吡格列酮对脂多糖诱导的星形胶质细胞炎性细胞因子释放的影响

目的研究吡格列酮对脂多糖(LPS)诱导的星形胶质细胞炎症介质释放的抑制作用及其信号传导通路。方法神经胶质酸性蛋白(glial fibrillary acid protein,GFAP)免疫荧光染色法鉴定星形胶质细胞纯度。ELISA方法检测IL-1β、IL-6和TNF-α蛋白表达量的变化。Griess法测定培养细胞上清液中一氧化氮(NO)含量。结果星形胶质细胞经GFAP免疫荧光鉴定,其阳性率可达95%以上。LPS组能明显增加星形胶质细胞分泌IL-1β、IL-6、TNF-α及NO。吡格列酮能明显抑制LPS引起的这些作用,并呈一定浓度依赖性。过氧化物酶体增殖物激活受体γ(PPARγ)的特异性阻断剂GW9662能明显对抗吡格列酮对LPS引起的IL-1β、IL-6、TNF-α及NO增加的抑制作用。与LPS组相比,JNK特异性阻断剂SP600125(5μmol·L-1)亦能有效对抗LPS诱导星形胶质细胞IL-1β、IL-6、TNF-α及NO分泌的增加;特异性iNOS抑制剂SMT可明显抑制LPS引起的NO分泌增加。结论吡格列酮能明显改善LPS诱导的大鼠皮层星形胶质细胞的损伤,这种作用可能与激活PPARγ、抑制JNK信号传导通路有关。     

卡巴胆碱对内毒素刺激大鼠腹腔巨噬细胞炎症细胞因子表达的影响

目的:研究拟胆碱药卡巴胆碱在体外对内毒素(LPS)刺激大鼠腹腔巨噬细胞表达炎症细胞因子的作用.方法:采集雄性Wistar大鼠腹腔巨噬细胞,经卡巴胆碱、烟碱或毒蕈碱预处理后,再给予LPS刺激,4 h后取细胞培养上清液,ELISA法检测TNF-α、IL-6和IL-10水平.结果:LPS刺激后TNF-α、IL-6和IL-10表达均显著增加.卡巴胆碱与烟碱能明显抑制TNF-α、IL-6表达的增加(P<0.01),卡巴胆碱的抑制作用有明显的量效关系,毒蕈碱的抑制作用则明显低于卡巴胆碱和烟碱(P<0.01).卡巴胆碱和烟碱对LPS刺激后的IL-10水平升高均无明显影响.结论:卡巴胆碱在体外LPS刺激腹腔巨噬细胞炎症模型中能抑制促炎细胞因子表达的增加而对抗炎细胞因子表达无明显作用,其作用与烟碱类似.     

吡格列酮体外对大鼠心肌肥大的改善作用

目的　探讨噻唑烷二酮 (TZD)类药物吡格列酮在体外对心肌肥大的影响。方法　新生大鼠的原代培养心肌细胞和非心肌细胞 ,以血管紧张素Ⅱ (AngⅡ )刺激建立体外心肌肥大模型 ,并用不同浓度的吡格列酮作用细胞。采用RT PCR法检测心肌肥大特征性基因心钠肽 (ANP)和脑钠肽(BNP)的mRNA表达 ,以MTT比色法和3 H TdR参入实验检测非心肌细胞增殖情况 ,以3 H 亮氨酸参入实验检测心肌细胞蛋白合成速率 ,并用软件分析心肌细胞表面积。结果　肥大模型出现后 ,心肌细胞表面积、ANP和BNP的mRNA表达以及蛋白合成速率增加 ;非心肌细胞增殖活跃 ,但ANP和BNP的mRNA表达没有变化。吡格列酮可以逆转这些变化 ,同时下调非心肌细胞的ANP和BNP的mRNA表达 ,并呈一定的剂量依赖性。结论　吡格列酮体外对大鼠心肌肥大有改善作用 ,预示着TZD类药物具有防治心肌肥大等心血管疾病的药理作用     

Urotensin-II-mediated cardiomyocyte hypertrophy: effect of receptor antagonism and role of inflammatory mediators

Urotensin-II (U-II), the most potent mammalian vasoconstrictor identified, and its receptor, UT, exhibits increased expression in cardiac tissue and plasma in congestive heart failure (CHF) patients. Cardiomyocyte hypertrophy is primarily responsible for increased myocardial mass associated with cardiac injury. Neurohumoral factors such as angiotensin-II, endothelin-1, catecholamines, and inflammatory cytokines are thought to mediate this response. U-II shares similar biological activities with other hypertrophic G_q-coupled receptor ligands such as angiotensin-II and endothelin-1, but a role for U-II in cardiomyocyte hypertrophy has not been characterized. The hypothesis of the current study was that U-II, acting through its G_q-coupled receptor UT plays a hypertrophic role in cardiac hypertrophic remodeling. We report that adenoviral upregulation of the UT receptor unmasked U-II-induced hypertrophy in H9c2 cardiomyocytes, with a threshold response of 202±8 binding sites/cell. U-II was equally as efficacious as phenylephrine in inducing hypertrophy, measured by a reporter assay (EC₅₀ 0.7±0.2 nM) and [³H]-leucine incorporation (EC₅₀ 150±40 nM). A competitive peptidic UT receptor antagonist, BIM-23127, inhibited U-II-induced hypertrophy (K_B 34±6 nM). U-II did not affect cell proliferation or apoptosis, indicating that U-II is more hypertrophic than apoptotic or hyperplastic in cardiomyocytes. U-II (10 nM) stimulated interleukin-6 release in UT-expressing cardiomyocytes (4.6-fold at 6 h). Finally, in a rat heart failure model, cardiac ventricular mRNA expression of U-II, UT receptor, interleukin-6, and interleukin-1- is increased time-dependently following myocardial injury. These results indicate that U-II might play a role in cardiac remodeling associated with CHF by stimulation of cardiomyocyte hypertrophy via UT, and through upregulation of inflammatory cytokines. As such, UT antagonism may represent a novel therapeutic target for the clinical management of heart failure.     

维药异叶青兰总黄酮对去甲肾上腺素诱导的大鼠心肌细胞肥大的影响

目的研究维药异叶青兰总黄酮(TFDH)对去甲肾上腺素(NE)诱导的心肌细胞肥大的作用,并探讨其作用机制。方法以原代培养的新生大鼠心肌细胞与TFDH 10,25和50μmol·L~(-1)孵育30 min后,加入NE 2μmol·L~(-1)共培养48 h。CCK-8法观察心肌细胞存活率;RT-PCR法检测心肌肥大基因心房利钠肽(ANP)和β-肌球蛋白重链(β-MHC)的m RNA表达水平;激光共聚焦法检测心肌细胞的表面积和细胞内钙离子浓度([Ca~(2+)]_i);破碎细胞后酶促反应测定Ca~(2+)-ATP酶的活性;比色法测定一氧化氮(NO)浓度和一氧化氮合酶(NOS)活性。结果与细胞对照组相比,NE 2μmol·L~(-1)刺激心肌细胞48 h,可使心肌细胞相对存活率由细胞对照组的(95±1)%下降至(78±5)%(P<0.05);细胞表面积由(178±29)μm~2显著增加至(274±38)μm~2(P<0.05);ANP和β-MHC m RNA相对表达水平显著上调,分别由细胞对照组的1.00±0.01和1.00±0.02升高至2.76±0.55和2.69±0.31(P<0.05);心肌细胞内[Ca~(2+)]_i显著升高,由细胞对照组的(1.00±0.12)升高至(1.52±0.41)μmol·L~(-1),Ca~(2+)-ATP酶的活性显著下调,由细胞对照组的(1.01±0.14)下降至(0.41±0.06)μmol·L~(-1)(P<0.05);NO浓度由细胞对照组的(1.50±0.14)下降至(1.12±0.05)μmol·L~(-1),NOS活性由细胞对照组的(0.86±0.06)下降至(0.52±0.10)μmol·L~(-1)(P<0.05)。给予TFDH 10~50μmol·L~(-1)能对抗NE引起的心肌细胞存活率下降和表面积增大,对NE引起的ANP和β-MHC m RNA表达增加也有一定抑制作用(P<0.05),同时对心肌细胞内[Ca~(2+)]_i升高、Ca~(2+)-ATP酶活性下降及NO浓度和NOS活性下降也具有一定的对抗作用(P<0.05)。结论TFDH能改善NE诱导的心肌细胞肥大,提高心肌细胞存活率,下调ANP和β-MHC m RNA的表达,减小心肌细胞表面积,其机制可能与促进NO释放、调节细胞内Ca~(2+)浓度和a~(2+)-ATP酶活性有关。     

过表达SOCS2对人肾小球系膜细胞中炎性因子表达的影响及其机制研究

目的 建立过表达SOCS2的HMCs细胞模型,检测各组HMCs中JAK/STAT信号通路的活性,观察DN炎性因子的表达,明确过表达SOCS2对细胞模型的影响及作用机制。方法 通过腺病毒感染的方法使细胞模型中过表达SOCS2,实验分为CG组、CG+Ad-null组、CG+Ad-SOCS2组、HG组、HG+Ad-null组、HG+Ad-SOCS2组。Western blot方法检测各组细胞模型中JAK/STAT信号通路的活化情况。ELISA方法检测各组细胞培养上清中IL-6、TNF-α的表达。结果 与CG组相比,高糖诱导后的HG组、HG+Ad-null组、HG+Ad-SOCS2组中p-JAK2、P-STAT3、IL-6、TNF-α的表达量均升高(P<0.01);与HG组相比,HG+Ad-SOCS2组中这些指标均显著下降(P<0.01),而HG+Ad-null组则无显著差异。结论 SOCS2通过抑制JAK/STAT信号通路来降低细胞模型中炎性因子IL-6、TNF-α的表达。     

丹参酮IIA磺酸钠对血管紧张素II诱导的心肌肥大及p-ERK表达的影响

目的:观察丹参酮IIA磺酸钠(STS)对血管紧张素II(Ang II)诱导的心肌肥大及p-ERK表达的影响。方法:培养新生大鼠心肌细胞,考马斯亮蓝法测定心肌细胞蛋白含量、[3H]-亮氨酸掺入法测定蛋白合成速率作为心肌肥大指标;用West-ern-blot测定p-ERK表达。结果:STS能显著降低Ang II诱导的心肌细胞总蛋白含量、蛋白合成速率上升,同时对p-ERK表达具有剂量、时间依赖性抑制作用。结论:STS可以抑制Ang II诱导的心肌肥大,机制与抑制p-ERK表达有关。     

吡格列酮对脂多糖引起的大鼠学习记忆障碍及海马炎症反应的影响

目的研究吡格列酮(pioglitazone,Pio)能否对抗脂多糖(lipopolysaccharide,LPS)所致的大鼠学习记忆障碍及海马炎症反应。方法取SD大鼠40只,随机分为4组:生理盐水对照组,LPS损伤组,LPS+Pio 40和80 mg.kg-1组。灌胃给予Pio 2 d后,脑室注射LPS 5μl(1.0 mmol·L-1),生理盐水对照组注射等量生理盐水。脑室注射后d 2进行Morris定位航行实验,连续5 d,在d 6进行空间探索实验,训练期间继续给药。d 7,快速取海马CA1区,Western blot方法观察白介素-1β(Interleukin-1β,IL-1β),诱导型一氧化氮合酶(Inducible Nitric Oxide Synthase,iNOS),半胱氨酸天冬氨酸蛋白酶(caspase)3,caspase-9及多聚ADP-核糖聚合酶(PARP)蛋白表达水平的变化。RT-PCR检测IL-1β和iNOS的mRNA表达水平。结果脑室内注射LPS,大鼠出现明显的空间学习记忆障碍,表现为逃避潜伏期较生理盐水对照组明显延长(P<0.05),在原平台象限游泳时间占总游泳时间的百分比明显降低(P<0.01)。Western蛋白印迹及RT-PCR结果显示注射LPS后,与对照组相比海马CA1区IL-1β、iNOS蛋白及mRNA表达水平明显增加(P<0.01),活化的caspase-3,caspase-9蛋白表达水平明显增高,分子质量116 ku PARP表达明显减少,而分子质量89 ku劈切PARP表达明显增加(P<0.01)。Pio(40和80 mg.kg-1)能改善大鼠学习记忆功能,对抗LPS引起的海马CA1区IL-1β、iN-OS、活化的caspase-3、活化的caspase-9表达增加,也可明显抑制LPS所致的PARP表达的改变(P<0.01)。结论吡格列酮能够改善大鼠学习记忆功能,抑制LPS引起的海马炎症反应。     

五甲基槲皮素预处理对大鼠心肌细胞缺氧复氧损伤保护作用的机制研究

目的 探讨五甲基槲皮素（PMQ）预处理对大鼠心肌细胞缺氧/复氧（A/R）损伤的保护作用及其线粒体功能的影响。方法 原代培养SD大鼠乳鼠心肌细胞,经终浓度分别为10,30,100 μmol·L-1 PMQ预处理24 h后,制作A/R损伤,检测培养液中乳酸脱氢酶（LDH） 活性、四唑盐（MTT）比色法检测细胞存活率、流式细胞法检测线粒体膜电位和细胞凋亡情况、线粒体肿胀法检测各组心肌细胞线粒体mPTP开放情况。结果 不同剂量PMQ（10, 30,100 μmol·L-1）预处理24 h后可剂量依赖性的降低LDH活性、增加细胞存活率、减少细胞凋亡（P 〈0.05或P 〈0.01）;30, 100 μmol·L-1 PMQ预处理24 h后,线粒体膜电位更为稳定、mPTP开放减少（P 〈0.05或P 〈0.01）。结论 PMQ预处理24 h后,可产生药理性延迟保护作用,机制与其稳定线粒体膜电位、抑制mPTP开放,进而减少细胞凋亡有关。     

Inhibitory effect of resveratrol on angiotensin II-induced cardiomyocyte hypertrophy

Resveratrol is proposed to account in part for the protective effect of red wine on the cardiovascular system. Angiotensin II (Ang II) is a potent hypertrophic stimulus in cardiomyocytes. In this study, we determined the effect of resveratrol on Ang II-induced cardiomyocyte hypertrophy. Cultured neonatal rat cardiomyocytes were stimulated with Ang II, and [³H]leucine incorporation and -myosin heavy chain (-MyHC) promoter activity were examined. Intracellular reactive oxygen species (ROS) were measured by a redox-sensitive fluorescent dye, 2 7-dichlorofluorescin diacetate, and the extracellular signal-regulated kinase (ERK) phosphorylation was examined by Western blotting. Resveratrol inhibited Ang II-increased intracellular ROS levels. Furthermore, resveratrol, as well as the antioxidant N-acetyl-cysteine, decreased Ang II- or H₂O₂-increased protein synthesis, -MyHC promoter activity, and ERK phosphorylation. In summary, we demonstrate for the first time that resveratrol inhibits Ang II-induced cardiomyocyte hypertrophy via attenuation of ROS generation.Abbreviations Ang II Angiotensin II - MAPKs Mitogen-activated protein kinases - ERK Extracellular signal-regulated kinase - JNK c-Jun N-terminal kinase - p38 MAPK p38 mitogen-activated protein kinases - MEK MAPK or ERK kinase - NAC N-acetylcysteine - DCF-DA Dichlorodihydrofluorescein diacetate - DCF Dichlorofluorescein     

Inhibitory effect of trilinolein on angiotensin II-induced cardiomyocyte hypertrophy

The myocardial protective effects of trilinolein, isolated from the Chinese herb Sanchi (Panax notoginseng), may be related to its antioxidant effects. In the present study, we investigated the effects of trilinolein on angiotensin II-induced cardiomyocyte hypertrophy. Cultured neonatal rat cardiomyocytes were stimulated with angiotensin II, [3H]leucine incorporation and the beta-myosin heavy chain promoter activity were examined. We also examined the effects of trilinolein on angiotensin II-induced intracellular reactive oxygen species generation. Trilinolein significantly inhibited angiotensin II-increased protein synthesis, beta-myosin heavy chain promoter activity, and intracellular reactive oxygen species generation. Antioxidant N-acetylcysteine also decreased angiotensin II-increased protein synthesis and beta-myosin heavy chain promoter activity. Furthermore, trilinolein and N-acetylcysteine decreased angiotensin II- or hydrogen peroxide (H2O2)-activated mitogen-activated protein kinases (MAPKs) phosphorylation, and activator protein-1 (AP-1)- [or nuclear factor-kappaB (NF-kappaB)]-reporter activities. These data indicate that trilinolein inhibits angiotensin II-induced cardiomyocyte hypertrophy and beta-myosin heavy chain promoter activity via attenuation of reactive oxygen species generation.     

吡格列酮对糖尿病大鼠肾组织podocalyxin表达的影响

目的观察不同剂量盐酸吡格列酮(PIO)对STZ诱导的糖尿病大鼠的肾脏保护作用及肾小球Podocalyxin(PCX)表达的影响方法链脲佐菌素(STZ)65 mg.kg-1腹腔注射后建立糖尿病大鼠模型后随机分为4组,分别为模型组(DM组,n=8)和不同剂量盐酸吡格列酮组(DR1、DR2、DR3组,PIO分别:10、20和30 mg.kg-1.d-1,各组n=8),并设正常对照组(NC组,n=8)。于0周及8周末测尿白蛋白(UAlb),尿视黄醇结合蛋白(URBP),尿沉渣PCX(UPCX)和尿肌酐(UCr)。每周监测血糖,8周末取血检测HbA1c,留取左肾观察病理变化,免疫组化及RT-PCR检测肾组织PCX蛋白及mRNA水平。结果①各组糖尿病大鼠各时间点血糖及8周末HbA1c明显高于NC组(均P<0.01),各糖尿病组间差异无统计学意义;②8周末DR1、DR2和DR3组UACR、URCR、肾脏肥大指数(KI)、基底膜厚度(GBMT)、足突融合率(FPFR)均明显低于DM组(均P<0.05),且DR2组和DR3组低于DR1组(均P<0.05);DR2组及DR3组UPCR明显低于DM组(P<0.01),DR1组轻度降低但差异无统计学意义;各PIO组肾组织PCX蛋白及mRNA水平明显高于DM组(P<0.01),且DR2组和DR3组PCX蛋白表达高于DR1组(P<0.05);③8周末,各糖尿病组大鼠Scr、BUN、TG、LDL-C均高于NC组,HDL-C低于NC组,各PIO组BUN、TG均明显低于模型组(P<0.05),DR2及DR3组HDL-C水平高于模型组(P<0.05)。④UPCR与UACR和KI呈正相关(r=0.86,r=0.833,P<0.01)。结论吡格列酮可减轻糖尿病大鼠肾脏损伤,该作用可能部分与其增加肾小球足细胞PCX蛋白和mRNA表达,抑制PCX随尿排泄有关,这一作用具有一定的剂量依赖性。     

吡格列酮联合厄贝沙坦对原发性高血压患者左心室肥厚及血清脑钠肽的影响

目的 探讨吡格列酮对原发性高血压患者左心室肥厚及脑钠肽的影响.方法 原发性高血压伴左心室肥厚患者80例完全随机分成2组,各40例.常规治疗组给予厄贝沙坦（150 mg/d）,吡格列酮组给予厄贝沙坦（150 mg/d）＋吡格列酮（15 mg/d）,均治疗6个月.比较2组治疗前后左心室质量指数（LV MI）、血清脑钠肽浓度的变化.结果 治疗后2组患者LVMI、血清脑钠肽浓度均下降（P＜0.05）,2组治疗后比较,吡格列酮组LVMI、血清脑钠肽浓度下降为[（126.2±10.4）g/m2、（113.6±42.9）ng/L,较常规治疗组[分别为（135.5±11.2）g/m2、（138.8±45.8）ng/L]明显（P＜0.05）.结论 吡格列酮能逆转高血压病患者的左心室肥厚,并降低血清脑钠肽浓度.     

吡格列酮对高脂喂养SD大鼠visfatin蛋白表达的影响

Visfatin由Fukuhlara等[1]2005 年发现,主要由内脏脂肪分泌.具有促进脂肪形成、降低血糖等类胰岛素作用,与肥胖、2型糖尿病有着密切联系.吡格列酮改善胰岛素抵抗的部分机制可能是通过调节脂肪因子的产生[2].本研究通过高脂喂养建立肥胖SD大鼠实验模型,用吡格列酮干预来观察其对visfatin表达的影响,探讨吡格列酮改善胰岛素敏感性的可能作用机制.     

Effect of matrine on the expression of substance P receptor and inflammatory cytokines production in human skin keratinocytes and fibroblasts

Matrine is a kind of alkaloid found in certain Sophora plants, which has been extensively used in China for the treatment of viral hepatitis, cancer, cardiac diseases and skin diseases (such as atopic dermatitis and eczema). It also has been confirmed that substance P (SP) and its receptor (neurokinin-1 receptor, NK-1R) are involved in the pathogenesis of inflammatory skin disorders. So the present study was designed to investigate the effect of matrine on the expression of NK-1R and cytokines production induced by SP in HaCaT cells (a human epidermal keratinocyte cell line) and dermal fibroblasts. In addition, cell viability was also evaluated. The results showed that matrine inhibited the expression of NK-1R in HaCaT cells and fibroblasts. SP induced the production of interleukin (IL)-1beta, IL-8, interferon (IFN)-gamma, and monocyte chemotactic protein (MCP)-1 in both cell types. Matrine 5-100 microg/mL had little effect on cell viability. It inhibited SP-induced IL-1beta, IL-8 and MCP-1 production in HaCaT cells and fibroblasts, while it increased the production of IFN-gamma in HaCaT cells. Both SP and matrine had no effect on the secretion of IL-6. These findings suggest that matrine may have potential treatment function on SP related cutaneous inflammation by inhibition of the expression of substance P receptor and regulation of the production of inflammatory cytokines.     

丹参酮ⅡA磺酸钠对血管紧张素Ⅱ诱导的心肌肥大及p-ERK表达的影响

目的：观察丹参酮ⅡA磺酸钠（STS）对血管紧张素Ⅱ（AngⅡ）诱导的心肌肥大及p-ERK表达的影响。方法：培养新生大鼠心肌细胞，考马斯亮蓝法测定心肌细胞蛋白含量、[H^3]-亮氨酸掺入法测定蛋白合成速率作为心肌肥大指标；用West—ern-blot测定p-ERK表达。结果：STS能显著降低AngⅡ诱导的心肌细胞总蛋白含量、蛋白合成速率上升，同时对p-ERK表达具有剂量、时间依赖性抑制作用。结论：STS可以抑制AngⅡ诱导的心肌肥大，机制与抑制p-ERK表达有关。     

Attenuating effects of dihydromyricetin on angiotensin II-induced rat cardiomyocyte hypertrophy related to antioxidative activity in a NO-dependent manner

Abstract

Context: Dihydromyricetin (DMY) displays a range of biological properties. However, whether DMY attenuates cardiomyocyte hypertrophy is unknown.

Objective: To investigate whether DMY had potential therapeutic value to protect against angiotensin II (Ang II)-induced cardiomyocyte hypertrophy.

Materials and methods: Neonatal rat cardiomyocytes were pretreated with DMY (0–320?μM) followed with Ang II (100?nM) stimulation for 24?h, and then degree of hypertrophy was evaluated by cell surface analysis. Levels of reactive oxygen species (ROS) were measured with 2′,7′-dichlorfluorescein-diacetate (DCFH-DA) fluorescent staining. Antioxidative activity was evaluated by malondialdehyde (MDA) level, superoxide dismutase (SOD) activity, and total antioxidant capacity (T-AOC). Cyclic guanosine monophosphate (cGMP) was determined with a radioimmunoassay.

Results: Pre-incubation with DMY (20, 40, 80, and 160?μM) for 8?h, 12?h, 24?h, or 48?h decreased cell surface areas. It down-regulated mRNA expression of atrial natriuretic factor (1.95- to 1.24-fold) and β-myosin heavy chains (3.51- to 2.32-fold), reduced levels of MDA as well as increased SOD activity and T-AOC. Expression of SOD and thioredoxin were enhanced by DMY, whereas p22^phox and phosphorylation of mitogen-activated protein kinases were inhibited. Content of cGMP (0.54- to 0.80-fold) and phosphorylation of endothelial nitric oxide synthase at serine 1177 (0.70- to 1.05-fold) were augmented by DMY. Moreover, attenuating effect of DMY on hypertrophy was abolished when NO production was inhibited by l-NAME.

Conclusion: Attenuating effects of DMY on Ang II-induced cardiomyocyte hypertrophy related to antioxidative activity in a NO-dependent manner.     

依达拉奉对急性脑梗死患者疗效及血清炎性细胞因子水平的影响

目的：观察依达拉奉对急性脑梗死患者血中细胞因子水平及疗效的影响。方法80例行微创碎吸术高血压脑出血患者术时间随机分为两组,每组40例,对照组采用常规治疗,观察组加用依达拉奉治疗,同时选10例健康人血清做健康对照,连续监测血清中肿瘤坏死因子α（TNF-α）、白细胞介素8（IL-8）的动态变化。治疗后第15天进行临床疗效评定。结果两组患者的TNF-α、IL-8含量均高于健康对照组。观察组患者其TNF-α、IL-8含量达峰时间早。对照组患者TNF-α、IL-8含量达峰时间较晚,且TNF-α、IL-8水平较高。与对照组相比,观察组患者总体有效率高。结论急性脑梗死患者予依达拉奉治疗可降低血清中TNF-α、IL-8水平,改善患者预后。     

槲皮素抗阿霉素诱导的培养心肌细胞的凋亡

目的观察槲皮素对阿霉素(adriamycin,ADR)致大鼠心肌细胞凋亡的影响。方法原代培养乳鼠心肌细胞,随机分为正常对照组、阿霉素损伤组、槲皮素对照组、阿霉素+槲皮素(低、中、高浓度)组。比色法检测培养液中乳酸脱氢酶(LDH)的活性,MTT法测定心肌细胞存活率,电镜观察细胞超微结构,免疫细胞化学法检测Bcl-2和Bax蛋白的表达,用RT-PCR和Western blot检测caspase-3 mRNA和蛋白的表达。结果与正常对照组相比,槲皮素对照组各指标无明显改变,阿霉素组LDH活性增强,细胞存活率降低,Bcl-2表达减少,Bax表达增加,心肌细胞超微结构损伤明显,caspase-3 mRNA和蛋白的表达均升高;高中低剂量槲皮素均可减轻阿霉素所致的损伤。结论槲皮素对ADR致培养心肌细胞凋亡具有保护作用,其机制与调节细胞内凋亡相关蛋白caspase-3、Bcl-2和Bax的表达有关。