右美托咪定对大鼠离体肺缺血再灌注所致线粒体损伤的影响

目的：探究右美托咪定（dexmedetomidine,Dex）对大鼠离体肺缺血再灌注所致线粒体损伤的影响。方法：将SD大鼠随机分成4组（n=6）：对照组（C组）、缺血再灌注组（IR组）、1 nmol/L Dex组（D1组）、10 nmol/L Dex组（D10组）,制备大鼠离体肺缺血再灌注模型。记录平衡末（T0）、再灌注即刻（T1）、再灌注30 min（T2）和再灌注60 min（T3）时的潮气量（tidal volume,VT）、肺顺应性（compliance,Cdyn）、气道阻力（airway resistance,Raw）和肺静脉氧分压（oxygen partial,PaO2）;测定肺湿/干重比;HE染色观察组织病理学改变;测定灌流末流出液乳酸脱氢酶（LDH）活性和肺组织中活性氧（ROS）、丙二醛（MDA）、三磷酸腺苷（ATP）含量以及超氧化物歧化酶（SOD）活性。分离肺组织线粒体,检测线粒体肿胀程度和线粒体膜电位（MMP）。结果：与C组相比,IR组、D1组、D10组肺功能不同程度降低,LDH活性升高,ROS、MDA增加,SOD活性下降,ATP生成减少,线粒体肿胀程度升高,MMP下降（P < 0.05）;与IR组相比,D1组、D10组肺功能改善,病理显示肺损伤明显减轻,LDH释放减少,ROS、MDA含量减少,SOD活性升高,ATP生成增加,线粒体肿胀程度减轻,MMP上升（P < 0.05）;与D1组相比,D10组改善肺功能作用更明显,Raw下降,LDH活性降低,SOD活性升高,线粒体肿胀程度减轻（P < 0.05）。结论：右美托咪定减轻了离体肺缺血再灌注损伤,其机制可能与减轻线粒体损伤,减少氧化应激反应有关。     

阿托伐他汀钙对缺血再灌注损伤内皮细胞的保护作用及对氧化应激的影响

目的探讨阿托伐他汀钙对缺血再灌注诱导人脐静脉内皮细胞(HUVEC)损伤的保护作用及对氧化应激的影响。方法体外培养HUVEC,分为空白对照组、缺氧模型组、阿托伐他汀钙高剂量组、阿托伐他汀钙低剂量组,每组重复10个复孔。缺氧培养制作模拟缺血再灌注细胞模型。采用四甲基偶氮唑盐比色法(MTT法)检测HUVEC增殖活力,检测上清液中乳酸脱氢酶(LDH)活力分析细胞的损伤程度,检测上清液丙二醛(MDA)水平、超氧化物歧化酶(SOD)活性及总抗氧化能力(T-AOC)来分析各组HUVEC氧化应激状态。结果 (1)缺氧模型组光密度(OD)值低于空白对照组,差异有统计学意义(P<0.05);LDH外漏高于空白对照组,差异有统计学意义(P<0.05)。阿托伐他汀钙高、低剂量组OD值高于缺氧模型组,差异有统计学意义(均P<0.05),LDH外漏低于缺氧模型组,差异有统计学意义(均P<0.05)。(2)缺氧模型组MDA水平高于空白对照组,差异有统计学意义(P<0.05);SOD活性低于空白对照组,差异有统计学意义(P<0.05);T-AOC低于空白对照组,差异有统计学意义(P<0.05)。阿托伐他汀钙高、低剂量组MDA水平低于缺氧模型组,差异有统计学意义(均P<0.05);SOD活性高于缺氧模型组,差异有统计学意义(均P<0.05);T-AOC高于缺氧模型组,差异有统计学意义(均P<0.05)。结论阿托伐他汀钙可改善缺血再灌注损伤细胞的增殖活力,减轻细胞的损伤程度,降低氧自由基的损伤,提高抗氧化能力。     

后循环TIA与椎基底动脉血管形态特点研究

目的探讨以头晕眩晕为主要表现的后循环短暂性脑缺血发作(PCI-TIA)患者的椎基底动脉特点。方法 2012-02—2013-01收集符合条件病人资料115例,依据椎动脉优势及基底动脉形态特点进行分组讨论,比较各组性别、年龄、动脉硬化、血脂、合并糖尿病、高血压、高尿酸(UA)血症、高同型半胱氨酸(Hcy)血症情况,分析PCI-TIA发病特点。结果 (1)左侧椎动脉优势占47.0%,右侧优势16.5%,无明显优势现象36.5%。(2)优势组平均LDL、合并动脉硬化、高血压情况高于对照组,差异有统计学意义(P<0.05)。(3)性别、Hcy、UA、合并糖尿病方面椎动脉分组无明显差异。(4)基底动脉形态C型占29.6%,反C型15.7%,S型13.9%,其他形态41.8%。(5)S型Hcy平均水平较高,且与反C型、对照组比较差异具有统计学意义(P<0.05)。C型、反C型、S型合并动脉硬化、高血压的百分比高于对照组,差异具有统计学意义(P<0.05)。结论椎动脉优势和基底动脉迂曲导致后循环TIA(PCI-TIA)发病年龄提前,与动脉硬化、高血压、血管内膜的损害存在关系。     

Ischemic stroke susceptibility gene in a Northern Han Chinese population

Interleukin-18 gene promoter polymorphisms are potential risk factors for ischemic cerebrovascular disease, and the –607C allele may increase ischemic stroke risk in the Han Chinese population. In the present study, we recruited 291 patients with ischemic cerebrovascular disease from the Affiliated Hospital of Qingdao University Medical College, China, and 226 healthy controls. Both patients and controls were from the Han population in northern China. Immunoresonance scattering assays detected increased serum amyloid A protein, C-reactive protein, and interleukin-18 levels in ischemic cerebrovascular disease patients compared with healthy controls. Analysis of the –607C/A （rs1946518） polymorphism in the interleukin-18 gene promoter showed ischemic cerebrovascular disease patients exhibited increased frequencies of the CC genotype and C alleles than healthy controls. Genotype and allele frequencies of the interleukin-18 –137G/C （rs187238） polymorphism and the –13T/C （rs11024595） polymorphism in the 5＇-flanking region of serum amyloid A, showed no significant difference between the two groups. Multivariate logistic regression analysis on the interleukin-18 promoter A/C genetic locus, for correction of age, gender, history of smoking, hypertension, diabetes mellitus, hypercholesteremia, and an ischemic stroke family history, showed ischemic cerebrovascular disease risk in individuals without the A allele （C homozygotes） was 2.2-fold greater than in A allele carriers. Overall, our findings suggest that the –13T/C （rs11024595） polymorphism in the 5′-flanking region of serum amyloid A has no correlation with ischemic cerebrovascular disease, but the C allele of the –607C/A （rs1946518） polymorphism in the interleukin-18 promoter is a high-risk factor for ischemic cerebrovascular disease in the Han population of northern China. In addition, the A allele is likely a protective gene for ischemic cerebrovascular disease.     

Pretreatment with scutellaria baicalensis stem-leaf total flavonoid prevents cerebral ischemia- reperfusion injury

Pretreatment with scutellaria baicalensis stem-leaf total flavonoid has protective effects against ischemia and attenuates myocardial ischemia-reperfusion injury. In this study, rats were given scutellaria baicalensis stem-leaf total flavonoid intragastrically at 50, 100, and 200 mg/kg per day for 7 days before focal cerebral ischemia-reperfusion injury models were established using the suture method. We then determined the protective effects of scutellaria baicalensis stem-leaf total flavon- oid pretreatment on focal cerebral ischemia-reperfusion injury. Results showed that neurological deficit scores increased, infarct volumes enlarged, apoptosis increased and Bcl-2 and Bax protein expression were upregulated at 24 hours after reperfusion. Pretreatment with scutellaria baicalensis stem-leaf total flavonoid at any dose lowered the neurological deficit scores, reduced the infarct volume, prevented apoptosis in hippocampal cells, attenuated neuronal and blood-brain barrier damage and upregulated Bcl-2 protein expression but inhibited Bax protein expression. Doses of 100 and 200 mg/kg were the most efficacious. Our findings indicate that pretreatment with scutel- laria baicalensis stem-leaf total flavonoid at 100 and 200 mg/kg can improve the neurological func- tions and have preventive and protective roles after focal cerebral ischemia-reperfusion injury.     

缺血再灌注损伤与细胞信号转导

短暂的缺血会对器官造成损伤,但是在恢复灌注后,损伤反而进一步加剧,这种现象称为缺血再灌注损伤(ischemia reperfusion injury,IRI).临床上涉及缺氧/复氧过程的手术都不可避免地会发生IRI,比如重大器官的移植、冠脉搭桥、溶栓术等.IRI一直是医学研究的热点,近年来研究发现,缺血再灌注(ischemia reperfusion,IR)时,钙超载、供能不足和氧自由基的大量产生等理化因素刺激细胞,诱发信号介导的细胞损伤、凋亡是造成IRI的一个重要原因.本文就IRI与信号通路的研究进展做简要综述.     

异氟醚和卡托普利联合预处理对兔心肌缺血再灌注心肌酶学的影响

目的通过心肌酶学等检测指标评估异氟醚、卡托普利联合预处理对缺血再灌注的心肌保护作用。方法新西兰大白兔48只随机分成6组(n=8),假手术组(S组)仅开胸分离冠状动脉左前降支;缺血组(I/R组):缺血30 min后再灌注120min;缺血预处理组(IPC组):缺血5 min、再灌注5 min循环3次后处理同缺血组;异氟醚组(I组):给予1.1%异氟醚吸入30 min洗脱15 min后处理同I/R组;卡托普利组(C组)24 h给予卡托普利片25 mg/kg后处理同I/R组;联合预处理组(I+C组)24 h给予卡托普利片25 mg/kg后处理同I组。各实验组分别检测不同时点的心肌酶和心肌肌钙蛋白I(cTnI)的变化,在再灌注结束即刻取血检测丙二醛(MDA)浓度及超氧化物歧化酶(SOD)活性。结果各处理组心肌酶学指标均高于S组(P<0.05或P<0.01),但增高程度低于I/R组(P<0.05),IPC组和I+C组又较I组和C组低(P<0.05)。各组MDA均增高,SOD降低(P<0.01),但与I/R组比,各药物处理组MDA降低,SOD较高(P<0.01)。IPC组和I+C组MDA和SOD分别较I组和C组降低和升高(P<0.05)。结论异氟醚、卡托普利联合预处理明显减轻兔心肌缺血再灌注心肌酶学改变,较单独应用异氟醚、卡托普利预处理的心肌保护作用增强,其效果与缺血预处理相似。