NBD多肽对大鼠急性坏死性胰腺炎的影响

(76±6.7)ng/L、(387±67)ng/L、8.71±0.45、(49.26±2.15)%;多肽预处理后血清TNF-α和IL-6水平、胰腺病理分值、NF-κB p65蛋白阳性表达率分别为(48±4.5)ng/L、(295±48)ng/L、6.76±0.26、(37.46±1.68)%,两组相差均非常显著(P＜0.05).结论 NBD多肽预处理可抑制ANP大鼠胰腺组织NF-κB的过度活化,下调炎症因子TNF-α、IL-6的表达,减轻胰腺损伤.     

核因子-κB在急性胰腺炎中的激活及NBD多肽的干预作用

目的:探讨核因子-κB(nuclear factor-kappaB.NF-KB),及活性氧簇(reactive oxygen species,ROS)在大鼠SAP发病过程中的作用:并观察NF-κB必需调节蛋白结合域(NF-κB essential modifier binding domain,NBD)多肽对大鼠SAP的干预作用.方法:逆行胰胆管内注射50 g/L牛磺胆酸钠(1mL/kg)制备大鼠SAP模型.大鼠64R,随机分成4组:假手术组,SAP组,TAT-NBD(WT)多肽组和TAT-NBD(MT)多肽组.术后6,12 h处死大鼠,观察胰腺组织病理、血清淀粉酶和胰腺组织NF-κB P65蛋白的变化.检测胰腺组织MDA含量及T-SOD活力.结果:与假手术组比较,SAP模型组6,12 h大鼠NF-κB P65蛋白表达显著升高(49.3±2.2vs 4.3±1.4,65.8±1.8 vs 5.0±1.3,均P<0.05);MDA生成增加(212.7±12.5 vs 87.7±7.5,296.8±13.3 vs 96.2±8.3,均P<0.05),T-SOD活力下降(88±10 vs 183±10,65±7 vs 194±10,均P<0.05);与SAP模型组比较,TAT-NBD(WT)多肽预处理6,12 h后,NF-κB P65蛋白表达(25.9±2.3,38.9±2.6)显著降低(P<0.05),MDA生成(102.5±10.4,164.5±12.2)降低(P<0.05);T-SOD活力(153±11,168±12)增加(P<0.05),胰腺病理学评分下降(5.04±0.41 vs 8.71±0.45,5.45±0.34 vs 10.31±1.23,均P<0.05),淀粉酶无明显变化.TAT-NBD(MT)多肽组上述指标均无明显变化.结论:SAP时大鼠胰腺组织的NF-κB过度激活,活性氧簇生成增加;NBD多肽预处理可以抑制NF-κB过度活化,减少活性氧簇生成,减轻胰腺局部炎症损伤.     

川芎嗪对人骨肉瘤MG-63细胞生长的抑制作用观察及机制探讨

目的 探讨川芎嗪对人骨肉瘤MG-63细胞生长的抑制作用及可能机制.方法 取对数生长期的人骨肉瘤MG-63细胞,随机分为川芎嗪低浓度组、高浓度组和对照组,川芎嗪低浓度组、高浓度组分别予3、30 mg/mL的川芎嗪,对照组加入完全培养液;48 h后采用四氮唑盐比色法检测MG-63细胞增殖抑制率;流式细胞术检测细胞凋亡率和细胞周期分布;Westemblot法检测Bcl-2、CyclinD1及NF-κB p65蛋白表达水平.结果 与对照组比较,川芎嗪低浓度组、高浓度组MG-63细胞增殖抑制率、凋亡率及G0/G1期细胞比例均明显升高,NF-κB p65及其靶基因Bcl-2、CyclinD1蛋白表达水平均明显降低,且川芎嗪高浓度组作用更明显;P均＜0.05.结论 川芎嗪对体外培养的MG-63细胞有增殖抑制作用,其机制可能与其促进MG-63细胞凋亡、诱导G0/G1期阻滞、抑制NF-κB及其靶基因的蛋白表达有关.     

控氧灌注对体外循环犬肺损伤的影响及机制探讨

目的探讨控氧灌注(OCR)对体外循环犬肺缺血再灌注损伤的影响及机制。方法将14只健康犬随机分为OCR及IR组各7只。两组均开胸建立体外循环,经过60 min升主动脉阻断和90 min再灌注。OCR组主动脉开放瞬间FiO2为40%,随后每5 min依次上调10%,最后达80%并保持至实验结束;IR组主动脉开放后再灌注全程FiO2保持80%不变。开胸后(T1)、主动脉开放后25 min(T2)、90 min(T3)分别留取血液标本及肺标本,检测血清IL-6和TNF-α含量,肺组织核转录因子κB(NF-κB)蛋白表达、髓过氧化物酶(MPO)活性、丙二醛(MDA)含量、肺组织干湿重;光镜下观察肺组织病理变化。结果 OCR组动脉血氧分压于主动脉开放后各时点均低于IR组(P<0.05);T2和T3时OCR组肺组织NF-κB蛋白表达显著低于IR组(P均<0.05),肺组织MPO活性、MDA,血IL-6和TNF-α水平明显低于IR组。OCR组肺组织干湿重比在T2和T3时点明显高于IR组,病理改变较轻。结论控氧灌注可减轻体外循环肺损伤;其机制可能为降低肺组织NF-κB蛋白表达及减轻局部炎症反应。     

核因子-κB活化机制及其对粥样斑块细胞的作用

核因子－κB是调节细胞基因转录的关键因子之一,它参与了许多与炎症反应有关的基因的表达调控。动脉粥样是硬化是一种炎症性疾病,核因子－κB存在于参与病变发展的多种细胞内,与病变的发生和发展有关,本文就核因子－κB的概况及在动脉粥样硬化病变发生和发展中的作用做一综述。     

金芪降糖片对糖尿病大鼠肾NF-κB p65表达的影响及机制

目的 探讨金芪降糖片对核转录因子-κB p65(NF-κB p65)表达的影响及机制.方法 将大鼠适应性喂养2周后随机留取30只作为正常对照组(N组),尾静脉注射枸橼酸缓冲液,其余尾静脉注射60 mg/kg的STZ制作糖尿病模型,将造模成功的大鼠以血糖为标准分为糖尿病组(DM组)和给药组(DD组).DD组按4.2 g/(kg·d)给予金芪降糖片生粉灌胃,DM组和N组予等量生理盐水灌胃,共喂养20周,检测平均血糖值(APG)、24 h微量白蛋白(UMA)、内生肌酐清除率(Ccr)、肾脏形态学检查、NF-κB p65表达水平.结果 4、12、20周时DD组和DM组APG均明显高于N组,4、12周时DD组和DM组UMA均明显高于N组,20周时DM组UMA、NF-κB p65明显高于、Ccr明显低于N组和DD组,P均＜0.05;光镜和电镜均发现DD组的病理改变明显轻于DM组.结论 金芪降糖片能有效降低糖尿病肾组织中NF-κB p65水平并减轻糖尿病慢性肾损伤的程度,其机制可能与其降脂、抗氧化及降低NF-κB p65水平,抑制肾组织微炎症反应有关.     

小鼠脏器核转录因子NF-κB活性观察

目的　为了研究核转录因子 (NF κB)在老化小鼠各脏器中的表达及其活性的改变 ,以期探讨其在老化及多器官功能不全发生过程中的作用。方法　用免疫组化法检测NF κB在小鼠各脏器中的表达情况 ,同时用凝胶阻滞分析法观察NF κB的活性。结果　在老化小鼠的各脏器中 ,NF κB的表达量及活性均有不同程度的增加 ,尤以肺脏的改变最为显著。结论　NF κB可能是老化及肺启动的老年多器官功能不全过程中的一个非常关键的转录因子。     

小鼠脏器核转录因子NF-кB活性观察

目的为了研究核转录因子(NF-кB)在老化小鼠各脏器中的表达及其活性的改变,以期探讨其在老化及多器官功能不全发生过程中的作用.方法用免疫组化法检测NF-κB在小鼠各脏器中的表达情况,同时用凝胶阻滞分析法观察NF-κB的活性.结果在老化小鼠的各脏器中,NF-κB的表达量及活性均有不同程度的增加,尤以肺脏的改变最为显著.结论NF-κB可能是老化及肺启动的老年多器官功能不全过程中的一个非常关键的转录因子.     

核转录因子-κB抑制因子对中性粒细胞凋亡的影响

目的 探讨脂多糖(LPS)刺激下核转录因子-κB(NF-κB)抑制因子(IκBα)对中性粒细胞凋亡的影响.方法 离体培养人中性粒细胞,分为生理盐水对照组(A组)、来普霉素B(LMB)干预组(B组)、LPS刺激组(C组)和LMB +LPS组(D组).各组分别在刺激后120 min ,用 Western印迹检测细胞核、胞浆中IκBα含量,用NF-κBp65试剂盒检测细胞核NF-κB活性,流式细胞仪检测中性粒细胞凋亡百分比.结果 C组胞浆及胞核中IκBα含量较A组中明显减少,而NF-κB活性显著增加,中性粒细胞凋亡比例减少;D组胞核中IκBα含量较C组中明显增多, NF-κB活性明显抑制,中性粒细胞凋亡比例增加.结论 IκBα的核内聚集可抑制NF-κB活性,并促进炎症状态下中性粒细胞凋亡.     

利多卡因对大潮气量机械通气所致大鼠肺损伤及NF-κB基因表达的影响

目的观察利多卡因对大潮气量机械通气所致大鼠肺损伤和核转录因子-κB(NF-κB)基因表达的影响.方法将36只清洁级成年雄性SD大鼠随机分为R组、N组、L组各12只,三组均腹腔注射20%乌拉坦0.8ml/kg麻醉,用14号B-D留置针行气管插管,各项操作完毕后稳定30 min,取三组各6只大鼠静脉注射伊万斯蓝(EB)50 mg/kg.R组自然呼吸,静滴林格液10 ml/(kg·h);N组和L组接小动物呼吸机,N组静滴林格液10 ml/(kg·h)、L组静脉注射2%利多卡因3 mg/kg[继之以3 mg/(kg·h)静滴维持至实验结束]后行大潮气量(Vt,40 ml/kg)机械通气,三组均呼吸空气,实验持续3 h放血处死.观察各组肺组织形态学变化及NF-κBmRNA表达.结果R组肺组织未见明显病理学变化,N组见肺间质和肺泡水肿、炎性细胞浸润、肺泡间隔断裂、偶见肺泡出血,L组变化介于上两者之间;与R组比较,N组、L组NF-κBmRNA/ACTIN mRNA条带灰度值均上调(P分别＜0.01,＞0.05);与R组比较,N组和L组NF-κB吸光度(△NF-κB)表达均上调(P分别＜0.05、＞0.05).结论大潮气量机械通气可导致大鼠肺部通透性增加并发生炎性改变,使NF-κB表达上调;利多卡因能抑制这种炎性改变及NF-κB表达上调,此可能是其抑制肺炎性反应的机制之一.     

Influence of polyunsaturated fatty acids on survival of skin allografts and tumor incidence in mice.

Subcutaneous or oral administration of the polyunsaturated fatty acid linoleic acid prolongs survival of skin allografts in mice. Mice fed on a diet deficient in polyunsaturated fatty acids show a relative immunopotentiation, as indicated by accelerated skin allograft rejection and decreased incidence and rate of development of methylcholanthrene-induced tumors. These observations support the hypothesis that polyunsaturated fatty acids take part in immunoregulatory mechanisms.     

睡眠剥夺对大鼠心脏的影响及其致心律失常机制研究

目的：以Sprague-Dawley大鼠为研究对象，观察经过1d、3d、5d及7d睡眠剥夺（SleepDeprivation，SD）大鼠心电图及其心室肌组织Kv2．1钾离子通道水平，探索SD致心律失常的发生机制。方法：以改良多平台睡眠剥夺法（MMPM）建立睡眠剥夺模型，设笼养对照组，大平台对照组，睡眠剥夺1d、3d、5d、7d组，实时PCR定量监测各组大鼠心肌组织Kv2．1钾离子通道基因mRNA水平随SD时间变化趋势。结果：SD后大鼠心电图改变以心律失常为主，心肌组织Kv2．1钾离子通道的水平随SD时间的延长持续下调（笼养对照组，大平台对照组，睡眠剥夺1d，3d，5d．7d组的2^-△△ct值依次为1，0．84，0．60，0．35，0．1，0．06，各睡眠剥夺组的较两对照组显著下降（P〈0．05）。结论：SD可致大鼠发生心律失常，心肌组织Kv2．1钾离子通道水平的下调可能是SD致心律失常的机制之一。     

单硝酸异山梨酯对慢性心力衰竭小鼠心功能的影响及作用机理

目的探讨单硝酸异山梨酯(ISMN)对慢性心衰(CHF)小鼠心功能的影响及其可能的作用机理。方法100只C57BL/6J品系雄性小鼠随机分为假手术组、模型组、ISMN低剂量组、中剂量组和高剂量组。构建CHF小鼠模型后,ISMN低剂量组、中剂量组和高剂量组小鼠每天分别给予50 mg、200 mg、400 mg的ISMN灌胃,假手术组和模型组小鼠给予等体积的生理盐水灌胃,持续给药6周。采用多普勒超声心电图检测各组小鼠心功能指标LVESD、LVEDD、LVEF、LVFS的变化;采用HE染色检查小鼠心肌组织病理学改变;采用全自动血液流变测试仪检测小鼠全血高切粘度、全血低切粘度、血浆粘度和红细胞聚集指数;采用NOS、SOD、MDA和GSH-Px检测试剂盒测定小鼠血清NOS、SOD、MDA和GSHPx水平。结果模型组小鼠LVESD和LVEDD较假手术组显著升高,LVEF和LVFS则显著降低;与模型组比较,ISMN各剂量组小鼠LVESD和LVEDD呈剂量依赖性下降,LVEF和LVFS呈剂量依赖性上调,差异有统计学意义(P<0.05);HE染色显示,与假手术组比较,模型组小鼠心肌细胞肥大且呈局灶性坏死,肌纤维间隙增加,并伴有大量炎性细胞浸润;与模型组比较,ISMN各剂量组小鼠心肌细胞肥大和坏死程度依次降低,肌纤维排列趋向规整,炎性浸润程度明显降低,且呈显著的剂量依赖性,差异有统计学意义(P<0.05);模型组小鼠全血高切粘度、全血低切粘度、血浆粘度、红细胞聚集指数、MDA血清含量较假手术组显著升高,SOD、GSH-Px和NOS的血清含量则显著下降;与模型组比较,ISMN各剂量组小鼠全血高切粘度、全血低切粘度、血浆粘度、红细胞聚集指数、MDA血清含量均呈剂量依赖性下降,SOD、GSH-Px和NOS血清含量则呈剂量依赖性升高,差异均有统计学意义(P<0.05)。结论ISMN可通过抑制细胞氧化应激和炎性反应水平,改善CHF小鼠微循环障碍和心功能损伤,值得临床中大力推广。     

The impact of diabetes mellitus at the time of heart transplantation on long-term survival

AIMS/HYPOTHESIS: To analyse the impact of diabetes mellitus (DM) at the time of heart transplantation on long-term survival and incidence of transplant coronary artery disease (TxCAD). METHODS: We analysed 773 consecutive adult heart transplant recipients who underwent primary heart transplantation from May 1986 until December 2000. The cohort consisted of 140 patients with diabetes mellitus (with DM, men 82%) and 633 patients without (wo DM, men 84%) diabetes mellitus at the time of transplantation. The patients were documented as to survival and incidence of TxCAD. RESULTS: Patients with diabetes mellitus were older compared to those without diabetes mellitus (with DM 54.9+/-6.8a vs wo DM 49.7+/-10.8a; p=0.0001), they had a higher incidence of ischaemic cardiomyopathy prior to transplantation (with DM 52% vs wo DM 30%; p=0.0001), but reduced long-term survival (10 year survival: with DM 40% vs wo DM 58%; log-rank=0.025). Surprisingly, the incidence of transplant coronary artery disease (TxCAD) was comparable at 10 years (with DM 28% vs wo DM 22%; log-rank=0.625). In multivariate Cox proportional hazard analysis, diabetes mellitus present at the time of heart transplantation (HR 1.594; 95%CI 1.009-2.518; p=0.045), but not age (HR 0.990; 95%CI 0.965-1.014; p=0.404) was an independent predictor affecting long-term survival. CONCLUSION/INTERPRETATION: The presence of diabetes mellitus at the time of heart transplantation adversely affects long-term patient survival, but does not predict the occurrence of transplant coronary artery disease. The definite mechanisms of adverse survival primarily seem to relate to generally impaired global organ function. Despite a less favourable long-term outcome, our data still justify heart transplantation in end-stage heart failure patients with diabetes mellitus.     

Effects of social isolation stress on immune response and survival time of mouse with liver cancer

AIM: To investigate the effects of isolation stress on mouse with liver cancer and possible associated mechanisms. METHODS: Transplantable murine hepatoma22 (H22) model was used to evaluate the effects of social isolation stress on murine liver cancer. Mice were immunized with sheep red blood cell (SRBC) and intraperitoneally inoculated with H22 cell, then divided into two groups, one reared individually as group (I) and the other reared in groups as group (G). Titer of antibody to SRBC and interleukin 2 (IL-2) in serum was monitored. The survival time of mouse with liver cancer was observed. RESULTS: The titer of antibody to SRBC in group (G) was 1:24.5 and that in group (I) was 1:11.2. There was a significant difference between these two groups (t=2.60, P=0.02). A significant difference in IL-2 concentration was observed between group (G) (39.6 ng/L) and group (I) (47.1 ng/L, t=2.14, P=0.046). The survival time in group (G) (16.5 d) was markedly longer than that in group (I) (13.2 d, t=3.46, P=0.002). CONCLUSION: Our study suggests that survival time of the mouse bearing H22 tumor is affected by the social isolation stress and the associated mechanism may be the immunological changes under the social isolation stress.     

Early detection of rejection and assessment of cyclosporine therapy by 111In antimyosin imaging in mouse heart allografts

BACKGROUND. Mice (n = 58) with abdominal heterotopic heart transplants were studied to examine the effectiveness of 111In-labeled antimyosin scintigraphy in the detection of rejection and to determine the consequence of cyclosporine therapy on the results. METHODS AND RESULTS. Allografts from B10D2 donors were transplanted into B6AF1 recipients. Of the 49 allografted mice, 19 were treated with cyclosporine (15 mg/kg.day). Nine isografted mice served as controls. Scintigraphy was performed by injecting 100 muCi 111In antimyosin monoclonal antibody 2-15 days after transplantation. An increase in the ratio of percent dose of antimyosin injected per gram (% dose/g) of the grafted heart (G) to that of the autologous heart (A) (G/A) as well as the increasing percent dose per gram of antimyosin in the grafts reflected the severity of histopathological rejection regardless of the presence or absence of cyclosporine. Scintigraphic images demonstrated unequivocally intense accumulation of 111In in rejected allografts as confirmed by histologically demonstrable myocyte necrosis. The G/A ratio in allografted mice with mildly deteriorated mechanical activity (4.2 +/- 1.0, mean +/- SD) was greater than that in mice with normal contractility (1.8 +/- 0.7) (p less than 0.001), and the necrosis correlated with this modest decline in mechanical function could be scintigraphically identified. Of mice with normally contracting allografts, the G/A ratio was greater in animals with demonstrated myocyte necrosis (2.6 +/- 0.5) than in those without necrosis (1.5 +/- 0.5) (p less than 0.001). In contrast, isografted mice or a subset of allografted mice treated with cyclosporine and not showing evidence of rejection did not manifest any significant change in G/A ratio, nor did they have scintigrams positive for rejection as late as 15 days after transplantation. CONCLUSIONS. These findings suggest that antimyosin scintigraphy is a sensitive and early indicator of cardiac transplant rejection and that it could be useful as a noninvasive method for assessing the efficacy of cyclosporine treatment.