NF-κB在动脉粥样硬化中的始动作用

动脉粥样硬化是一种具有慢性炎症反应的病理过程 ,血管内皮细胞在引发和扩大炎症反应中起了重要作用 ,以NF κB家族为调控中心的内皮细胞活化及炎症诱导有可能成为动脉粥样硬化形成的共同途径 ,选择性保护内皮细胞 ,可能为治疗动脉粥样硬化提供新的途径。     

黄芩苷经TLR2/NF-κB途径减轻类风湿关节炎大鼠滑膜炎

目的评价不同剂量黄芩苷对SD大鼠类风湿关节炎的疗效,并探讨其可能的作用机制。方法制备SD大鼠类风湿关节炎模型,测量后足的肿胀度;通过不同剂量黄芩苷溶液灌胃治疗后,观察膝关节滑膜HE染色切片病理变化;实时荧光定量PCR测定膝关节滑膜组织TLR2及MyD88mRNA表达;Westernblot测定滑膜组织TLR2、MyD88及NF-κBp65蛋白表达。结果黄芩苷30、60mg·kg~(-1)均能明显减弱滑膜组织中成纤维细胞的增殖及炎性损伤程度,明显降低滑膜组织TLR2及MyD88mRNA表达(P<0.01),明显减弱TLR2、MyD88及NF-κBp65蛋白表达(P<0.05)。结论黄芩苷具有良好的抗类风湿关节滑膜炎作用,其可能是通过抑制TLR2-NF-κB信号通路的活化来实现的。     

宝华玉兰种子提取物对NF-κB及IκBα表达的抑制作用

目的探讨宝华玉兰种子提取物对核转录因子-κB(NF-κB)、核转录因子-κB抑制蛋白α(IκBα)表达的抑制作用机制。方法使用宝华玉兰种子提取物处理人肝癌细胞HepG2后,用Western blotting法检测NF-κB及IκBα蛋白的表达变化情况。结果宝华玉兰种子提取物对IκBα的磷酸化及降解有抑制作用。宝华玉兰种子提取物可有效抑制NF-κB介导的基因转录。结论宝华玉兰种子提取物可能通过抑制IκBα磷酸化及降解,阻断NF-κB活性,进而抑制COX-2而发挥其抗炎和抗肿瘤作用。     

Hp相关性萎缩性胃炎中NF-κB p65蛋白及bcl-2蛋白的表达

目的探讨Hp相关性萎缩性胃炎中NF-κB p65蛋白及bcl-2蛋白的表达。方法选取Hp阳性萎缩性胃炎80例、Hp阴性46例,比较两组患者NF-κB p65蛋白、bcl-2蛋白阳性细胞百分率。结果 Hp阳性组NF-κB p65蛋白阳性细胞百分率、bcl-2蛋白阳性细胞百分率均高于Hp阴性组,差异均具有统计学意义(P<0.01)。结论 Hp相关性萎缩性胃炎中NF-κB p65蛋白及bcl-2蛋白的表达均呈上调趋势。     

雷公藤多苷片对溃疡性结肠炎小鼠结肠黏膜TLR4和NF-κB表达的影响

目的 观察雷公藤多苷片对右旋葡聚糖硫酸钠(dextran sulphate sodium,DSS)诱导的小鼠溃疡性结肠炎(ulcerative colitis,UC)模型结肠黏膜LPS/TLR4信号通路表达的影响,探讨其治疗UC的可能作用机制。方法 BALB/c小鼠随机分为6组：模型对照组,雷公藤多苷低、中、高剂量组、阴性对照组和正常对照组。采用葡聚糖硫酸钠复制UC小鼠模型,雷公藤多苷片混悬液灌胃给药21?d后,采用RT-PCR法检测TLR4 mRNA和蛋白的表达;采用Western Blot法测定NF-κB p65磷酸化水平;结肠组织冰冻切片进行免疫荧光双重染色,激光共聚焦显微镜观察NF-κB表达及分布。结果 雷公藤多苷各组较模型对照组TLR4表达水平显著降低(P<0.01),中、高剂量组、阴性对照组与正常对照组比较,差异无统计学意义。与模型对照组比较,低剂量组NF-κB p65磷酸化水平略有下降,中、高剂量组下降明显,但差异均无统计学意义。结论 雷公藤多苷片能够通过抑制LPS/TLR4信号通路的表达,抑制UC小鼠的炎症反应,对UC发病起到一定的保护作用。     

己酮可可碱对小鼠溃疡性结肠炎NF-κB的影响

目的:观察己酮可可碱(pentoxifylline,PTX)治疗小鼠溃疡性结肠炎(ulcerative colitis,UC)的治疗作用,探讨PTX对三硝基苯磺酸(TNBS)诱导的小鼠UC NF-κB的影响.方法:用TNBS局部灌肠法建立小鼠UC模型,随机分为正常组、模型组、PTX组、柳氮磺胺吡啶(SASP)组,评价疾病活动指数(DAI),观察结肠组织学损伤,用ELISA法测定结肠组织NF-κB的水平.结果:用TNBS灌肠可使小鼠结肠炎性改变;PTX治疗可使小鼠疾病活动指数、结肠黏膜大体形态学损伤评分及组织学评分、结肠黏膜组织NF-κB的表达明显下降,与SASP相比较差异无统计学意义(P＞0.05).结论:PTX对以TNBS诱发的小鼠UC有良好的治疗作用,其作用机制可能是通过抑制小鼠结肠黏膜组织NF-κB的表达而减轻其炎症性损害.     

泻心汤有效组分不同配伍对内毒素肺损伤大鼠NF-κB及IκB表达的影响

目的研究泻心汤有效组分及其配伍对内毒素肺损伤大鼠NF-κB及IκB表达的影响。方法大鼠灌胃给予黄芩总黄酮提取物(TFL)、大黄总游离蒽醌提取物(TFA)、大黄总结合蒽醌提取物(TCA)、TFL与TFA配伍高、低剂量(A高A低)、TFL与TCA配伍(B)及醋酸地塞米松(Dex)4d,末次给药后1h股静脉注射脂多糖(LPS)建立大鼠内毒素肺损伤模型,1、2、4h各组分别处死6只动物,收集肺组织,免疫印记(Western blot)检测核因子κB(NF-κB)、κB抑制因子(IκB)的蛋白表达。结果大黄总游离蒽醌、A高及Dex在1、2、4h均能够明显抑制NF-κB p65的核转位(P<0.01),所有给药组在2、4h均能够明显抑制胞质中的IκBα的降解(P<0.01)。结论泻心汤有效组分及其配伍对内毒素肺损伤大鼠保护作用与抑制NF-κB的核转位及IκB的降解有关。     

环烯醚萜苷对大鼠脑梗死后NF-κB与凋亡调节因子Bcl-2/Bax表达变化的影响

目的观察光化学法诱导大鼠脑梗死形成过程中核转录因子(Nuc lear factor-kappa B,NF-κB)与凋亡调节因子Bax和Bc l-2表达的变化,并探讨山茱萸环烯醚萜苷(iridoid gly-coside,IG)对这一过程的影响。方法大鼠预先灌胃给药7d后,制作光化学致脑梗死模型,采用免疫组织化学法检测脑组织中NF-κB表达的变化,W estern b lot技术检测凋亡调节因子Bax和Bc l-2表达的变化。结果模型组与对照组相比,脑皮层内NF-κB和Bax蛋白表达增多,Bc l-2蛋白表达减少。与模型组相比,IG能够明显的减少NF-κB和Bax蛋白表达,增高Bc l-2蛋白的表达。结论IG可通过影响脑内NF-κB和凋亡调节基因的表达而发挥对脑梗死的治疗作用。     

洋甘菊总黄酮通过抑制ACC/FAS/DGAT2通路减少ApoE-/-小鼠三酰甘油合成

目的： 探究洋甘菊总黄酮通过调节ACC/FAS/DGAT2通路减少ApoE^-/-小鼠三酰甘油合成的药理作用机制。方法： 用乙醇回流提取和大孔树脂分离纯化法获得洋甘菊总黄酮;高脂饲料喂养法建立ApoE^-/-小鼠高脂模型;以C57BL/6J小鼠为空白对照组,ApoE^-/-小鼠分成模型组,非诺贝特组（30 mg·kg^-1）,洋甘菊总黄酮低、中、高剂量组（88,176,352 mg·kg^-1）;空白对照组和模型组分别用基础饲料和高脂饲料喂养,其余组小鼠高脂饲料喂养的同时灌胃给药干预8周。检测小鼠血清三酰甘油（TG）、总胆固醇（TC）、高密度脂蛋白胆固醇（HDL-C）、低密度脂蛋白胆固醇（LDL-C）水平;HE染色和油红O染色观察小鼠肝脏脂肪变性情况;免疫组化法检测二酰基甘油酰基转移酶2（DGAT2）蛋白表达水平;Western Blot法检测肝组织乙酰辅酶A羧化酶（ACC）、脂肪酸合成酶（FAS）、DGAT2蛋白表达水平。结果： 与空白对照组相比,模型组小鼠TG、TC、LDL-C、ACC、FAS、DGAT2水平均明显升高,HDL-C水平明显降低;与模型组相比,非诺贝特组和洋甘菊总黄酮各剂量组脂肪变性情况明显减轻。与模型组相比,非诺贝特组、洋甘菊总黄酮各剂量组TG、TC、LDL-C、ACC、FAS水平均明显降低,HDL-C水平明显升高;非诺贝特组和洋甘菊总黄酮中、高剂量组DGAT2水平明显降低。结论： 洋甘菊总黄酮可以抑制ApoE^-/-小鼠三酰甘油合成,改善血脂水平,可能与其下调ACC/FAS/DGAT2通路表达有关。     

黄芩苷对大鼠心肌缺血再灌注损伤的保护作用

目的研究黄芩苷对大鼠缺血再灌注损伤的保护作用. 方法结扎大鼠左冠脉前降支40 min 再灌注120 min ,观察黄芩苷对心肌梗死后大鼠心功能、心肌梗死面积和乳酸脱氢酶(LDH)活性、丙二醛(MDA)含量、超氧化物歧化酶(SOD)活性等的影响.结果结扎冠脉前5 min给黄芩苷10～40 mgkg-1能改善心肌梗死后大鼠的心功能、减少心肌梗死面积(9%～30%),并能减少梗死后心肌MDA含量、提高梗死后心肌SOD、 LDH的活性. 结论黄芩苷对大鼠缺血再灌注的心肌损伤有保护作用.     

黄芩苷对大鼠心肌缺血再灌注损伤的保护作用

目的　研究黄芩苷对大鼠缺血再灌注损伤的保护作用。方法　结扎大鼠左冠脉前降支 4 0min再灌注 12 0min ,观察黄芩苷对心肌梗死后大鼠心功能、心肌梗死面积和乳酸脱氢酶 (LDH)活性、丙二醛 (MDA)含量、超氧化物歧化酶(SOD)活性等的影响。结果　结扎冠脉前 5min给黄芩苷10～ 4 0mg·kg-1能改善心肌梗死后大鼠的心功能、减少心肌梗死面积 (9%～ 30 % ) ,并能减少梗死后心肌MDA含量、提高梗死后心肌SOD、LDH的活性。结论　黄芩苷对大鼠缺血再灌注的心肌损伤有保护作用     

Vitamin D improves hepatic alterations in ACE1 and ACE2 expression in experimentally induced metabolic syndrome

Metabolic Syndrome (MetS) is a term used to describe a cluster of pathophysiological, biochemical, and metabolic criteria; including high Blood Pressure (BP), high cholesterol, dyslipidaemia, central obesity and Insulin Resistance (IR). The Renin Angiotensin System (RAS) has a regulatory function in BP, hydroelectrolyte balance, and cardiovascular function. RAS is composed of angiotensinogen (AGT), (Ang I), (Ang II), (ACE1), (ACE2), (AT1R), (AT2R), and (Ang 1–7). Vitamin D had been proved to act as a protective factor against MetS. Therefore, the study is pursued to explore vitamin D supplementation roles on hepatic RAS in MetS experimental model. At first, 36 males Albino rats were separated into 4 groups and induced to MetS under controlled circumstances for 3 months. Then, data were collected from blood samples, whereas RNA extracted from liver were analyzed using biochemical and statistical analysis tests. As a result, the major finding was proving that vitamin D can balance the expression of ACE1 and ACE2. Also, confirming that it can improve MetS components by elevating HDL and insulin levels while reducing the levels of BP, cholesterol, LDL, TG, GLU, ALT, AST, and IR. These outcomes may give a new insight into the RAS pathways associated with MetS.     

Protective effects of ACE inhibitors on vascular endothelial dysfunction induced by exogenous advanced oxidation protein products in rats

To explore detrimental effects of advanced oxidation protein products-bovine serum albumin (BSA) on endothelial function and compare the favorable effects of angiotensin-converting enzyme (ACE) inhibitors: captopril and enalapril. Male Sprague-Dawley rats were randomly divided into groups: control, advanced oxidation protein products-BSA, captopril (10, 20 mg/kg/day), enalapril (15 mg/kg/day), and N(G)-nitro-l-arginine methyl ester (l-NAME, 300 mg/kg/day) plus captopril (20 mg/kg/day) groups. All animals were given advanced oxidation protein products-BSA (100 mg/kg/day, i.v.) except for control group (iv. equal volume of PBS). Rats in other groups were received different drugs intragastrically after advanced oxidation protein products-BSA administration. Endothelium-dependent relaxation of thoracic aorta was assayed. Content of nitrite/nitrate (NO), malondialdehyde (MDA), activities of glutathione peroxidase (GSH-Px), superoxide dismutase (SOD) and of ACE in Sera, as well as renal function index including blood urea nitrogen and creatinine were measured. After 30 days, the endothelium-dependent relaxation of blood vessels in received advanced oxidation protein products-BSA rats was significantly impaired compared with control rats. The impairment was accompanied by decreases of serum NO, activity of GSH-Px and SOD. Administration of captopril and enalapril not only decreased damage of endothelium-dependent relaxation, but also reverse the changes of MDA levels, NO content and activity of SOD. The protective effect of captopril was abolished by L-NAME. Blood urea nitrogen and creatinine had no significant differences between various groups. ACE activities were decreased in high captopril and enalapril groups, but did not significantly change in other groups. The results suggested that captopril and enalapril have similar effects on endothelial dysfunction induced by advanced oxidation protein products-BSA, which indicated that protective effects of captopril are not related to sulfhydryl group.     

氯沙坦对大鼠心肌缺血后心脏ACE2蛋白表达的影响

目的探讨氯沙坦对心肌缺血大鼠心肌组织中ACE2表达水平的影响。方法 SPF级健康雄性SD大鼠60只(体重220²40 g),通过部分结扎冠状动脉前降支建立大鼠心肌缺血模型,将术后24 h存活的42只大鼠随机分为14 d模型组、28 d模型组、14 d氯沙坦大剂量组、14 d氯沙坦小剂量组、28 d氯沙坦大剂量组、28 d氯沙坦小剂量组、假手术组,每组6只。术后24 h开始灌胃给药,小剂量氯沙坦组10 mg/(kg·d)灌胃给药,大剂量氯沙坦组30 mg/(kg·d)灌胃给药,假手术组及模型组给予等量生理盐水灌胃;分别于用药14 d、28 d后,行HE染色,明确心肌组织缺血病变情况,Western blot法检测左心室缺血区心肌组织ACE2蛋白表达的水平。结果模型组大鼠缺血心肌组织中ACE2蛋白表达量较假手术组升高(P<0.01),呈时间依赖性。氯沙坦剂量依赖性增加ACE2蛋白的表达量(P<0.05)。结论氯沙坦可增加心肌缺血后大鼠心肌组织中ACE2的表达量,进一步改善心肌缺血状态。     

百草枯中毒大鼠肺组织ACE/ACE2表达变化及贝那普利的干预作用

目的观察贝那普利对百草枯(PQ)中毒大鼠肺组织病理改变、血管紧张素转化酶(ACE)及其同源物ACE2表达的影响。方法一次性PQ 60mg.kg-1灌胃建立大鼠百草枯中毒肺纤维化模型,干预组染毒后加予贝那普利10mg/(kg.d)灌胃。于染毒后第三、七、二十一天取肺组织行HE染色和Masson染色,观察大鼠肺泡炎、肺纤维化程度;免疫组化测Ⅰ、Ⅲ型胶原;Quantitative real-time PCR检测ACE、ACE2 mRNA表达;ELISA检测肺组织AngⅡ蛋白表达。结果干预组在染毒后3d、7d肺泡炎症减轻;染毒7d后,纤维化程度积分、胶原Ⅰ、胶原Ⅲ含量低于模型组。模型组染毒后各时间点大鼠肺组织ACE mRNA及AngⅡ蛋白表达逐步上调,持续至21d;第七天后ACE2 mRNA的表达降低。干预组各时间点ACE mRNA及AngⅡ蛋白低于模型组,第七天后ACE2 mRNA表达上调。结论贝那普利可能通过降低局部ACE表达或促进ACE2合成,抑制AngⅡ生成,从而减轻百草枯中毒所致肺纤维化形成。     

溴氰菊酯对大鼠脑组织CYP2B1/2B2蛋白表达的影响

目的　研究CYP2B1 2B2在大鼠脑组织中的分布及溴氰菊酯 (DM)对大鼠脑组织中苄氧基试卤灵O 脱烷基化酶 (BROD)酶活力及CYP2B1 2B2蛋白表达的影响。方法　采用荧光分光光度法 ,在体内、体外研究了DM对大鼠脑组织中BROD活力的影响 ,并用免疫组织化学方法检测了在大鼠脑组织中的分布及CYP2B1 2B2和DM对蛋白表达的影响。结果　大鼠DM12 5mg (kg·d)腹腔注射连续 5d染毒后 ,大脑皮层及小脑RDBO活力明显被抑制 ,差异具有显著性 (P <0 0 5 ) ;在体外 ,DM浓度在 (2× 10 - 8～ 2× 10 - 4)mol L范围内对BROD活力无明显影响 ;DM在体内明显抑制小脑及大脑皮层中CYP2B1 2B2蛋白表达。结论　CYP2B1 2B2在大鼠脑组织中分布有差异 ,DM在体内能明显抑制脑内RDBO活力 ,其机制与抑制该酶蛋白合成有关     

The effects of protein stabilizers on aggregation induced by multiple-stresses

A successful development of therapeutic proteins requires a formulation optimal for long-term storage of the proteins. During storage and shipment, proteins are subjected to multiple stresses. Here we show that ciliary neurotrophic factor (CNTF) readily aggregates upon exposure to mechanical stress such as agitation and elevated temperature at 37 degrees C. Sucrose and lysine or arginine protect CNTF from heat stress, while detergents such as Tween20 and organic solvents such as propylene glycol (PG) are effective against agitation. Combination of the amino acids and PG protected the protein from both stresses. The results suggest the importance of combining additives, against multiple stresses, which may have negative as well as positive influence individually against one particular stress.     

Sympatholytic drugs and hyperlipaemia induced in rats by intraperitoneal injections of surface-active agent

Hyperlipaemia and hypercholesterolaemia were induced in white rats by intraperitoneal injections of tyloxapol. Various sympatholytics and adrenolytics, including blocking agents of β-receptors, were given simultaneously with tyloxapol. Bretylium tosylate prevented the increase in the serum levels of esterified fatty acids and cholesterol caused by tyloxapol. Phentolamine decreased the enhancement by tyloxapol of cholesterol and total lipid concentrations in the serum. Guanethidine and phenoxybenzamine reduced the increase in the concentration of esterified fatty acids, whereas dichloroisoprenaline insignificantly increased the tyloxapol-induced hyperlipaemia. A small dose of pronethalol slightly increased the esterified fatty acid level in tyloxapol-treated animals; a large dose significantly decreased the serum cholesterol concentration.