回医扎里奴思方对痰热腑实证脑缺血再灌注大鼠肿瘤坏死因子-α和内皮素-1表达的影响

目的探讨扎里奴思方对痰热腑实证脑缺血再灌注大鼠脑内肿瘤坏死因子(TNF)-α和内皮素(ET)-1表达的影响。方法将60只雄性SD大鼠随机分为假手术组、模型组、尼莫地平组、扎里奴思方组,每组15只。除假手术组外,其余各组均给予高脂喂养4 w后,再给予10%的自体粪便1 ml/100 g灌胃,1次/d,连续3 d,造成痰热腑实证模型;再采用线栓法制备大鼠大脑中动脉阻塞(MCAO)。大鼠给药剂量为尼莫地平组10.8 mg/kg、扎里奴思方组1.54 g/0.1 kg,制备MCAO模型前3 d灌胃给药。大鼠分别于缺血再灌注后1、3、7 d取脑;取材前进行脑组织含水量测定,采用免疫组化法检测脑缺血侧海马区TNF-α、ET-1表达,RT-PCR检测TNF-α mRNA和ET-1 mRNA的表达。结果与假手术组比较,模型组脑组织含水量增高(P<0.01)、TNF-α、ET-1阳性细胞和TNF-α mRNA、ET-1 mRNA表达明显增高(P<0.01);与模型组比较,尼莫地平组和扎里奴思方组脑组织含水量降低、TNF-α、ET-1阳性细胞数减少,TNF-α mRNA、ET-1 mRNA表达降低(P<0.01)。与尼莫地平组比较,扎里奴思方7 d组脑组织含水量降低、TNF-α、ET-1阳性细胞数减少和TNF-α mRNA、ET-1 mRNA表达降低(P<0.05)。结论扎里奴思方对痰热腑实证脑缺血再灌注大鼠脑神经元起保护作用,其机制可能与抑制大鼠脑内TNF-α和ET-1的表达有关。     

依达拉奉对脑缺血再灌注大鼠血管细胞黏附分子1的影响

目的探讨依达拉奉对脑缺血再灌注大鼠脑组织和血清血管细胞黏附分子1(VCAM-1)和细胞间黏附分子1(ICAM-1)水平的影响。方法将30只雄性SD小鼠随机分为假手术组、缺血再灌注组和依达拉奉组,每组10只。建立大鼠大脑中动脉缺血再灌注模型,24h后采集脑组织和血清,分别采用免疫组织化学、ELISA法检测VCAM-1和ICAM-1水平。结果与假手术组比较,缺血再灌注组大鼠脑组织和血清ICAM-1、VCAM-1明显升高(P<0.05);与缺血再灌注组比较,依达拉奉组脑组织ICAM-1、VCAM-1[(0.14±0.02)μg/L vs(0.19±0.04)μg/L、(0.12±0.02)μg/L vs(0.17±0.03)μg/L,P<0.05]和血清ICAM-1、VCAM-1[(1.03±0.29)μg/L vs(1.29±0.44)μg/L、(170.79±43.42)μg/L vs(261.85±73.05)μg/L,P<0.05]明显降低。结论依达拉奉能改善脑缺血再灌注大鼠的症状,其作用机制之一是抑制ICAM-1和VCAM-1的生成。     

回药扎里奴思方对大脑中动脉闭塞模型大鼠白细胞介素-6、-2含量的影响

目的探讨回药扎里奴思方对脑缺血急性期再灌注损伤后大鼠脑内白细胞介素(IL)-6和IL-2含量的影响。方法将SD大鼠随机分为假手术组、模型组、尼莫地平组、扎里奴思方组,除假手术组外其余各组均采用线栓法大脑中动脉闭塞(MCAO)复制脑缺血再灌注模型,用HE染色观察脑组织形态学改变,用酶联免疫吸附法(ELISA)及免疫组化法测定各组大鼠脑组织中IL-6和IL-2的表达,并对各组进行神经功能评分。结果假手术组脑内有少量IL-6和IL-2;脑缺血再灌注后IL-6和IL-2的表达开始上升,IL-6在3 d时达到高峰;与模型组比较,尼莫地平组与扎里奴思方组均能显著降低大鼠神经功能评分,改善再灌注损伤后大鼠脑组织病理形态,减少IL-6和IL-2的表达(P<0.05);在7 d时,扎里奴思方的作用较尼莫地平显著(P<0.05)。结论扎里奴思方可明显抑制大鼠急性期脑缺血再灌注损伤后脑组织中IL-6和IL-2的含量,且与用药时间呈正相关,这可能是其脑保护作用机制之一。     

回药扎里奴思方对痰热腑实脑缺血模型大鼠血脂、血浆同型半胱氨酸及内皮素-1的影响

目的探讨回药扎里奴思方对痰热腑实脑缺血急性期再灌注模型大鼠脂质代谢、血浆同型半胱氨酸(Hcy)及内皮素(ET)-1的影响。方法将SD大鼠随机分为正常组,假手术组,单纯脑梗死组,痰热腑实模型组,尼莫地平组,扎里奴思方组,采用10%的自体粪便灌胃加高脂饮食的方法复制痰热腑实动物模型,采用改良线栓法复制脑缺血再灌注(MCAO)模型。再灌注2 h后按相应分组灌胃给药,观察大鼠神经功能评分及行为学改变,心尖取血测其血清中总胆固醇(TC)、甘油三酯(TG)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)、Hcy含量,免疫组化法及酶联免疫标记法测定脑组织中ET-1的含量。结果与模型组比较,各用药组神经功能缺损及痰热腑实症状明显改善,血清中TC、TG、HDL-C、LDL-C、Hcy及ET-1含量显著降低。结论扎里奴思方可降低痰热腑实脑缺血再灌注模型大鼠急性期血脂及Hcy水平,减少ET-1的表达,具有保护脑神经细胞的作用,并对痰热腑实型脑缺血有明显的改善作用。     

扎里奴思方对局灶性脑缺血再灌注损伤大鼠P-糖蛋白的影响

目的比较缺血损伤不同时段大鼠血脑屏障P-糖蛋白(P-gp)时征表达及回药扎里奴思方对其表达的影响。方法 SD大鼠随机分为假手术组、模型组、尼莫地平组、扎里奴思方组,线栓法制备脑缺血再灌注模型,分别灌胃给药,于缺血再灌注后1、3、7、14 d取脑,检测大鼠脑皮质及海马区P-gp的表达。结果免疫组织化学染色结果显示,假手术组与模型组大鼠脑皮质及海马缺血区均可见P-gp阳性染色。与假手术组比较,不同再灌注时间模型组P-gp表达量均有显著性差异(P0.01),皮质及海马缺血区P-gp表达量均升高;与模型组比较,扎里奴思方组及尼莫地平组大鼠脑皮质及海马区P-gp表达量明显降低,尤以扎里奴思方3、14 d组为明显(P0.01)。结论扎里奴思方发挥抗脑缺血损伤、神经元保护作用机制可能是通过调节血脑屏障上P-gp的双向表达而实现的。     

心力衰竭患者血清胱抑素-C、血管细胞间黏附分子-1和细胞间黏附分子-1水平的表达及意义

目的观察心力衰竭患者血清胱抑素(Cys)-C、血管细胞间黏附分子(VCAM)-1、细胞间黏附分子(ICAM)-1的水平及意义。方法确诊为心力衰竭患者58例作为观察组,25例经体检证实为无明显器质性病变的成人血清标本作为对照组。检测两组血清中Cys-C、VCAM-1和ICAM-1的表达。结果观察组血清中Cys-C、VCAM-1和ICAM-1的表达明显高于对照组(均P<0.05),观察组血清中Cys-C、VCAM-1和ICAM-1的表达与心力衰竭的分级相关,相关性分析显示VCAM-1和ICAM-1呈正相关,其他指标间未见明显相关性。结论心力衰竭患者血清中Cys-C、VCAM-1和ICAM-1高表达对病变的发生和进展有一定的促进作用;VCAM-1和ICAM-1有协同作用。     

通心络超微粉对高脂饮食兔胸主动脉NF-κB、胞间黏附分子1及血管细胞黏附分子1表达的影响

目的探讨通心络超微粉对高脂饮食兔胸主动脉NF-κB、胞间黏附分子1（ICAM-1）及血管细胞黏附分子1（VCAM-1）表达的影响。方法健康雄性新西兰白兔32只,随机分为空白对照组、模型组、阿托伐他汀组、通心络组四组。空白对照组,饲以普通饲料;模型组,饲以高脂饲料;阿托伐他汀组,饲以高脂饲料同时阿托伐他汀（3mg·kg^-1·d^-1）灌胃;通心络组,饲以高脂饲料同时通心络超微粉（0．31g·kg^-1·d^-1）灌胃,连续给药,于6周末免疫组织化学染色法检测主动脉壁中NF-κB核转位情况、ICAM-1及VCAM-1蛋白表达情况,RT—PCR法检测ICAM-1 mRNA及VCAM-1 mRNA表达。结果与空白对照组相比,模型组家兔主动脉壁中NF—KB核转位明显增加。ICAM-1、VCAM-1基因及蛋白表达明显增多（P〈O．01）。与模型组相比,通心络组与阿托伐他汀组家兔主动脉壁中NF-κB核转位明显减少、ICAM-1、VCAM-1基因及蛋白表达明显减少（P〈0．01或P〈0．05）,通心络组显著少于阿托伐他汀组（P〈0．01）。结论通心络超微粉通过抑制NF-κB核转位进而降低ICAM-1、VCAM-1基因及蛋白表达,减轻动脉粥样硬化病理改变。     

环磷酰胺对大鼠脑出血血肿周围组织核因子-κB及细胞间黏附分子1表达的影响

目的研究环磷酰胺对大鼠脑出血血肿周围组织NF-κB和细胞间黏附分子1(ICAM-1)表达的影响。方法健康SD大鼠125只,随机分为假手术组(25只)、治疗组(50只)和对照组(50只),采用Fredrik建立的自体股动脉取血,并向大鼠尾壳核注射方法复制脑出血模型。各组按术后6、24、48、72 h及5 d分为5个时间点,经尾壳核行冠状切片,分别按干湿重法测脑含水量,免疫组织化学法测定血肿周围组织NF-κB及ICAM-1的表达。结果假手术组各时间点NF-κB、ICAM-1表达无明显变化。除6 h及5 d,治疗组24、48、72 h血肿周围脑组织含水量及NF-κB、ICAM-1表达均明显低于对照组(P0.05)。NF-κB表达与ICAM-1表达呈现同步性,而且NF-κB的表达高峰时间先于ICAM-1的表达。结论环磷酰胺能够减少并抑制NF-κB的表达,减轻脑出血血肿周围组织的炎性反应,起到神经保护作用。     

脑梗死急性期患者血清可溶性细胞间黏附分子-1、可溶性血管细胞黏附分子-1的表达

目的观察脑梗死急性期患者血清中可溶性细胞间黏附分子(s ICAM)-1和可溶性血管细胞黏附分子(s VCAM)-1的表达,分析其临床意义。方法 58例脑梗死急性期患者作为观察组,经体检证实无明显器质性病变的成年人血清标本28例作为对照组,应用酶联免疫吸附实验检测二组血清中s ICAM-1和s VCAM-1的表达。结果二组中s ICAM-1和s VCAM-1的表达差别显著。观察组s ICAM-1和s VCAM-1的表达与病变程度密切相关,而与性别及年龄无明显相关性。结论脑梗死急性期患者血清中s ICAM-1和s VCAM-1高表达,二者的上调参与病变形成和进展。     

脑缺血大鼠干扰素γ与细胞间黏附分子-1表达相关性研究

目的研究脑缺血时干扰素γ与细胞间黏附分子(ICAM)-1的表达是否具有相关性.方法将雄性SD大鼠54只随机分成6组(A、B、C、D、E、F组),每组9只.再将每组大鼠随机分成实验组(6只)和对照组(3只).A、B、C、D、E、F实验组用埋线法制造大鼠局灶性脑缺血-再灌注模型,分别于再灌注后1、3、6、9、12、24 h处死大鼠,取大鼠脑组织,应用免疫组织化学方法分别检测干扰素γ及ICAM-1的表达.高倍显微镜下计数10个不同视野阳性细胞的平均值.结果大鼠脑缺血-再灌注1、3、6、9、12、24 h时,干扰素γ及ICAM-1的表达逐渐增高,其中干扰素γ阳性的细胞是圆形、以细胞核为主的淋巴细胞,1 h阳性细胞表达数为3.2±1.3;6 h为7.0±2.2;24h为14.8±1.8.ICAM-1阳性细胞是扁平的血管内皮细胞,1 h的表达数为12.1±2.1;6 h为19.3±3.2;24 h为27.6±2.8.结论脑缺血时干扰素γ、ICAM-1的表达随时间延长动态地增高,两者具有相关性.干扰素γ也可能是脑缺血时ICAM-1表达上调的前炎性细胞因子.     

Cytochrome 1A1 and 1B1 gene diversity in the Zanzibar islands

Amodiaquine (AQ) is a 4‐aminoquinoline widely used in the treatment of malaria as part of the artemisinin combination therapy (ACT). AQ is metabolised towards its main metabolite desethylamodiaquine mainly by cytochrome P450 2C8 (CYP2C8). CYP1A1 and CYP1B1 play a minor role in the metabolism but they seem to be significantly involved in the formation of the short‐lived quinine‐imine. To complete the genetic variation picture of the main genes involved in AQ metabolism in the Zanzibar population, previously characterised for CYP2C8, we analysed in this study CYP1A1 and CYP1B1 main genetic polymorphisms. The results obtained show a low frequency of the CYP1A1*2B/C allele (2.4%) and a high frequency of CYP1B1*6 (approximately 42%) followed by CYP1B1*2 (approximately 27%) in Zanzibar islands. Genotype data for CYP1A1 and CYP1B1 show a low incidence of fast metabolisers, revealing a relatively safe genetic background in Zanzibar’s population regarding the appearance of adverse effects.     

Polymorphisms of the glutathione S-transferases mu-1 (GSTM1) and theta-1 (GSTT1) and the risk of advanced alcoholic liver disease

OBJECTIVE: The aim of this study was to determine whether null genotypes for glutathione transferase mu-1 (GSTM1) and theta-1 (GSTT1) influence the risk of development of advanced alcoholic liver disease. MATERIAL AND METHODS: GSTM1 and GSTT1 genotypes were identified on DNA through multiple analysis with polymerase chain reaction in 153 subjects diagnosed with advanced alcoholic liver disease and in 241 healthy controls. RESULTS: The frequency of the GSTM1 null genotype was not different between patients and controls (36.6% versus 41.1%, non-significant). The GSTT1 null genotype was more frequently found in patients than in controls (32% versus 22%, odds ratio 1.67, 95% CI 1.03-2.71, p =0.027). Moreover, patients were more likely to be simultaneous carriers of both GSTM1 and GSTT1 null genotypes (odds ratio 4.30, 95% CI 1.89-9.97, p =0.0003). CONCLUSIONS: The GSTT1 null genotype is more frequent among patients with advanced alcoholic liver disease than in controls. The coincidence of this genotype with the GSTM1 null genotype is four times more likely in patients. We suggest that polymorphisms affecting the activity of the glutathione S-transferase isoforms M1 and T1 may be associated with the risk of developing chronic severe ethanol liver damage.     

Polymorphisms of the glutathione S-transferases mu-1 (GSTM1) and theta-1 (GSTT1) and the risk of advanced alcoholic liver disease

Objective. The aim of this study was to determine whether null genotypes for glutathione transferase mu-1 (GSTM1) and theta-1 (GSTT1) influence the risk of development of advanced alcoholic liver disease. Material and methods. GSTM1 and GSTT1 genotypes were identified on DNA through multiple analysis with polymerase chain reaction in 153 subjects diagnosed with advanced alcoholic liver disease and in 241 healthy controls. Results. The frequency of the GSTM1 null genotype was not different between patients and controls (36.6% versus 41.1%, non-significant). The GSTT1 null genotype was more frequently found in patients than in controls (32% versus 22%, odds ratio 1.67, 95% CI 1.03–2.71, p=0.027). Moreover, patients were more likely to be simultaneous carriers of both GSTM1 and GSTT1 null genotypes (odds ratio 4.30, 95% CI 1.89–9.97, p=0.0003). Conclusions. The GSTT1 null genotype is more frequent among patients with advanced alcoholic liver disease than in controls. The coincidence of this genotype with the GSTM1 null genotype is four times more likely in patients. We suggest that polymorphisms affecting the activity of the glutathione S-transferase isoforms M1 and T1 may be associated with the risk of developing chronic severe ethanol liver damage.     

糖尿病肾病与MCP-1、SICAM-1的相关性及辛伐他汀对其干预治疗的作用

目的 探讨糖尿病肾病(DN)与血清单核细胞趋化蛋白1(MCP-1)、可溶性细胞问黏附分子1(sI-CAM-1)的相关性,以及辛伐他汀干预治疗对早期DN的作用.方法将60例DN患者随机分为对照组和辛伐他汀治疗组,治疗16周后,观察两组血清MCP-1、sICAM-1及尿白蛋白排泄率(UAER)变化,评价辛伐他汀对患者肾脏的保护作用.结果 与对照组比较,治疗组血清MCP-1、sICAM-1及UAER均明显降低(P均<0.05).结论 辛伐他汀对早期DN患者有肾脏保护作用,能延缓其进展为终末期肾病.     

血管生成素1和血栓调节蛋白1在STZ鼠肾脏中的表达及其意义

目的：探讨血管生成素1（angiopoietin-1,Ang-1）和血栓调节蛋白1（thrombomodulin-1,TM-1）在糖尿病鼠肾脏中的表达变化及其与肾脏微血管病变的关系. 方法：STZ诱导的糖尿病大鼠肾病模型,设正常对照和模型组,于2、4、8、12、16、20、24周,采用免疫组化观察肾脏Ang-1和TM-1表达变化以及RT-PCR观察肾脏Ang-1mRNA表达,并行相关性分析. 结果：糖尿病组4和8周时肾脏Ang-1mRNA表达显著上调, 24周时明显低于对照组;糖尿病组4～24周免疫组化显示肾小球Ang-1着染均显著高于对照组,峰值在4～8周,12周后逐渐下调;糖尿病组2～20周肾小球TM-1明显增强;Ang-1和TM-1呈正相关. 结论：糖尿病肾脏存在Ang-1和TM-1的异常改变,表现为早中期表达上调,后期表达下调,并且这种改变可能与糖尿病肾脏新生血管的生成有关.     

Concerning the significance of paraoxonase-1 and SR-B1 genes in atherosclerosis

High-density lipoprotein (HDL) is an independent protective factor against cardiovascular disease. The enzyme paraoxonase-1 (PON-1) contributes to the anti-atherogenic effects of HDL. In vitro studies have demonstrated that paraoxonase's substrates are highly heterogeneous and that some contribute to the development of atherosclerotic lesions. The atheroprotective role of PON-1 was established in genetically engineered animal models. In humans, the PON-1 Gln192Arg and Met55Leu polymorphisms appear to be associated with increased susceptibility to cardiovascular disease and with different PON-1 activity levels and concentrations. The CLA-1 (CD36 and Lysosomal integral membrane protein-II Analogous-1) gene is the human homologue of the murine SR-B1 (Scavenger Receptor class B type 1) gene. SR-B1 was the first high-affinity HDL receptor to be identified at the molecular level. The CLA-1 receptor plays a pivotal role in HDL-mediated reverse cholesterol transport by mediating the selective uptake of free cholesterol as well as of native and oxidized cholesteryl esters. Its atheroprotective role has also been established in transgenic mice studies. Several polymorphic variants of the CLA-1 gene have been described, some of which are associated with phenotypic changes in plasma lipoproteins. Both genes participate in the complex HDL metabolic pathway and, presumably, also in defense mechanisms against oxidative stress.