梓醇对衰老大鼠血管内皮细胞的保护作用研究

目的探讨梓醇对D-半乳糖诱导的衰老大鼠血管内皮细胞的保护作用及对内皮细胞凋亡率及凋亡相关基因Bcl-2、Bax、Caspase-3表达的影响。方法选取3月龄Wistar大鼠32只,随机抽取8只作为正常组,余24只腹腔注射D-半乳糖复制衰老模型。造模成功后随机分为模型组、低剂量组[梓醇5 mg/(kg·d)腹腔内注射]和高剂量组[梓醇10 mg/(kg·d)腹腔内注射]3组,每组8只。12周后处死大鼠。显微镜下观察大鼠主动脉血管内皮细胞的形态学改变; TUNEL法原位标记凋亡的血管内皮细胞,计算细胞凋亡率;免疫组化法检测大鼠主动脉血管内皮细胞Caspase-3蛋白的表达; RT-PCR法检测Bcl-2及Bax的表达,并计算Bcl-2/Bax的比值。结果 D-半乳糖所致衰老大鼠主动脉血管内皮细胞出现明显病理学改变,与模型组比较,梓醇低剂量组及高剂量组均能明显改善大鼠主动脉血管内皮细胞的病理损害。模型组主动脉血管内皮细胞凋亡率明显高于正常组(P 0.01),梓醇低剂量组与高剂量组细胞凋亡率均明显低于模型组(P 0.01)。模型组Bcl-2的表达量明显低于正常组(P 0.01),而高剂量组Bcl-2的表达量明显高于模型组;模型组Bax的表达量明显高于正常组(P 0.01),高剂量组明显低于模型组;模型组Bcl-2/Bax比值明显低于正常组,梓醇低剂量组与高剂量组均能明显提高Bcl-2/Bax比值,与模型组比较差异有统计学意义(P 0.05或P 0.01);模型组Caspase-3蛋白表达明显高于正常组,而低剂量组与高剂量组Caspase-3蛋白表达均明显低于模型组(P 0.01)。结论梓醇能保护D-半乳糖所致衰老大鼠主动脉血管内皮细胞的形态学损害。梓醇的抗衰老作用可能与梓醇能抑制主动脉内皮细胞促凋亡基因Bax及Caspase-3的表达,促进抗凋亡基因Bcl-2的表达,同时上调Bcl-2/Bax比值有关。提示梓醇能抑制D-半乳糖诱导的衰老大鼠的血管内皮细胞凋亡,从而起到保护血管内皮细胞、延缓衰老的作用。梓醇的抗血管衰老作用呈现一定的剂量依赖性。     

动脉粥样硬化对大鼠心肌钙敏感受体表达和细胞凋亡的影响

目的 观察高脂血症和动脉粥样硬化对大鼠心肌钙敏感受体(CaSR)表达和细胞凋亡的影响.方法 采用腹腔注射维生素(Vit)D3(6×105U/kg)+高脂饮食6周的方法,建立大鼠高脂血症和动脉粥样硬化模型.Wistar大鼠随机分为正常对照组(n=12)和动脉粥样硬化组(n=12).采用RT-PCR和Western blot分别观察CaSR、Bax、Bcl-2、easpase-3的mRNA和蛋白表达.TUNEL染色观察心肌细胞凋亡情况.光镜观察腹主动脉和心肌形态学变化.电镜观察心脏超微结构变化.紫外分光法检测乳酸脱氢酶、肌酸激酶、超氧化物岐化酶的活性和丙二醛的含量,电化学免疫发光法检测肌钙蛋白水平.结果 动脉粥样硬化组乳酸脱氢酶和肌酸激酶活性、丙二醛含量和肌钙蛋白水平、细胞凋亡指数以及CaSR、Bax和caspase-3的表达均高于对照组,而超氧化物岐化酶活性则低于对照组,Bcl-2表达低于对照组,心肌细胞超微结构损伤严重.结论 高脂血症和动脉粥样硬化可引起大鼠心肌CaSR的表达增加和细胞凋亡,其机制与心肌缺血所致的氧化应激有关.     

吡格列酮对高脂血症大鼠主动脉血凝素样氧化型低密度脂蛋白受体1和凋亡蛋白表达的影响

目的 观察吡格列酮对高脂血症大鼠主动脉血凝素样氧化型低密度脂蛋白受体1 (LOX-1)和凋亡蛋白Bax、Bcl-2表达的影响,并探讨其作用机制及LOX-1在吡格列酮调节凋亡蛋白Bax、Bcl-2表达中的作用.方法 清洁型SD大鼠26只,随机分为对照组(n=9)、高脂饮食组(n=17),高脂饮食组喂养12周后再随机分为模型组(n=8)和吡格列酮组(n=9),分别干预4周后,检测各组血脂水平,HE染色观察主动脉病理形态学改变,免疫组织化学法检测主动脉LOX-1、Bax和Bcl-2的表达.结果 高脂饮食组喂养12周后,血脂明显升高(P＜0.01);给药4周后,与模型组比较,吡格列酮组甘油三酯、总胆固醇水平明显降低(P＜0.01),且主动脉血管内皮基本完好,偶有脱落,平滑肌细胞增殖不明显.与对照组相比,模型组主动脉LOX-1和Bax蛋白表达明显升高(P＜0.01),Bcl-2蛋白表达和Bcl-2/Bax比值显著降低(P＜0.01);与模型组相比,吡格列酮组主动脉LOX-1和Bax蛋白表达明显降低(P＜0.01),Bcl-2蛋白表达和Bcl-2/Bax比值明显升高(P＜0.01).结论 高脂饮食可引起主动脉LOX-1和凋亡蛋白Bax、Bcl-2及Bcl-2/Bax比值的改变,而吡格列酮可降低血脂,调节LOX-1和凋亡蛋白表达,抑制内皮细胞凋亡,从而改善内皮细胞功能和动脉粥样硬化病理进程.     

吡格列酮对高脂血症大鼠主动脉内皮细胞凋亡的作用

目的观察吡格列酮对高脂血症大鼠主动脉内皮细胞凋亡的影响,并探讨其可能的作用机制。方法清洁型SD大鼠26只,随机分为健康对照组(9只)、高脂饮食组(17只),高脂饮食组喂养12周后再随机分为模型组(8只)和吡格列酮组(9只),4周后,检测各组血脂水平,通过免疫组织化学法检测主动脉Bcl-2、Bax的表达,TUNEL染色法观察主动脉内皮细胞凋亡情况,计算细胞凋亡指数。结果 (1)高脂饮食组喂养12周后,血脂明显升高;给药4周后,与模型组比较,吡格列酮组TG、TC水平明显降低(P=0.000);(2)与健康对照组相比,模型组主动脉Bax蛋白表达明显增高(P=0.003),Bcl-2蛋白表达和Bcl-2/Bax比值明显降低(P=0.000);与模型组相比,吡格列酮组主动脉Bax蛋白表达明显降低(P=0.000),Bcl-2蛋白表达(P=0.001)和Bcl-2/Bax比值明显升高(P=0.000),且吡格列酮组主动脉内皮细胞凋亡指数较模型组明显降低,差异有统计学意义(17.5633±7.0584比6.0475±2.2370,P=0.000)。结论吡格列酮可改善高脂血症大鼠血脂水平,调节凋亡蛋白表达,减少主动脉内皮细胞凋亡。     

Ghrelin对棕榈酸诱导的大鼠主动脉内皮细胞凋亡的影响

目的探讨Ghrelin能否抑制棕榈酸诱导的大鼠主动脉内皮细胞凋亡。方法大鼠主动脉内皮细胞分别在含0.3 mmol/L棕榈酸的脂性培养基中孵育24 h,培养基中加或不加Ghrelin,应用MTT法检测细胞活性,Ho-echst 33258及流式细胞仪AnnexinⅤ-FITC/PI双染法检测细胞凋亡,分光光度计检测Caspase-3活性,Western Blot检测Bcl-2和Bax表达。结果棕榈酸降低细胞活性,使细胞凋亡增加至30.03%,与对照组(5.01%)相比差异有统计学意义(P<0.01),棕榈酸增加Caspase-3活性,使Bcl-2/Bax比率下降。Ghrelin能够浓度依赖性增加细胞活性,10 nmol/L是最低有效浓度,100 nmol/L时作用最显著。Ghrelin能抑制棕榈酸诱导的内皮细胞凋亡,使凋亡率降至10.03%(P<0.05)。同时Ghrelin降低Caspase-3活性并增加Bcl-2/Bax比率。结论 Ghrelin可以抑制棕榈酸诱导的血管内皮细胞凋亡,可能在棕榈酸诱导的内皮细胞损伤中发挥保护作用。     

吡格列酮对高脂血症大鼠核转录因子kB活性和主动脉凋亡蛋白表达的影响

目的 观察吡格列酮对高脂血症大鼠NF-κB活性和主动脉凋亡蛋白Bax、Bcl-2表达的影响.方法 SD大鼠26只,随机分为对照组9只、高脂饮食组17只.高脂饮食组喂养12周后再随机分为模型组8只和吡格列酮组9只,干预4周后,检测各组血脂;HE染色观察主动脉组织形态学改变;免疫组织化学法检测NF-κB p65、Bax、Bcl-2 表达.结果 与对照组比较,高脂饮食组12周后,TG、TC、LDL-C明显升高(P＜0.01);与模型组比较,16周后,吡格列酮组TG、TC明显降低(P＜0.01);与对照组比较,模型组NF κB p65、Bax明显升高,Bcl-2和Bcl-2/Bax比值明显降低(P＜0.01);与模型组比较,吡格列酮组NF-κB p65、Bax明显降低,Bcl-2和Bcl-2/Bax比值明显升高(P＜0.01).结论 高脂饮食可引起主动脉凋亡蛋白Bax、Bcl-2及Bcl-2/Bax比值的改变,可能与NF-κB活性增加相关.吡格列酮可减少NF-κB p65表达,调节Bax、Bcl-2表达,从而改善内皮细胞功能和动脉粥样硬化病理进程.     

血管紧张素原对动脉粥样硬化的作用及机制

目的探讨血管紧张素原(AGT)对动脉粥样硬化(AS)的作用机制。方法构建AS小鼠模型,RT-PCR检测AS小鼠斑块组织和正常小鼠主动脉血管组织中AGT的表达水平。以人巨噬细胞RAW264.7和人主动脉平滑肌细胞(HA-VSMC)为研究对象,转染siRNA AGT、siRNA control,实时荧光定量PCR(RT-PCR)检测转染后的AGT水平。MTT检测细胞转染后细胞的增殖情况,流式细胞仪检测转染后的细胞凋亡情况。Western印迹检测转染后细胞中Caspase-3、Bcl-2、Bax蛋白表达水平。结果 AS小鼠斑块组织中AGT的表达水平高于正常小鼠主动脉组织(P<0.01)。siRNA AGT可以有效抑制巨噬细胞RAW264.7和人主动脉平滑肌细胞HA-VSMC中AGT的转录表达。转染siRNA AGT后的巨噬细胞RAW264.7存活率与siRNA control组比较差异显著(P<0.01),转染siRNA AGT后的主动脉平滑肌细胞HA-VSMC存活率与siRNA control组差异显著(P<0.01),抑制AGT的表达可以抑制巨噬细胞和平滑肌细胞的增殖。转染siRNA AGT后的巨噬细胞RAW264.7凋亡率显著高于siRNA control组(P<0.01);转染siRNA AGT后的主动脉平滑肌细胞HA-VSMC凋亡率显著高于siRNA control组(P<0.01)。转染siRNA AGT后的巨噬细胞RAW264.7和主动脉平滑肌细胞HA-VSMC中Caspase-3、Bax蛋白表达量显著高于siRNA control组,Bcl-2蛋白表达量显著低于siRNA control组(均P<0.01)。结论AGT在鼠AS斑块组织中过表达,抑制AGT可以抑制AS相关细胞增殖,促进细胞凋亡,作用机制与凋亡相关蛋白Caspase-3、Bcl-2、Bax有关。     

通心络对家兔血管成形术后平滑肌细胞凋亡及Bcl-2和Bax蛋白表达的影响

目的观察通心络对血管成形术后家兔平滑肌细胞凋亡及凋亡相关基因Bcl-2和Bax蛋白表达的影响。方法60只家兔随机分为对照组、高脂组及通心络组(每组20只)。通过两次球囊损伤加高脂饮食制备家兔血管成形术模型,再进行4周的通心络治疗观察,以缺口末端标记法(TUNEL)检测凋亡细胞变化,以免疫组化法检测Bcl-2及Bax蛋白表达的变化。结果高脂组家兔血管平滑肌细胞(VSMC)的凋亡较对照组减少,通心络组细胞凋亡明显多于高脂组。高脂组Bcl-2的阳性表达较对照组明显升高,主要分布于内膜及中膜附近;通心络治疗组Bcl-2表达下降,Bcl-2阳性细胞光密度与对照组及高脂组相比差异有统计学意义。通心络组Bax阳性表达显著高于高脂组,主要位于内膜附近。结论通心络具有促进VSMC凋亡,下调Bcl-2蛋白表达及上调Bax蛋白表达的作用。     

SIRT1抑制剂sirtinol对前列腺癌DU145细胞凋亡的影响及可能机制

目的观察SIRT1抑制剂sirtinol对前列腺癌DU145细胞系细胞凋亡和细胞凋亡关键调控因子(Bcl-2、Bax、Cytochrome C和Caspase-3)表达变化的影响,探讨SIRT1在前列腺癌发生的可能机制。方法体外培养DU145细胞,实验分对照组(DMSO组)和sirtinol组(终浓度为10,25和50μmol/L),Western印迹检测DU145细胞SIRT1蛋白表达水平;流式细胞术检测细胞凋亡;Western印迹检测DU145细胞中细胞凋亡关键调控因子Bcl-2、Bax、Cytochrome C和Caspase-3的蛋白表达。结果与对照组相比,随着sirtinol浓度的增加,SIRT1蛋白表达水平逐渐降低,细胞凋亡比例增加,诱导细胞发生凋亡。不同浓度sirtinol作用DU145细胞后Bcl-2蛋白表达减少,且随剂量增加表达越低;Bax蛋白表达增加,Bcl-2/Bax比率降低;伴随Cytochrome C的释放和Caspase-3的激活。结论下调SIRT1表达诱导前列腺癌细胞DU145细胞凋亡,其机制可能与改变细胞凋亡关键调控因子Bcl-2、Bax、Cytochrome C和Caspase-3的蛋白表达相关。     

沥水调脂胶囊对氧化型低密度脂蛋白诱导内皮细胞凋亡及Bcl-2、BaX、P53和Caspase-3蛋白表达的影响

目的：研究沥水调脂胶囊抑制内皮细胞凋亡的机制。以氧化型低密度脂蛋白诱导人脐静脉内皮细胞凋亡，观察Bcl-2,Bax,P53和Caspase-3蛋白表达。方法：用流式细胞术检测细胞凋亡并进行周期分析；用细胞免疫荧光标记结合流式细胞术检测Bcl-2,Bax,P53和Caspase-3蛋白表达水平。结果：沥水调脂胶囊对氧化型低密度脂蛋白诱导的内皮细胞凋亡有抑制作用。在此过程中沥水调脂胶囊上调了Bcl-2蛋白表达水平，对Bax蛋白表达未见明显影响，同时下调了P53和Caspase-3蛋白表达水平。结论：推测沥水调脂胶囊可能是通过上调Bcl-2蛋白表达，下调P53和Caspase-3蛋白表达抑制内皮细胞凋亡的。     

老年高血压患者血压昼夜节律与颈动脉粥样硬化的相关性研究

目的探讨老年高血压患者血压昼夜节律与颈动脉粥样硬化的相关性。方法2003￣2004年来我院老年高血压患者共72例(男68例女4例),根据动态血压监测(ABPM)结果分为正常昼夜节律组,即杓型组(n=37,男35例女2例)和异常昼夜节律组,即非杓型组(n=35,男33例女2例)。对所有患者均行颈动脉超声检查,测定右侧颈总动脉(RCCA)、颈内动脉(RICA)内膜中层厚度(IMT)、管腔内径(D),并计算各自的IMT/D值,测定右侧颈动脉分叉处(RBIF)的IMT,观察并记录双侧颈动脉系统斑块的大小、数量。结果(1)两组年龄(Age)、体重指数(BMI)、总胆固醇(TC)、甘油三酯(TG)、全天平均收缩压(24hMSP)、全天平均舒张压(24hMDP)比较均无显著性差异(P>0.05)。(2)两组的RCCA及RICA的IMT、D、IMT/D比较均无显著性差异(P>0.05)。而右颈动脉分叉处IMT,非杓型组明显高于杓型组(P<0.001)。(3)两组总斑块检出率无显著差异,但多发性斑块检出率非杓型组显著高于杓型组(P<0.05)。结论老年高血压患者血压昼夜节律与颈动脉粥样硬化明显相关,异常的血压昼夜节律提示可能存在更严重的靶器官损害。     

慢性肾衰竭患者同型半胱氨酸血症与动脉粥样硬化的关系

目的　研究慢性肾功能衰竭 (CRF)患者血浆同型半胱氨酸 (Hcy)水平与动脉粥样硬化及动脉舒张功能障碍的关系。方法　选择CRF患者 197例和健康对照 5 3例 ,采用荧光偏振免疫分析法测定血浆总同型半胱氨酸 (tHcy)水平 ,用高分辨超声技术检测颈总动脉内膜 中层厚度 (IMT)、粥样硬化斑块以及反应性充血后和含服硝酸甘油后肱动脉内径的变化率。结果　CRF患者高同型半胱氨酸血症发生率为 84 4 % ,其血浆tHcy水平 [(2 3 5 6± 11 91) μmol/L]明显高于正常对照组 [(7 97±2 6 5 ) μmol/L](P <0 0 1)。CRF患者平均IMT值和颈动脉粥样斑块检出率均明显高于年龄匹配的正常对照组 ,肱动脉反应性充血后内径增加率 (Dh)为 (4 0 5± 3 81) % ,含服硝酸甘油后内径增加率 (Dn)为 (4 94± 4 2 8) % ,均分别明显低于正常对照组Dh的 (8 81± 6 15 ) %和Dn 的 (11 72± 7 6 4 ) % (P <0 0 1)。按动脉粥样硬化严重程度分级 ,病变越重者血浆tHcy水平越高。多因素逐步回归分析显示 ,影响颈总动脉IMT的因素按影响程度依次为血浆tHcy、透析时间和年龄 (RR =0 4 84 ,P <0 0 0 1) ;影响Dh 的因素为血浆tHcy水平、年龄、透析时间和血清总胆固醇水平 (RR =0 2 6 3,P <0 0 0 1) ;影响Dn 的因素为年龄和血浆tHcy水平 (RR =0 2     

Prevalence of femoral atherosclerosis in asymptomatic men with hyperlipoproteinaemia

Sixty-two male subjects with primary hyperlipoproteinaemia of type IIA (n = 18), type IIB (n = 18) or type IV (n = 24) underwent femoral arteriography to investigate the degree of atherosclerosis. All except two were free from symptoms of peripheral arterial disease. The presence of atheroma was determined according to a standardized consensus procedure based on visual interpretation. Atherosclerosis were graded by means of a scoring system, whereby an overall atherosclerosis score (OAS) was calculated for each patient, based on four consecutive segments of the femoral artery. Thirteen type IIA (72%), 14 type IIB (78%) and 18 type IV (75%) patients had femoral atherosclerosis, and the mean OAS in the patients with hyperlipoproteinaemia of these types were 0.58, 0.75 and 0.49, respectively, all with a standard error of the mean about 0.05. The atherosclerosis score increased the more distal the arterial segment, being most prevalent in the lower inferior segment. The OAS was higher in patients of above median age, in those with systolic or diastolic blood pressure above the median and in smokers. Multiple stepwise regression analysis showed that low density lipoproteins cholesterol was highly significantly related to OAS among smokers. In conclusion, femoral atherosclerosis is a prevalent finding in asymptomatic subjects with hyperlipoproteinaemia and could serve as a basis for intervention studies.     

老年2型糖尿病患者颈动脉粥样硬化与血清25-羟维生素D_3水平的关系

目的探讨血清25-羟维生素D3[25(OH)D3]与老年2型糖尿病患者颈动脉粥样硬化发生、发展的相关性。方法选择2型糖尿病患者174例,根据颈动脉内膜中层厚度(IMT)水平分为IMT正常组84例,IMT增厚组90例;又根据颈动脉有无狭窄分为颈动脉无狭窄组141例,颈动脉狭窄组33例。测量血压、身高、体重,计算体质量指数(BMI),并检测空腹血糖、血脂、糖化血红蛋白等指标,采用酶联免疫分析法测定血清25(OH)D3水平。超声检测及计算IMT及狭窄情况。结果 IMT增厚组血清25(OH)D3水平明显低于IMT正常组(P<0.05);颈动脉狭窄组血清25(OH)D3水平明显低于颈动脉无狭窄组,空腹血糖、尿酸水平明显高于颈动脉无狭窄组(P<0.05)。相关分析显示,颈动脉IMT最大值与老年2型糖尿病患者25(OH)D3呈负相关(P<0.05),与尿酸呈正相关(P<0.01)。logistic回归分析显示,颈动脉狭窄与25(OH)D3、尿酸独立相关。结论在老年2型糖尿病患者中,低水平血清25(OH)D3可能是颈动脉粥样硬化的独立危险因素。     

The adventitia of atherosclerotic coronary arteries frequently contains Chlamydia pneumoniae.

The presence of Chlamydia pneumoniae in the human arterial system has mainly been determined in atherosclerotic plaque, whereas the adventitia has remained relatively unexplored. We assessed the presence of C. pneumoniae in all three vessel wall layers of coronary (n=72) and brachial (n=48) arteries in relation to local atherosclerosis. Immunohistochemical staining of C. pneumoniae was observed in plaque and adventitia. Cells stained for C. pneumoniae were detected in the same areas as cells stained for macrophages in adjacent sections. C. pneumoniae staining in the adventitia was associated with the extent and severity of atherosclerosis. Coronary sections with C. pneumoniae staining in both adventitia and plaque more often contained advanced atherosclerosis than sections with staining only in the adventitia. Staining was observed more often in the coronary artery than in the brachial artery (24/72 vs. 5/48 and 51/72 vs. 8/48 for plaque and adventitia, respectively, P=0.004 and P<0.001). PCR confirmed the presence of C. pneumoniae DNA in the adventitia. In summary, the adventitia of atherosclerotic coronary arteries frequently contains C. pneumoniae that seems to be located within macrophages. These results might indicate a possible route for infected circulating macrophages to home into atherosclerotic lesions in the artery via vasa vasorum.     

The relation between plasma cysteine, plasma homocysteine and coronary atherosclerosis

Several studies have reported that elevated plasma levels of total homocysteine (tHcy) are related to an increased risk of cardiovascular disease. Only a few studies have looked at the effect of cysteine, another amino thiol, on cardiovascular disease risk. Therefore, in the present case-control study we compared plasma total cysteine (tCys) levels and plasma tHcy levels among subjects with severe coronary atherosclerosis (cases, n=131), subjects without severe coronary atherosclerosis (coronary controls, n=88) and healthy subjects (population-based controls, n=101). Cases were defined as those having > or =90% occlusion in one and > or =40% occlusion in a second coronary artery, while coronary controls had a maximum of 50% occlusion in only one coronary artery. Both males and females, aged 26--64 years were studied. We have previously reported that plasma tHcy is an independent risk factor for coronary atherosclerosis in this study population. In the present analysis, we found that cases had statistically significant higher mean plasma tCys levels than coronary controls and population-based controls (295.8+/-40.2, 279.0+/-35.5 and 282.6+/-32.4 micromol/l, respectively). The odds ratio (OR) of coronary atherosclerosis for the upper tertile of tCys compared with the bottom tertile was 2.5 (95% confidence interval (CI), 1.4--4.3). However, the association between tCys and coronary atherosclerosis was confounded to a great extent by risk factors (OR, 1.0; 95% CI, 0.5--2.0). The multivariate adjusted OR of coronary atherosclerosis per 1 S.D. increase in plasma tCys was 1.0 (95% CI, 0.8--1.3). The corresponding OR per 1 S.D. increase in plasma tHcy was 1.4 (95% CI, 1.1--1.8). We conclude that plasma tCys, unlike plasma tHcy, is not an independent risk factor for atherosclerosis.     

脑动脉粥样硬化患者沟宽与脑回厚度在预测血管性认知功能障碍作用研究

目的探讨脑动脉粥样硬化患者沟宽与脑回厚度在预测血管性认知功能障碍(VCI)的价值。方法选取120例脑动脉粥样硬化患者,根据是否患有VCI分成VCI组48例和非VCI组72例,收集2组一般临床资料,用头颅MRI检查,并计算左侧颞上回厚度和左侧胼胝体沟宽度,用Spearman相关分析左侧颞上回厚度、左侧胼胝体沟宽度与蒙特利尔认知评估量表(MoCA)评分相关性,采用logistic多因素回归分析影响因素。结果VCI组年龄、高血压比例及左侧胼胝体沟宽度明显高于非VCI组(P<0.01),MoCA评分和左侧颞上回厚度明显低于非VCI组[(20.3±2.3)分vs(26.8±3.4)分,P=0.000;(1.6±0.3)mm vs(1.9±0.4)mm,P=0.000]。Spearman相关性分析显示,左侧颞上回厚度与MoCA评分呈正相关(r=0.273,P=0.031),左侧胼胝体沟宽度与MoCA评分呈负相关(r=-0.323,P=0.027)。年龄、受教育年限、左侧颞上回厚度以及左侧胼胝体沟宽度与脑动脉粥样硬化患者VCI相关(P<0.05,P<0.01)。结论脑动脉粥样硬化合并VCI患者的左侧颞上回厚度以及左侧胼胝体沟宽度发生改变,左侧颞上回厚度以及左侧胼胝体沟宽度可能作为脑动脉粥样硬化患者发生VCI的预测指标。     

酮替芬对Wistar大鼠动脉粥样硬化的干预研究

目的观察酮替芬(Ket)对动脉粥样硬化形成的干预作用。方法将40只雄性Wistar大鼠随机分为4组,即A组[高脂+维生素D_3(VitD_3)]、B组[高脂+VitD_3+Ket]、C组[高脂+VitD_3+卵蛋白(OVA)]和D组(高脂+VitD_3+OVA+Ket)。A组常规建立动脉粥样硬化模型,C组在常规高脂的基础上加用OVA激活肥大细胞建立动脉粥样硬化模型,B、D两组分别在A、C组建立动脉粥样硬化的过程中给予Ket干预。实验完毕后,分别对A、B组以及C、D组斑块病理形态及斑块中肥大细胞的分布情况进行比较。结果 (1)A、C组动脉粥样硬化病理改变分别较B、D组为重,可见典型AS及不稳定AS改变;B、D组Ket药物干预达到预期效果;(2)动脉粥样硬化斑块中的肥大细胞分布密度A组比B组:5.00±1.41比2.88±1.25,P<0.05;C组比D组:8.00±1.29比5.86±2.03,P<0.05,差异均有统计学意义;(3)实验结束时测定大鼠血清白介素(IL)-6水平,A组比B组:(60.18±8.15)ng/L比(41.52±6.71)ng/L,P<0.05;C组比D组:(90.66±8.18)ng/L比(68.32±5.92)ng/L,P<0.05,差异均有统计学意义。结论高脂+VitD_3+OVA能够建立较为成熟、更符合人类动脉粥样硬化病理形态的大鼠模型;肥大细胞在动脉粥样硬化的形成中有着重要作用,是动脉粥样硬化形成的重要炎症细胞;全身性的肥大细胞活化对斑块形成有促进作用;Ket有抑制炎症因子活化的作用,对斑块形成及失稳定有预防作用。     

Angiotensin converting enzyme gene deletion allele is independently and strongly associated with coronary atherosclerosis and myocardial infarction.

OBJECTIVE--To investigate the association of the three angiotensin converting enzyme (ACE) genotypes, DD, ID, and II, with the occurrence or absence of coronary atherosclerosis and with myocardial infarction and hypertension. DESIGN--Cohort analysis study. SETTING--North-Italy reference centre. SUBJECTS--388 white Italian patients (281 males; mean age 60.7 (SD 12.5) years) with proven coronary atherosclerosis (n = 255) or with angiographically normal coronary arteries (n = 133). A further group of 290 healthy blood donors was tested for allele frequency comparison. INTERVENTIONS--ACE/ID polymorphism was analysed with polymerase chain reaction on DNA from white blood cells. MAIN OUTCOME MEASURES--Coronary atherosclerosis, myocardial infarction, hypertension. RESULTS--The D and I allele frequencies were respectively 0.63 and 0.37 in the overall healthy blood donor group and 0.66 and 0.34 in the overall study group. In the latter, univariate analysis showed (1) that coronary atherosclerosis (255 patients) was associated with the deletion allele, with an odds ratio (OR) of 5.78 for DD/II, P < 0.001, and 2.39 for ID/II, P = 0.006; and (2) that myocardial infarction (154 patients) was associated with the DD genotype (OR DD/II = 2.56, P = 0.007), but not with the ID genotype (OR DD/II = 1.96, P = 0.056). Finally, hypertension proved to be unrelated with the ACE genotype. The distribution between the three genotypes of known risk factors for coronary artery disease was similar. Logistic regression modelling, performed to test the association of the selected risk factors simultaneously with coronary atherosclerosis and myocardial infarction, showed that the deletion allele (whether DD or ID) was the strongest risk factor for atherosclerosis, and that the D allele was significantly associated with the risk of infarction (although to a lesser extent than with coronary atherosclerosis). CONCLUSION--ACE deletion polymorphism is strongly and independently associated with coronary atherosclerosis and, to a lesser extent, with myocardial infarction. As such, the results are analogous to what has already been reported in French white, Japanese, and Welsh coronary patients.