阿托发他汀对糖尿病大鼠外周血和肾组织核因子κB的影响

目的 探讨阿托伐他汀对链脲佐菌素诱导的糖尿病大鼠肾组织与外周血单个核细胞(PBMC)中核因子κB(NF-κB)活性的影响.方法 30只雄性SD大鼠分成对照组、糖尿病组和阿托伐他汀治疗组;酶联免疫吸附法(ELISA)测定各组大鼠PBMC中NF κB活性;免疫组化检测各组大鼠肾组织NF-κB、单核细胞趋化蛋白1(MCP-1).结果 糖尿病大鼠PBMC和肾小球中NF κB显著高于对照组(P＜0.01).与糖尿病大鼠相比,阿托伐他汀明显抑制NF-κB活化及MCP-1和纤黏连蛋白(FN)表达(P＜0.05),减少24 h尿蛋白排泄,改善肾功能及肾病理学损害.结论 NF-κB在糖尿病肾病发病中具有重要作用,抑制NF-κB的活化可能是他汀类药物发挥肾脏保护作用的机制之一.     

单核细胞株THP-1分化为泡沫细胞过程中清道夫受体A变化及阿托伐他汀的干预作用

目的 研究单核细胞株THP-1分化为巨噬细胞、泡沫细胞过程中细胞清道夫受体A（SRA）表达、单核细胞趋化蛋白-1（MCP-1）分泌及应用阿托伐他汀干预的情况。方法 佛波醇酯诱导THP-1细胞分化为巨噬细胞,将其分为对照组、OX-LDL组（泡沫细胞组）、OX-LDL＋阿托伐他汀组（再分为低、中、高浓度3组）。用ELISA法,测定细胞培养液中MCP-1浓度。将SRA特异性结合配体DiI-Ac-LDL与细胞孵育,应用荧光显微镜观察各组细胞SRA蛋白表达及活性情况。并将MCP-1浓度与SRA蛋白活性进行相关性分析。结果400倍光镜下观察到细胞株THP-1在佛波醇酯诱导下转变为泡沫细胞。与对照组相比,OX-LDL组MCP-1表达升高,6h后升高明显（P〈0．05）,12h达高峰（P〈0．01）,24h后逐渐下降（P〈0．01）。阿托伐他汀药物干预,呈剂量依赖性降低MCP．1水平。OX-LDL组SRA蛋白活性水平明显高于对照组（P〈0．01）。阿托伐他汀干预,呈剂量依赖性下调SRA蛋白活性水平。各组细胞12hMCP．1浓度与SRA蛋白活性水平呈明显正相关（r=0．683,P〈0．01）。结论SRA、炎症因子MCP-1在THP-1细胞分化为泡沫细胞过程中发挥重要作用,阿托伐他汀抑制MCP-1与SRA表达,可能是其抗动脉粥样硬化形成的重要机制。     

氟伐他汀对高糖环境中肾小球系膜细胞胞外信号调节激酶活性的影响

高糖环境中SD大鼠肾小球系膜细胞胞外信号调节激酶（ERK）活性、转化生长因子β1（TGF—β1）mRNA水平升高，Ⅳ型胶原含量增多，氟伐他汀可抑制上述反应，提示ERK通路的激活参与糖尿病肾病的发生、发展，氟伐他汀可能通过抑制ERK通路活化及TGF—β1表达发挥非降脂相关的肾保护作用。     

阿托伐他汀通过PPARβ／δ信号通路下调衰老心肌TNF-α表达的研究

目的：观察阿托伐他汀下调老年大鼠心肌肿瘤坏死因子-α（TNF-α）表达的作用及其与过氧化物酶体增殖物激活型受体β／δ（PPARβ／δ）信号通路之间的关系。方法：分离培养24个月龄大鼠的心肌细胞,将心肌细胞分为空白对照组、溶剂对照组、阿托伐他汀组、阿托伐他汀＋PPARβ／δ拮抗剂GSK0660组。各组细胞分别加入细胞培养液、二甲基亚砜（DMSO）、阿托伐他汀、阿托伐他汀＋GSK0660处理。用RT—PCR方法检测各组大鼠衰老心肌细胞的TNF-αmRNA表达水平,用westernblot方法检测各组TNF-α蛋白含量。结果：（1）与空白对照组相比,溶剂对照组大鼠衰老心肌细胞的TNF-α mRNA和蛋白水平均无显著差异;（2）与空白对照组相比,阿托伐他汀组的TNF-α mRNA和蛋白水平含量均显著降低（P〈0．01）;（3）阿托伐他汀＋GSK0660组的TNF-α mRNA表达水平及蛋白含量均显著高于阿托伐他汀组,但仍低于空白对照组（P〈0．05）。结论：阿托伐他汀可通过激活PPARβ／δ信号通路下调衰老心肌细胞TNF—d的表达。     

阿托伐他汀对脂多糖刺激下PBMC分泌TNF-α、IL-1β的影响

目的观察阿托伐他汀对脂多糖（LPS）刺激下外周血单核细胞（PBMC）分泌TNF-α、IL-1β的影响。方法Ficoll密度梯度离心法分离健康人外周血单个核细胞,不同浓度阿托伐他汀预处理2h,而后加入10ng/ml LPS共同培养24h,采用酶联免疫吸附测定法（ELISA）检测单核细胞培养上清液肿瘤坏死因子-α（TNF-α）、白细胞介素-1β（IL-1β）的水平。结果1μmoL／L阿托伐他汀减少LPS刺激下PBMC分泌TNF-α 53．3％、IL-1β 35．4％,10μmoL／L阿托伐他汀减少TNF-α 82．0％、IL-1β 65．6％。结论阿托伐他汀能有效抑制LPS刺激下PBMC TNF-α及IL-1β的分泌。     

阻断PPARβ/δ途径对阿托伐他汀抑制衰老心肌细胞中MMP-9表达的影响

目的：观察阻断过氧化物酶增殖物激活型受体β/δ（peroxisome proliferator activated receptor β/δ,PPARβ/δ）信号通路对阿托伐他汀抑制老年大鼠心肌细胞基质金属蛋白酶 9（matrix metalloproteinase-9,MMP-9）表达的影响。方法：分离培养24个月龄大鼠的心肌细胞,将培养的心肌细胞分为空白对照组、溶剂对照组、阿托伐他汀组及PPARβ/δ拮抗剂GSK0660＋阿托伐他汀组,4组细胞依次分别加入细胞培养液、二甲基亚砜（dimethyl sulfoxide,DMSO）、阿托伐他汀及阿托伐他汀＋GSK0660处理。用RT-PCR方法检测各组大鼠心肌细胞中MMP-9 mRNA表达水平,用Western blot方法检测各组大鼠心肌细胞的MMP-9蛋白的含量。结果：①与空白对照组相比,溶剂对照组大鼠心肌细胞中MMP-9 mRNA表达水平和其蛋白含量均无显著差异,阿托伐他汀组心肌细胞中MMP-9 mRNA表达水平和其蛋白含量均显著降低（P〈0.01）;②GSK0660＋阿托伐他汀组心肌细胞中MMP-9 mRNA表达水平及其蛋白含量均显著高于阿托伐他汀组（P〈0.05或P〈0.01）,但仍低于空白对照组（P〈0.05）。结论：阿托伐他汀可激活PPARβ/δ信号通路下调衰老心肌细胞中MMP 9的表达。     

贝那普利联合前列腺素E1和阿托伐他汀治疗早期糖尿病肾病的临床观察

糖尿病早期肾病患者40例,随机分成（每组20例）：贝那普利联合前列腺素E1组,贝那普利联合阿托伐他汀组。观察治疗3周。结果两组均能减少UAER（P均〈0．05）,但贝那普利联合前列腺素E1组降低UAER更明显。TG和Tch均有不同程度的降低,但贝那普利联合阿托伐他汀组更明显（P〈0．05）。结论贝那普利联合前列腺素E1治疗早期糖尿病肾病能更有效地降低UAER;贝那普利联合阿托伐他汀则降低Tch、TG更明显,提示临床治疗早期糖尿病肾病时,可将贝那普利、前列腺素E1和阿托伐他汀三药联合应用。     

大黄素对急性胰腺炎大鼠胰腺核因子-kB活化的影响

目的观察大黄素对急性胰腺炎(AP)大鼠胰腺组织核因子-kB(NF-kB)活化的影响,初步阐明大黄素治疗 AP 的分子作用机制。方法雄性 SD 大鼠采用持续输注雨蛙素(5 μg·kg~(-1)·h~(-1))法建立急性水肿性胰腺炎模型,分为注射后5、30min 及1、2、4、6 h 组,停止输注后6h 组;造模前2h 大鼠腹腔注射大黄素(10、30、100mg/kg)组及生理盐水对照组。采用电泳迁移率改变分析实验检测 NF-kB DNA 结合活性,Western blot 检测 NF-kB 抑制蛋白(ⅠkBs)的ⅠkBα和ⅠkBβ降解水平,Northern blot 检测 NF-kB 信号下游效应分子单核细胞趋化蛋白-1(MCP-1)和细胞间粘附分子-1(ICAM-1)基因表达。结果超生理剂量的雨蛙素可诱导大鼠胰腺 NF-kB 发生双相活化,活化高峰出现在雨蛙素注射30min 和4h 后,其相对面积灰度值分别为正常对照的(3.9±2.0)和(7.7±3.2)倍(n=4,P 值均<0.01)。大黄素10、30和100mg/kg剂量治疗组大鼠胰腺 NF-kB 活性较 AP 模型组分别下降45%,62%和84%(30min)和28%,74%和80%(4h,n=4,P 值均<0.01)。同时,大黄素(100mg/kg)可明显抑制雨蛙素诱导的胰腺ⅠkBα和ⅠkBβ蛋白降解(n=4,P 值均<0.01)。与其对 NF-kB 活化的抑制作用一致,大黄素剂量依赖性地抑制雨蛙素诱导的胰腺 MCP-1和 ICAM-1基因表达。结论大黄素可抑制胰腺内ⅠkBs/NF-kB 信号转导通路活化,从而抑制炎性细胞因子和粘附分子基因表达,发挥其对 AP 的治疗作用。     

阿托伐他汀对脑梗死患者血小板GMP140、CD62P和CD63水平的影响

目的：观察阿托伐他汀对急性脑梗死患者血浆血小板仅颗粒膜蛋白（GMP-140）、P-选择素（CD62p）和溶酶体膜蛋白（CD63）水平的影响，探讨阿托伐他汀对脑梗死患者血小板活化功能的抑制作用。方法：120例急性脑梗死患者随机分为阿托伐他汀组和常规治疗组，以60例健康体检者作为正常对照组，采用双抗体夹心酶联免疫吸附法和流式细胞术分别测定治疗前和治疗4周时血浆GMP-140、CD62p和CD63水平，并应用美国国立卫生院卒中量表评分（NIHSS）标准对治疗前后进行评分。结果：急性脑梗死患者血浆GMP140、CD62p和CD63水平显著高于正常对照组（P〈0．001），且NIHSS评分与GPM-140、CD62p和CD63水平呈线性相关（r分别为0．899、0．887和0．823，P均〈0．01）。阿托伐他汀组治疗后血浆GMP-140、CD62p和CD63水平均较治疗前显著下降（P〈0．05），而常规治疗组治疗前后无明显变化。阿托伐他汀组和常规治疗组NIHSS评分明显高于治疗前（P〈0．05），且阿托伐他汀组显著优于常规治疗组（P〈0．05）。结论：阿托伐他汀能降低急性脑梗死患者血浆GMP-140、CD62p和CD63水平，具有抑制血小板活化和促进神经功能恢复的作用。     

阿托伐他汀治疗阿尔茨海默病机制探讨

目的探讨阿托伐他汀治疗阿尔茨海默病（AD）的机制。方法将50只大鼠随机分为5组,除对照组外均建立AD模型,阿托伐他汀低、中、高剂量组分别予阿托伐他汀5、10、20mg/kg药物水溶液灌胃,对照组、模型组给予等体积生理盐水灌胃,1次／d。10d后行5d水迷宫试验测试大鼠潜伏期,同时采用Western Blot法检测各组脑组织Caspase-12蛋白表达情况。结果与对照组比较,模型组潜伏期明显延长,脑组织中Caspase-12蛋白表达升高（P均〈0．05）;与模型组比较,阿托伐他汀低、中、高剂量组潜伏期明显缩短,脑组织中Caspase-12蛋白表达降低,中高剂量组更明显（P均〈0．05）。结论阿托伐他汀可改善AD大鼠学习记忆能力,机制为降低Caspase-12表达。     

青少年高血压的研究进展

随着人们生活和行为方式的改变,高血压发病明显呈年轻化趋势。在青少年时期识别高血压病高危人群有助于早期进行有效干预和治疗,降低未来高血压的发生率及其严重性。现试从青少年高血压的诊断、发病因素、特点、治疗策略等方面的研究进展作一综述。     

Morbidity in cardiovascular diseases in immigrants in Sweden

INTRODUCTION: Although immigration to Sweden has increased in the last few decades, the incidence rates of cardiovascular disease and coronary heart disease in immigrants are unknown. The aim of the present study is to estimate whether place of birth affects the incidence rates of cardiovascular disease and coronary heart disease. MATERIAL AND METHODS: The study was designed as a follow-up study on morbidity in cardiovascular disease and coronary heart disease between 1 January 1997 and 31 December 1998, including three and a half million persons with age range 35-64 years, of whom 550 000 were born abroad, from the database MigMed consisting of the whole Swedish population. Incidence rates and relative risks were estimated by indirect standardization and a proportional hazard model. RESULTS: The age-adjusted risk of coronary heart disease was higher in most foreign-born groups than in Swedes. For example, in nine of 12 male groups, the relative risks varied between 1.1 and 2.2, and in seven of 12 female groups, the relative risks varied between 1.4 and 2.5. When also adjusting for level of education and employment status, the risks were still high, but on a lower level. CONCLUSIONS: Foreign-born people possess an over-risk of cardiovascular or coronary heart disease(CVD/CHD) compared with Swedish-born persons, also when level of education and employment status are taken into account.     

C·肉毒杀鼠素(冻干剂)应用研究

目的为研究C·肉毒杀鼠索对杀灭达乌尔黄鼠(简称黄鼠)的大面积应用情况和对家畜、家禽的毒害作用,进行了C·肉毒杀鼠素的应用研究.方法大面积投毒采用ES-2药饵撒播机[1],间隔约80m进行条投.羊、鸡采用直接灌胃.结果大面积应用的灭鼠率为83.72%.对羊、鸡最高剂量分别为500万MLD、150万MLD,均未出现中毒现象.结论 C·肉毒杀鼠素是较为理想的草原大面积杀灭黄鼠的理想、首选药物.     

高龄老年高血压的临床研究进展

随着社会老龄化进程的加快,80岁以上高龄老人的绝对数量以及占总人口的比例均在增加,如何提高高龄老年高血压的防治水平备受关注。现试从高龄老年高血压的临床特点、治疗策略等方面的临床研究进展作一综述。     

中国老年性耳聋的研究与干预进展

老年性耳聋已成为影响我国老年人生活质量的最主要的慢性病之一。助听器是目前帮助听力损失的老年人克服交流障碍的主要手段。在我国,数字助听器已逐渐取代模拟助听器并且体现出了更好的效果。但是老年听力损失患者中使用助听器的比例仍然很小。人工耳蜗植入也已被应用在老年患者中。我国针对老年人的听力康复服务还有较长的路要走。     

Sex Differences in Ethanol-induced Dopamine Release in Nucleus Accumbens and in Ethanol Consumption in Rats

In vivo microdialysis was used to examine changes in nucleus accumbens and striatal dopamine, dihydrophenylacetic acid (DO-PAC), and homovanillic acid (HVA) following acute administration of ethanol (0.0, 0.25, 0.5, 1.0, or 2.0 g/kg) in male and female Long-Evans rats. Following dialysis, rats were trained to bar-press for oral ethanol reinforcement. In nucleus accumbens, females showed significant increases in extracellular dopamine following 0.25 or 0.5 g/ kg ethanol, but did not show significant increases over baseline at the higher doses. Males showed slight increases in dopamine at the lower doses and decreased dopamine at 2.0 g/kg. In striatum, both sexes showed increased dopamine at the lower doses and decreased dopamine at 2.0 g/kg. There were slight increases in nucleus accumbens DOPAC and HVA at some doses in both sexes, but no changes in striatal metabolite levels. In addition to showing increased responsiveness to ethanol-induced mesolimbic dopamine stimulation, females consumed more ethanol than males during behavioral testing. The pattern of both greater ethanol-induced nucleus accumbens dopamine release and greater ethanol consumption in females supports the hypothesis that ethanol reward is mediated, at least in part, by the mesolimbic dopamine system.     

Epstein-Barr virus in malignancies in renal transplant recipients in Japan

A role for Epstein-Barr virus (EBV) in the development of malignancies including lymphomas, and carcinoma of the stomach, nasopharynx, thymus and salivary gland is suggested. It is indicated that EBV evokes polyclonal-B-cell-proliferative diseases in immunocompromised hosts, such as transplant patients, which results in monoclonal malignant lymphomas. The suppression of immune functions in these patients is thought to lead to incomplete elimination of the cells expressing EBV latent infection genes. To examine the etiological role of EBV in the development of malignancies following renal transplant in Japan, 42 malignancies in 1744 cases of renal transplant were studied for the presence and type of EBV. The polymerase chain reaction revealed that 5 malignancies were positive for EBV, all type A: 2 of 2 cases of non-Hodgkin's lymphoma (NHL), 2 of 8 cases of gastric adenocarcinoma of the common type, and 1 of 2 cases of gastric plasmacytoma. In situ hybridization revealed positive signals in the nucleus of tumor cells in 2 cases of NHL and 1 of plasmacytoma. Positive signals were found in the small lymphoid cells but not in the tumor cells in 2 cases of gastric carcinoma. On the basis of these findings, a role for EBV in the development of malignancies in renal transplant patients is unlikely except for lymphoid neoplasias.Abbreviations PCB polymerase chain reaction - EBV Epstein-Barr virus - NHL non-Hodgkin's lymphoma     

糖尿病大鼠心室肌细胞钾通道的改变

目的研究糖尿病大鼠心室肌细胞钾通道的改变及增加葡萄糖代谢对其的作用。方法取体重150～200g的雄性SpragueDawley大鼠,腹腔注射链脲菌素(STZ)建立糖尿病模型,采用酶解法获得单个心室肌细胞,应用膜片钳全细胞记录技术记录钾电流。结果糖尿病大鼠心室肌细胞瞬间外向性钾流(Ito)密度较对照组显著降低[ 60mV时,分别为(15.90±1.19)pA/pF(n=25)和(28.55±0.97)pA/pF(n=12),P<0.001];分别用100nmol/L胰岛素及1.5mmol/L二氯乙酸在体外预处理心室肌细胞4～5h和3～4h使Ito密度恢复至对照组水平[ 60mV时,分别为(29.40±0.38)pA/pF(n=20)和(27.35±0.97)pA/pF(n=12)]。结论糖尿病大鼠心室肌细胞钾通道功能发生改变,增加葡萄糖代谢可逆转这一改变,提示葡萄糖代谢与Ito功能间存在一定关系。