Activation of NF-κB and its regulation on IL-6 expression during LPS-induced liver injury

Objective： To explore the kinetics of the activation of nuclear factor-kappa B （NF-κB） and its regulation of interleukin-6 （IL-6） expression during LPS induced liver injury. Methods： Kunming mice were randomly divided into 4 groups in order to observe the does effect relationship at 3h： normal saline solution （control） group, low （1 mg/kg）, middle （5 mg/kg）, and high （10 mg/kg） LPS-induced groups; 6 groups in order to observe the time-effect relationship of 5 mg/kg LPS injection： normal saline solution （control） group, 0.5, 1, 3, 5 and 8 h groups ; pyrrolidine dithiocarbamate （PDTC） intervened groups （3 h）： normal saline solution （control） group, 5 mg/kg LPS, 200 mg/kg PDTC, and 200 mg/kg PDTC＋5 mg/kg LPS groups. NF-κB activities of Kupffer cells were determined with electrophoretic mobility shift assay （EMSA） and expression levels of IL-6 were measured with enzyme-linked immunosorbent assay （ELISA）. Results： Does-effect of NF-κB activities in Kupffer cells after LPS injection 3 h： NF-κB activation could be detected in 1 mg/kg LPS group, reached the highest level in 5 mg/kg LPS group, and persisted in 10 mg/kg LPS group; time-course after 5 mg/kg LPS injection： the DNA-binding activity was observable at 0.5 h after LPS injection, increased significantly at 3 h, and persisted for at least 8 h; in addition, antioxidant PDTC could inhibit the activation of NF-κB significantly. The kinetics of IL-6 level in liver tissues during LPS-induced liver injury were that IL-6 level after 3 h of injection increased first and then reduced; the same trend was observed in the time-course on IL-6 level after LPS injection; PDTC could significantly inhibit the release of IL-6. Correlation analyses revealed that IL-6 level was significantly and positively correlated with the activation of NF-κB. Conclusion ： NF-κB in Kupffer cells can be activitied during LPS-induced liver injury to some extent, and NF-κB may have some regulation on the expression of IL-6.     

肾毒血清肾炎大鼠肾组织中NF-κB活化及其意义

目的：探讨肾毒血清性肾炎大鼠肾组织核因子—κB(NF—κB)活化及其意义。方法：肾毒血清肾炎应用兔抗鼠肾小球基膜肾毒血清制备。应用凝胶电泳迁移率(EMSA)和Western blot检测。肾毒血清。肾炎大鼠。肾组织中NF-κB活化及IκBα和IκBβ的降解；采用核酸酶保护法检测肾组织中IL-8表达，并分析其与NF—κB活化的关系。结果：模型组肾组织中IL-8表达显著高于正常对照组；肾毒血清肾炎大鼠肾组织中NF—κB活化显著增强，p65由胞质转移至咆核．咆质内IκBα和IκBβ降解明显增加；NF-κB活化与IL-8表达呈显著正相关。结论：NF—κB／IκB信号通路介导小球肾炎肾组织中IL-8表达。     

Dexamethasone impairs the differentiation and maturation of murine dendritic cells by Toll-like receptor 4-nuclear factor-κB pathway

Background Recent studies have demonstrated that dexamethasone （DEX） interferes with immune responses by targeting key functions of dendritic cells （DCs） at the earliest stage. However, the cellular and molecular mechanisms are still incompletely understood. This study aimed to explore the possible mechanisms by investigating the roles of DEX on differentiation, maturation ＆ function of murine DCs and the effects of DEX on DCs via Toll-like receptor 4 （TLR4）-nuclear factor （NF）-KB mediated signal pathway. Methods Immature DCs （imDCs） were cultured from murine bone marrow （BM） cells. We added DEX into culture medium at different time. The expression of CD11c, CD86 and I-Ab （mouse MHC class II molecule） was determined by flow cytometry. We determined the expression of NF-κB and its inhibitory protein I-κBα by electrophoretic mobility shift assay （EMSA） and Western blotting, respectively. The productions of interleukin （IL）-12p70 and IL-10 in cell culture supernatants were determined by enzyme-linked immunosorbent assay （ELISA）. Results DEX impaired differentiation of DCs from murine bone marrow progenitors, and inhibited lipopolysaccharide （LPS） induced maturation of DCs. DEX significantly inhibited NF-κB expression of normal DCs, the higher the DEX concentration or the longer the DEX treatment time, the more obvious the effect. However, DEX had little effect on LPS-induced NF-KB activation, and partially impaired LPS-induced I-κBα degradation. DEX significantly decreased LPS induced IL-12p70 production by DCs. Interestingly, our results showed a synergistic effect between DEX and LPS on the production of IL-10 by DCs. Conclusions DEX inhibits the differentiation and maturation of murine DCs involved in TLR4-I-κB-NF-κB pathway, and also indirectly impairs Thl development and interferes with the Thl-Th2 balance through IL-12 and/or IL-10 secretion by DCs.     

China introduce new bird flu measures ahead of spring period

Background Restoration of blood flow to the ischemic liver lobes may paradoxically exacerbate tissue injury, which is called hepatic ischemia/reperfusion injury （IRI）. Toll-like receptor 4 （TLR4）, expressed on several liver cell types, and the nuclear factor-kappa B （NF-KB） signaling pathway are crucial to mediating hepatic inflammatory response. Because IRI is essentially a kind of profound acute inflammatory reaction evoked by many kinds of danger signals, we investigated TLR4/NF-KB signaling pathway activation in a murine model of partial hepatic IRI. Methods Wild-type mice （WT, C3H/HeN） or TLR4 mutant mice （C3H/HeJ） were subjected to 45 minutes of partial hepatic ischemia followed by 1 hour, 3 hours of reperfusion. Sham group accepted the same procedure without the obstruction of blood supply. At the end of reperfusion, the compromise of liver function and the histological change of liver sections were measured as the severity of liver injury. The level of endotoxin in the portal vein was measured by limulus assay. NF-KB activation was determined by electrophoretic mobility shift assay （EMSA）. The levels of tumor necrosis factor-a （TNF-a） and intedeukin-1β （IL-1β） in systemic blood after hepatic IRI were assessed by enzyme-linked immunosorbent assay （ELISA）. Results The compromise of liver function and the morphological injuries in mutant mice were relieved more markedly than those in WT mice after partial hepatic IRI. NF-KB activation in WT mice was stronger than that in TLR4 mutant mice, and both were stronger than those in the sham operated mice （P〈0.01）. Endotoxin in each group was undetectable. The levels of TNF-α and IL-1β in systemic blood were elevated in both strains, but lower in the sham operated group. These mediators were significantly decreased in TLR4 mutant mice compared with those in WT mice （P〈0.01）. Conclusions The TLR4/NF-KB signaling pathway may mediate hepatic IRI triggered by endogenous danger signals. Inhibition of the TLR4/NF-KB pathway may be a potential therapeutic target for attenuating ischemia/reperfusion-induced tissue damage in some clinical settings.     

NMBR在不同妊娠阶段小鼠子宫平滑肌细胞中的表达及其与临产的关系

目的：探讨神经调节素B受体（neuromedin B receptor,NMBR）在妊娠小鼠子宫平滑肌细胞中mRNA、蛋白时空表达的变化及其与分娩启动的关系和机制。方法：按妊娠阶段的不同,将小鼠分为未孕组、早孕组、中孕组、晚孕组、产时组和产后组,每组12例。应用半定量RT-PCR和Western免疫印迹技术分别检测子宫平滑肌中NMBR, IL-6和HSP70 mRNA及蛋白表达;利用NoShift转录因子分析法检测NF-κB-P65的DNA结合活性, 并分析各指标与分娩的关系及其相关性。结果：产时组NMBR mRNA的相对表达量显著高于未孕、早孕、晚孕、产后组（P＜0.05）, 但与中孕组相比差异无统计学意义（P＞0.05）;产时组NMBR蛋白表达量显著高于其它各组（P＜0.01）。NF-κB-P65DNA结合活性产时组显著高于未孕、晚孕和产后组（P＜0.05）。IL-6 mRNA表达产时组显著高于未孕、晚孕和产后组（P＜0.05）, 其蛋白表达产时组亦显著高于未孕和产后组（P＜0.05）。HSP70 mRNA表达量产时组显著高于未孕和产后组（P＜0.05）,HSP70蛋白的表达量产时组明显高于晚孕、未孕组（P＜0.05）。临产前后子宫平滑肌细胞P65 DNA结合活性、IL-6 mRNA的表达均与NMBR mRNA的变化呈正相关（r=0.40, P＜0.01;r=0.30, P＜0.05）; P65, HSP70 mRNA的变化亦与NMBR的变化呈正相关（r=0.40, P＜0.01;r=0.49, P＜0.01）;但HSP70与P65无相关性。结论：子宫平滑肌细胞中NMBR mRNA和蛋白表达在临产时达最高峰。NMBR可借助NF-κB P65-IL-6通路、通过调节HSP70表达参与分娩发动和维持,但其对HSP70表达的影响不依赖P65途径。     

NF-κB信号转导通路与胰岛素抵抗

核因子-κB（NF—κB）信号转导通路包括NF—κB、NF—κB抑制蛋白（IκB）和IκB激酶（IKK）。其中,NF—κB是一种重要的核转录因子,参与炎症反应、免疫反应、细胞凋亡及物质代谢等多种生物进程。IKK具有丝氨酸／苏氨酸激酶活性,能使多种蛋白的丝氨酸／苏氨酸残基磷酸化。NF—κB信号转导通路的活化与胰岛素抵抗的发生密切相关。文章就NF—κB在胰岛素抵抗发生中作用作一综述。     

大鼠脑出血后脑肺组织NF-κB的表达及其在急性肺损伤中的作用

目的 探讨NF-κB在脑出血(intracerebral hemorrhage,ICH)后在脑、肺组织的表达及在急性肺损伤(acute lung injury ,ALI)中的作用.方法 采用自体血尾状核注入法制备脑出血大鼠模型.将35只大鼠随机分为假手术组(5只),脑出血组(30只),脑出血组又分为6 、12、 24 、48 h和3、5 d 6个亚组.应用HE染色观察各组脑出血周围组织与肺组织的炎症反应情况.RT-PCR法检测脑和肺组织中NF-κB p65 mRNA的表达.放射免疫法测定血清中TNF-α和IL-1β的含量.结果 脑出血后12 h脑水肿明显,24 h血肿周围炎症细胞浸润增多,48 h左右炎症反应最重;脑出血6 h即有间质性肺炎表现和局灶性肺气肿,48～72 h炎症反应达高峰,肺泡结构破坏明显;与假手术组相比,NF-κB p65 mRNA于脑出血6 h在脑血肿周围组织与肺组织中表达均开始增高(P＜0.01),48 h均达高峰(P＜0.01),3～5 d表达仍高于假手术组(P＜0.01);血清TNF-α含量在脑出血6 h开始增高(P＜0.01),48 h最高(P＜0.01),5 d时仍高于假手术组(P＜0.01);IL-1β在脑出血各组中含量均无增高.结论 脑出血可以通过引发炎症反应导致急性肺损伤,NF-кB在其病理生理学过程中起重要作用.     

脂多糖刺激N9小胶质细胞释放炎性因子的时间和剂量效应

目的研究脂多糖刺激N9小胶质细胞释放炎性因子的时间和剂量效应。方法不同剂量脂多糖刺激N9小胶质细胞,在不同时间点,酶联免疫吸附试验检测培养基中白细胞介素1β(IL-1β)和肿瘤坏死因子α(TNF-α)水平,硝酸还原酶法检测培养基中一氧化氮(NO)水平,Western blot检测细胞质和细胞核中核转录因子-κB(NF-κB)蛋白水平。结果刺激6、12 h后,各脂多糖组培养基中IL-1β和NO水平与对照组比较差异无统计学意义(P>0.05),刺激24 h后1 000、10 000μg.L-1脂多糖组培养基中的IL-1β和NO水平均较对照组升高(P<0.01)。刺激30 min后,各脂多糖组培养基中TNF-α水平与对照组比较差异无统计学意义(P>0.05),刺激6、24 h后,各脂多糖组培养基中TNF-α水平均较对照组升高,差异有统计学意义(P<0.01),且1 000μg.L-1脂多糖组TNF-α水平最高。Westernblot检测结果显示,各脂多糖组细胞质和细胞核内NF-κB蛋白水平较对照组显著增多(P<0.01),其中1 000μg.L-1脂多糖组细胞质和细胞核中NF-κB蛋白水平最高。结论 1 000μg.L-1脂多糖是激活N9小胶质细胞诱发其炎症反应的最佳剂量,脂多糖作用6 h主要促进TNF-α的释放,作用24 h后则IL-1β和NO的释放明显增加。     

热毒宁注射液对脂多糖诱导急性肺损伤大鼠的抗感染作用

Objective： To evaluate the protective effects of Reduning Injection （热毒宁注射液, RDN）, a patent Chinese medicine, on lipopolysaccharide （LPS）-induced acute lung injury （ALl） in rats and its underlying mechanisms of action. Methods： Sixty male Sprague-Dawley rats were randomly divided into 6 groups, including normal control, model, dexamethasone （DEX, 5 mg/kg）, RDN-H （720 mg/kg）, RDN-M （360 mg/kg） and RDN-L （180 mg/kg） groups, with 10 rats in each group. Rats were challenged with intravenous injection of LPS 1 h after intraperitoneal treatment with RDN or DEX. At 6 h after LPS challenge, lung tissues and bronchoalveolar lavage fluid （BALF） were collected, and the number of inflammatory cells was determined. The right lungs were collected for histopathologic examination, measurement of gene and protein expressions, superoxide dismutase （SOD） and myeloperoxidase （MPO） activities. Results： In vivo pretreatment of RDN （360, 720 mg/kg） significantly reduced the weight of wet to dry （W/D） ratio of lung, protein content in BALF, and led to remarkable attenuation of LPS-induced histopathological changes in the lungs. Meanwhile, RDN enormously decreased BALF total inflammatory cells, especially neutrophil and macrophage cell numbers. Moreover, RDN increased SOD activity, inhibited MPO activity, alleviated LPS-induced tumor neurosis factor-o~ （TNF-o~） and inducible nitric oxide synthase （iNOS） expression in lung tissues. Furthermore, RDN （720 mg/kg） efficiently weakened nuclear factor- kappa B （NF- K B） gene and protein expression. Conclusion： Anti-inflammatory effects of RDN was demonstrated to be preventing pulmonary neutrophil infiltration, lowering MPO activity, TNF-oL and iNOS gene expression by inhibiting NF- K B activity in LPS-induced ALl.     

Anti-Inflammatory Effects of Redlining Injection (热毒宁注射液)on Lipopolysaccharide-lnduced Acute Lung Injury of Rats

Objective:To evaluate the protective effects of Reduning Injection(热毒宁注射液.RON),a patent Chinese medicine,on lipopolysaccharide(LPS)-induced acute lung injury(ALI)in rats and its underlying mechanisms of action.Methods:Sixty male Sprague-Dawley rats were randomly divided into 6 groups,including normal control,model,dexamethasone(DEX,5 mg/kg),RDN-H(720 mg/kg),RDN-M(360 mg/kg)and RDN-L(180 mg/kg)groups,with 10 rats in each group.Rats were challenged with intravenous injection of LPS 1 h after intraperitoneal treatment with RDN or DEX.At 6 h after LPS challenge,lung tissues and bronchoaiveolar lavage fluid(BALF)were collected,and the number of inflammatory cells was determined.The right lungs were collected for histopathologic examination,measurement of gene and protein expressions,superoxide dismutase(SOD)and myeloperoxidase(MPO)activities.Results:In vivo pretreatment of RDN(360,720 mg/kg)significantly reduced the weight of wet to dry(W/D)ratio of lung,protein content in BALF,and led to remarkable attenuation of LPS-induced histopathological changes in the lungs.Meanwhile,RDN enormously decreased BALF total inflammatory cells,especially neutrophil and macrophage cell numbers.Moreover,RDN increased SOD activity,inhibited MPO activity,alleviated LPS-induced tumor neurosis factor-α(TNF-α)and inducible nitric oxide synthase(iNOS)expression in lung tissues.Furthermore,RDN(720 mg/kg)efficiently weakened nuclear factorkappa B(NF-κB)gene and protein expression.Conclusion:Anti-inflammatory effects of RDN was demonstrated to be preventing pulmonary neutrophil infiltration,lowering MPO activity,TNF-αand iNOS gene expression by inhibiting NF-κB activity in LPS-induced ALI.     

PDTC对重度颅脑损伤后NF-κB表达的影响

目的：观察核转录因子-κB（NF-κB）在大鼠创伤性脑损伤（TBI）后脑组织损伤区的表达变化，同时探讨吡咯烷二硫代氨基甲酸酯（PDTC）对其表达的影响。方法：参照改良Feeney自由落体脑损伤装置制备大鼠重度脑损伤模型，将72只大鼠随机分为TBI组、PDTC干预组和假手术对照组，每组分别于伤后2h、12h、24h、48h断头，取出损伤区脑组织，检测各组的NF-κBmRNA表达水平。结果：TBI组NF-κB于伤后2h表达增强，12h表达明显增加，24h达到高峰，48h略有下降，与假手术对照组相比差异显著（P〈0．05）。PDTC干预组与TBI组相比，NF—κBmRNA表达明显下降，差异显著（P〈0．05）。结论：大鼠重度TBI后，NF—κB的活化及过度表达参与了继发性脑损伤过程，PDTC可以通过抑制NF—κB的表达，对TBI起到保护作用。     

大鼠坐骨神经损伤后脊髓运动神经元凋亡及其机制研究

目的探讨大鼠坐骨神经损伤后雪旺细胞（schwann cells，SCs）中核因子-κB（nuclear factor-kappa B,NF-κB）的表达及其对脊髓运动神经元凋亡的调控作用。方法健康成年雄性SD大鼠36只，体重200～250g，随机分为正常对照组（n=-6）和坐骨神经钳夹损伤组（n=30）。采用免疫组化、计算机图像分析技术，对正常和损伤后不同时间1、3、7、14及21d的坐骨神经SCs中NF—κB的表达进行检测。同时取与坐骨神经相连的L4～L6段脊髓作原位末端标记技术（TUNEL）检测脊髓运动神经元的凋亡。结果与正常对照组相比较，损伤组坐骨神经SCs中NF—κB的表达显著改变，其变化趋势为先升高后降低，伤后3d达高峰。随后逐渐下降，21d接近正常值；损伤组脊髓运动神经元凋亡数在损伤后表现出相同的变化趋势。相关分析表明两者呈显著正相关。结论坐骨神经损伤后脊髓运动神经元发生不同程度的凋亡，SCs中NF—κB可能参与这种凋亡的调控过程。     

NF-κB反义寡核苷酸对博莱霉素致小鼠急性肺损伤的保护作用

目的研究转录因子NF-κB在博莱霉素(BLM)致小鼠急性肺损伤病理过程中的重要作用,及其反义寡核苷酸对肺损伤的防治作用。方法小鼠随机分为5组,于0d经小鼠尾静脉分别注射150mg/kg或300mg/kgBLM,在注射前6h和注射后第5d,150组和300组分别注射生理盐水(NS);anti150组和anti300组分别注射p65的硫甙反义寡核苷酸(900μg/只);同时设立正常对照组,分别在3个时间点(注射前6h、0d、第5d),经尾静脉注射NS,观察各组小鼠体质量变化、死亡情况和肺组织病理改变。结果(1)150组和anti150组死亡率分别为53%和0%(P<0.05);而300组和anti300组死亡率分别为100%和60%(P<0.05)。p65反义寡核苷酸抑制了BLM所致小鼠死亡;(2)150组和anti150组小鼠的最低体质量分别减轻至原来的(65.5±7.8)%和(82.1±3.4)%(P<0.01)。p65反义寡核苷酸改善了BLM所致小鼠体质量减轻;(3)肺组织HE染色显示,BLM致死的150组小鼠,可见肺组织血管结构丧失,出血性水肿,肺泡腔内大量炎性渗出;非BLM致死小鼠注射BLM后14d,可见肺组织大片实变,肺泡结构丧失。而anti150组14d明显减轻了BLM导致的肺组织损伤。结论NF-κB可能在BLM致小鼠急性肺损伤过程中具有重要作用。NF-κB反义寡核苷酸对BLM所致小鼠急性肺损伤具有保护作用。     

呼吸机所致肺损伤肿瘤坏死因子-α的表达及核因子-κB活性的实验研究

目的 研究呼吸机所致肺损伤(VILI)时肿瘤坏死因子-α(TNF-α)的表达及核因子-κB(NF-κB)DNA结合活性的变化,探讨VILI炎症反应的分子生物学机制.方法 应用大潮气量(VT)机械通气建立兔VILI模型.40只雄性新西兰兔随机分为对照组、常规VT组、损伤1 h组、2 h组及4 h组.用酶联免疫吸附法(ELISA)检测肺组织匀浆TNF-α含量,反转录多聚酶链反应(RT-PCR)检测mRNA表达.凝胶电泳迁移率分析法(EMSA)测定NF-κB的活性.同时检测动脉血氧分压(PaO₂)和肺湿质量/干质量比值(W/D)及肺组织病理学检查.结果 1) 损伤4 h组PaO₂较常规VT组显著降低(P<0.05),损伤4 h组W/D较对照组和常规VT组显著升高(P均<0.01).2) 损伤2 h组和损伤4 h组肺组织匀浆中TNF-α含量均显著高于对照组和常规VT组(P均<0.01).各损伤组TNF-α mRNA含量均显著高于对照组和常规VT组(P均<0.01),损伤4 h组高于损伤1 h组(P<0.01)和损伤2 h组(P<0.05).3) 各损伤组NF-κB的DNA结合活性均显著高于对照组和常规VT组(P均<0.01),2 h活性达峰值,4 h仍维持在高水平.结论 TNF-α升高参与了VILI的炎症反应过程,其升高可能与其mRNA表达增高有关.NF-κB的DNA结合活性增高可能参与了VILI时TNF-α的基因转录过程.     

超早期高压氧对急性脑外伤大鼠的疗效

目的：研究高压氧治疗大鼠创伤性脑损伤的疗效及其保护机制.方法：健康成年雄性SD大鼠24只,随机分为对照组和高压氧治疗组.采用Feeney法制造局灶性脑创伤模型,在相应的时间点处死大鼠,观察脑组织含水量及脑组织核转录因子κB（NF-κB）表达的变化.结果：高压氧治疗后,对照组的脑组织含水量显著高于治疗组,对照组的NF-κB的表达显著高于治疗组.结论：高压氧单次9h超早期治疗能减轻脑水肿,有显著的脑保护作用,初步显示了其疗效,其机制可能通过降低NF-κB起到脑保护作用.     

小鼠脑缺血再灌注早期核因子-κB活性的变化

目的 :研究脑缺血再灌注 (brainischemia reperfusion ,I/R)早期核转录因子 κB(NF κB)活性变化及作用。方法 :采用小鼠脑缺血再灌注损伤模型 ,记录异常神经症状 (abnormalnervoussymptoms,ANS) ,用RT PCR技术和免疫组织化学法分别检测脑缺血再灌注后不同时期NF κB亚单位P6 5及其抑制因子κBα(I κBα)的mRNA和蛋白表达。结果 :小鼠脑缺血再灌注后 30minP6 5蛋白活性增加 ,2h达高峰 ,2 4h仍维持较高水平 (均P <0 .0 5 ) ,而NF κBP6 5mRNA的表达无明显改变 (均P <0 .0 5 ) ;I κBα蛋白量于再灌注后 30min下降 ,2h达最低 (均P <0 .0 5 ) ,以后逐渐恢复正常 ,I κBαmRNA的表达与其蛋白表达相一致 (r =0 .75 1;P <0 .0 5 ) ;P6 5蛋白活性与异常神经症状呈正相关 (r =0 .795 ;P <0 .0 5 ) ,I κBα的蛋白及其mRNA的表达与异常神经症状均呈负相关 (r蛋白= 0 .75 2 ;rmRNA= 0 .70 9,均P <0 .0 5 )。结论 :小鼠脑缺血再灌注损伤早期脑组织神经细胞中存在NF κBP6 5的激活及其I κBα的减少 ;NF κB的激活可能参与了脑缺血再灌注早期的损伤过程。     

替米沙坦预处理对大鼠缺血再灌注损伤后心肌细胞凋亡及NF-κB表达的影响

目的研究替米沙坦预处理对大鼠心肌缺血再灌注损伤（MIRI）后心肌细胞凋亡及核转录因子κB（nuclear factor-kappa B,NF-κB）蛋白表达的影响。方法健康雄性SD大鼠32只,随机分为4组：假手术组（Sham组）、缺血再灌注组（MIRI组）、替米沙坦预处理Ⅰ组（TⅠ组）和替米沙坦预处理Ⅱ组（TⅡ组）,每组8只。TⅠ组灌胃替米沙坦5.0mg/（kg.d）,TⅡ组灌胃替米沙坦10.0mg/（kg.d）,其余每日灌胃等量生理盐水,持续一周。建立MIRI模型,光镜下观察心肌形态改变、测定血清CK-MB活性、TUNEL检测凋亡细胞及免疫组化测定NF-κBp65的表达。结果与Sham组相比,MIRI组与TⅠ、TⅡ组血清CK-MB活性、凋亡细胞、NF-κBp65表达明显升高（P〈0.01）;与MIRI组相比,TⅠ组血清CK-MB活性明显降低（P〈0.01）,凋亡细胞、NF-κBp65表达降低（P〈0.05）;TⅡ组血清CK-MB活性,凋亡细胞、NF-κBp65表达明显降低（P〈0.01）。结论替米沙坦预处理可降低心肌缺血再灌注血清CK-MB的含量,抑制NF-κBp65的表达,抑制细胞凋亡,对大鼠急性心肌缺血再灌注损伤起保护作用,而高剂量组的保护作用优于低剂量组。     

人参二醇组皂苷对四氯化碳所致大鼠急性肝损伤的 保护作用及其机制

目的：探讨人参二醇组皂苷（PDS）对四氯化碳（CCl₄）所致急性肝损伤（ALD）大鼠的保护作用,并阐明其作用机制。方法：50只大鼠随机分为对照组（给予生理盐水）,模型组（制备ALD模型,给予生理盐水）,低、中和高剂量PDS组（制备ALD模型,给予10、20和40 mg·kg^-1PND）,每组10只。观察各组大鼠一般状态;检测各组大鼠谷氨酸氨基转氨酶（ALT）、天门冬氨酸氨基转移酶（AST）、总胆红素（TBIL）和总蛋白（TP）水平;ELISA法测定各组大鼠肝组织匀浆中白细胞介素12（IL-12）、白细胞介素6（IL-6）和肿瘤坏死因子α（TNF-α）水平;Western blotting法检测各组大鼠肝组织中蛋白激酶B （又称AKT）和磷酸化蛋白激酶B （p-AKT）蛋白表达水平。结果：与对照组比较,模型组大鼠一般状态差,ALT、AST和TBIL水平明显升高（P<0.01）,TP水平降低（P<0.01）,IL-12、IL-6和TNF-α水平均明显升高（P<0.01）。与模型组比较,各剂量PDS组大鼠肝功能明显改善,ALT、AST和TBIL水平降低（P<0.01）,TP水平升高（P<0.01）,IL-12、IL-6和TNF-α水平降低（P<0.01）,肝组织中AKT蛋白表达水平降低（P<0.01）,p-AKT蛋白表达水平升高（P<0.01）。结论：PDS对ALD具有保护作用,其机制可能与降低炎症因子的表达、影响p-AKT-AKT信号通路有关。     

重组干扰素α治疗重症急性胰腺炎效果观察

目的探讨重组干扰素α对重症急性胰腺炎（SAP）的治疗作用及机制。方法将84例SAP患者随机分为临床干预组与对照组,对照组予以胃肠减压、预防感染、纠正水电解质平衡紊乱等常规治疗,干预组在常规治疗措施基础上肌注重组干扰素α40μg/d,7～14 d。观察治愈天数、发生并发症例数和病死例数,采用急性生理学及慢性健康状况评分-Ⅱ评分和CT评分评价病情。酶联免疫吸附法检测患者血清中肿瘤坏死因子-α（TNF-α）、白细胞介素-8（IL-8）、白细胞介素-2（IL-2）、白细胞介素-10（IL-10）和核因子кB浓度的变化。结果干预组较对照组治愈天数、发生并发症例数和病死例数有所降低,急性生理学及慢性健康状况评分-Ⅱ评分和CT评分显著降低。干预组TNF-α、IL-8和核因子кB较干预前下降,IL-2升高,IL-10升高后又回降。结论重组干扰素α在治疗SAP过程中,可减轻炎性反应、减少严重并发症发生、促进治愈。