(P>0.05),而STNFR水平显著高于对照组(P<0.001),并随着临床分期的增加而升高,巨术后2周时显著下降(P<001);TNF与STNFR水平之间无显著相关关系。结论STNFR抑制了TNF生物学活性而降低了机体的免疫功能,并可作为评估病情严重程度和预后的指标。  相似文献   

13.
Purpose The Sonoclot Analyzer provides a functional test of whole blood coagulation by measuring the viscous property of the blood sample. In this study, we used a modified Sonoclot assay, using cuvettes with a glass bead activator containing heparinase, and compared the Sonoclot data before and after cardiopulmonary bypass (CPB) to assess the usefulness in predicting postoperative hemorrhage. Methods In 41 cardiac surgery patients, Sonoclot data were obtained immediately after heparin administration (pre-bypass) and just before protamine administration (post-bypass). Excessive bleeding was defined as chest tube drainage greater than 2 ml·kg−1·h−1 in 1 h during the first 4 h after surgery. Results There were no significant differences in Sonoclot values before and after CPB in patients with acceptable bleeding (n = 29). In patients with excessive bleeding (n = 12), Sonoclot variables reflecting fibrin formation (activated clotting time [ACT], rate of fibrin formation [clot rate], and peak clot signal) were preserved after CPB; however, the variables reflecting platelet-fibrin interaction (time to peak, peak angle, and clot retraction rate) were significantly different from their respective pre-bypass values. Sonoclot analysis showed impairment of clot maturation after CPB in patients with excessive postoperative bleeding. Conclusion Our results suggest that abnormal postoperative hemorrhage can be predicted by Sonoclot analysis with a new glass bead-activated heparinase test performed after CPB.  相似文献   

14.
目的 应用sonoclot分析仪(SCT)观察止血环酸在心脏手术中的血液保护效果。方法36例心脏手术患者分成工组(抑肽酶,n=12)、Ⅱ组(止血环酸,n=12)和Ⅲ组(非用药组,n=12)。Ⅰ、Ⅱ组在心肺转流(CPB)下完成心脏手术,Ⅲ组则为非CPB下的冠脉搭桥手术。应用SCT观察切皮前和鱼精蛋白中和肝素后的凝血和血小板(Plt)功能的变化。结果 sonACT在T_1时点Ⅲ组为(123.21±18.58)s,明显高于Ⅰ组的(110.36±24.72)s和Ⅱ组的(106.09±13.91)s(P均<0.05);纤维蛋白凝集率(clot rate)、Plt功能在T_1与T_2时点三组之间均无显著差异。Plt在T_2时点Ⅲ组则明显高于Ⅰ、Ⅱ组。Ⅰ、Ⅱ组在T_2时点的Plt较T_1下降非常显著(P<0.01),Ⅲ组则无明显改变。结论 止血环酸对CPB下心脏手术患者凝血与Plt功能的影响与抑肽酶相似,非CPB下冠状动脉搭桥术对血液系统的影响明显减轻。  相似文献   

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16.
目的比较正常妊娠与自然流产小鼠模型蜕膜组织肿瘤坏死因子-α(TNF-α)及其受体1(TNFR1)和血清可溶性肿瘤坏死因子受体1(sTNFR1)的表达,探讨其与不明原因自然流产的关系。方法建立正常妊娠小鼠模型CBA×BALB/C和自然流产模型CBA×DBA/2。采用免疫组化SABC法测定两组模型孕13 d蜕膜组织TNF-α、TNFR1表达水平;酶联免疫吸附试验(ELISA)测定两组模型孕13 d血清sTNFR1表达水平。结果与正常妊娠模型相比,自然流产模型蜕膜组织中TNF-α、TNFR1表达显著升高(P<0.01);血清sTNFR1表达水平也高于正常妊娠模型(P<0.05)。结论TNF-α、TNFR1、sTNFR1可能与自然流产的发生发展有关。某些病理情况引发的蜕膜TNF-α、TNFR1表达增加也许是自然流产发生的原因之一,sTNFR1水平升高可能对妊娠具有自我保护和自我稳定的生理意义。  相似文献   

17.
目的 观察骨肉瘤患者肿瘤坏死因子 (TNF)基因多态性,探讨骨肉瘤与TNF基因多态性的相关性.方法 应用聚合酶链反应-限制性片段长度多态性分析方法(PCR-RFLP) 对52例骨肉瘤患者与60例健康对照者TNF-α和TNFβ基因的NcoI酶切位点进行对比分析.结果 52例骨肉瘤患者TNF-α- 308位点G/G基因型频率(98%) 及G等位基因频率(99%) 显著高于正常对照组G/G基因型频率85.0%及G等位基因频率91.7%(P<0.05),TNF-β+252的基因型频率和等位基因频率与正常对照人群比较差异无统计学意义(P>0.05). 结论 TNFα基因多态性与骨肉瘤的发生具有相关性,TNFβ基因多态性与骨肉瘤的发生无明显相关.  相似文献   

18.
目的 探讨右美托咪定对心肺转流(CPB)下行冠状动脉旁路移植术(CABG)患者心脏同步化运动的影响.方法 择期CPB下行CABG患者24例,年龄43~75岁,体表面积1.53~2.00m2,ASAⅡ或Ⅲ级,心功能Ⅱ或Ⅲ级.采用随机数字表法分为两组:右美托咪定组(D组)和对照组(C组),每组12例.两组术中麻醉维持均采用全凭静脉麻醉,D组于主动脉开放后经微量注射泵静注右美托咪定负荷剂量0.5μg/kg(10 min内注射完),然后以0.5 μg·kg-1·h-1维持给药至术毕,C组静注等量生理盐水.分别于开胸前(T1)和CPB停机后30 min(T2)、60 min(T3)记录血流动力学指标:HR、MAP、CVP、心脏指数(CI),左右心室收缩功能指标:左室射血分数(LVEF)、右室射血分数(RVEF)和心脏同步性参数:PR间期、QRS时限、室间机械延迟(IVMD).结果 与T1时比较,T2、T3时两组HR明显增快、CI明显升高(P<0.01);与C组比较,D组T2、T3时PR间期明显延长(P<0.05).两组间QRS时限及IVMD差异无统计学意义.结论 CPB下冠状动脉旁路移植术患者,右美托咪定负荷剂量0.5μg/kg后以0.5μg· kg-1·h-1维持能够延长PR间期,影响房室间同步化运动,但对左右心室间电机械同步化运动无明显影响.  相似文献   

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20.
参附注射液对肠缺血-再灌注大鼠肿瘤坏死因子α的影响   总被引:5,自引:0,他引:5  
目的观察肿瘤坏死因子α(TNF-α)在大鼠肠缺血-再灌注损伤过程中的作用及参附注射液对TNF-α的影响,探讨参附注射液防治肠缺血-再灌注损伤机制。方法 SD大鼠随机分为肠缺血-再灌注组(IR组)、参附注射液预处理组(SF组)和假手术组(C组)。采用阻断肠系膜上动脉(SMA)的方法制造肠缺血-再灌注模型。分别测定各组动物血浆、肠组织TNF-α含量及血液动力学变化;光镜观察肠粘膜损伤情况。结果IR组再灌注后MAP下降,与C组和SF组比有显著性差异(P<0.01);SF组肠粘膜损伤程度减轻,与IR组比有显著性差异(P<0.01);SF组血浆及肠组织TNF-α水平降低,与IR组比有显著性差异(P<0.01)。结论参附注射液可明显防治大鼠肠缺血-再灌注导致的肠粘膜损伤,这种作用可能是通过抑制TNF-α的释放实现的。  相似文献   

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