辛伐他汀保护高脂血症肾损害大鼠机制探讨

目的探讨辛伐他汀对高脂血症大鼠肾损害的保护机制。方法实验包括正常对照组、高脂血症模型组和辛伐他汀10mg/(kg.d)治疗组,12周后检测三组大鼠的血脂变化及观察尿蛋白水平,外周血及肾皮质NO浓度。结果高脂血症组尿蛋白明显高于正常对照组,血清及肾组织NO水平低于正常对照组。辛伐他汀治疗组总胆固醇(TC)、甘油三脂(TG)、低密度脂蛋白胆固醇(LDL-C)显著低于高脂血症组,且尿蛋白也显著低于高脂血症组,血清及肾组织NO含量高于高脂血症组。结论辛伐他汀在调脂的同时,促进NO的生成,降低尿蛋白。NO的增加可能是辛伐他汀保护高脂血症肾损害的重要机制之一。     

血脂康对自发性高血压大鼠血压及左室功能的影响

目的以原发性高血压大鼠(SHR)为实验模型,观察单纯使用血脂康对SHR血压、左室功能的影响,并探讨其相关机制。方法10周龄雄性SHR和WKY按试验和对照的原则分为三组:正常对照组(WKY),实验对照组(SHR),血脂康组(SHR-X,SHR服血脂康2400mg.kg-1.d-1),饲养16周后观察鼠尾收缩压(SBP),有创心功能,左心室心肌肥厚指数(LVM I),血浆内皮素-1(ET-1),肌浆网Ca2 -ATP酶活性(SERCA)。心肌细胞横径(TDM),心肌胶原含量及分布情况。结果SHR-X组较SHR组SBP低17.02mm Hg;左心室等容舒张期室内压下降的时间常数(T)显著降低[(1.01±0.09)m s,(2.38±0.59)m s,P<0.05];LVM I有明显下降[(3.07±0.25)mg/g,(3.31±0.23)mg/g,P<0.05]。ET-1有明显降低[(138±26pg/m l,(197±39)pg/m l,P<0.01),SERCA活性稍有升高。结论血脂康对延缓SHR血压的上升产生一定影响,有助于改善SHR左心室舒张功能,有助于抑制SHR左室肥厚。血脂康对心脏重构逆转的作用机制可能涉及血清ET-1水平下降,提高心肌细胞SERCA活性,抑制SHR心肌细胞内[Ca2 ]i超载等环节。     

The functional change of perivascular adipose tissue in hypertensive rats and its mechanisms

Background Recent studies have showed that perivascular adipose tissue (PVAT) may secrete the adventitial-derived relaxing factor (ADRF) to affect vascular function.However,the functional change of ADRF in hypertensive status is seldom studied;and the mechanisms of ADRF remain unclear.Our study examined the ADRF secreted by perivascular adipose tissue of control rats with normal blood pressure (Wistar Kyoto rats,WKY) and discussed the mechanisms of ADRF;We observed the functional change in ADRF of perivascular adipose tissue in spontaneously hypertensive rats (SHRs).Method The two adjacent thoracic aorta rings of SHR and WKY rats were divided into naked vessel subgroup and PVAT subgroup.The differences of vascular contractility between the two subgroups induced by 10-6 mmol/L phenylephrine were compared.The effect of PVAT culture medium of WKY on the vascular tension of Fat (-) vessels was observed by liquid transfer measure.The mechanism of ADRF was determined by tool drugs.Results In WKY group,vascular contractility of Fat (+) subgroup was lower than that of the Fat (-) subgroup (P < 0.05);while in SHR group,there was no difference between the two subgroups (P > 0.05).Transferring the incubation solution of WKY Fat (+) subgroup to the matched Fat (-) subgroup induced rapid vasodilation.When incubating blood vessels in calcium free PSS solution,there was no significant difference of phenylephrine-induced vasoconstriction between Fat (-) and Fat (+) subgroup.Both glibenclamide,the blocker of ATP-sensitive potassium (KATP) channel and Tetraethy-lammonium chloride (TEA),the inhibitor of calcium-dependent potassium (KCa) channel,effectively inhibited vasodilation function of ADRF.Conclusions Perivascular adipose tissue in WKY releases ADRF which can cause vasodilation,while this function was inhibited in SHR.ADRF acts through the activation of KCa and KATP channels and calcium ion is involved.     

阿托伐他汀联合还原型谷胱甘肽对高脂血症大鼠血脂代谢及抗氧化的影响

目的观察阿托伐他汀（Atorvastatin）联合还原性谷胱甘肽（reduced Glutathione,GSH）对高脂血症大鼠的抗氧化作用及血脂的影响。方法 SD雄性大鼠40只,随机分成5组,每组8只。A组：给予阿托伐他汀。B组：给予还原型谷胱甘肽。C组：给予阿托伐他汀＋还原型谷胱甘肽。D组：高脂血症对照组,给予高脂饲料灌胃。E组：空白对照组,给予普通饲料喂养。结果各药物干预组低密度胆固醇（LDL）,甘油三酯（TG）,血清总胆固醇（TC）,丙氨酸氨基转移酶（ALT）,天门冬氨酸氨基转换酶（AST）,丙二醛（Malondialdehyd,MDA）水平均低于高脂血症组（P〈0.05）,高密度胆固醇（HDL）,超氧化物歧化酶（Superoxide dismutase,SOD）水平均高于高脂血症组（P〈0.05）。C组与A组及B组比较作用更显著（P〈0.05）。结论还原型谷胱甘肽具有抗氧化作用外,还具有调脂作用,可能与阿托伐他汀具有协同作用。     

高血压合并IGT患者内皮素与颈动脉硬化的相关性研究

目的探讨原发性高血压合并糖耐量减低(IGT)患者的血浆内皮素及各相关因素血糖、胰岛素和颈动脉硬化之间的相关性及意义。方法选择157例原发性高血压患者分为单纯高血压组(1组),高血压合并IGT组(2组)和高血压合并糖尿病组(3组),另外选择33例健康人作对照组(0组)。分别对各组人员测定颈动脉中层厚度、血脂、血糖及血压等指标;采用放射免疫法测定内皮素、化学发光法测定胰岛素,HbAlc。结果 2组患者的内皮素水平较1组明显升高(P<0.01),但比3组的水平低(P<0.05);内皮素与IMT、空腹血糖、餐后2h血糖、胰岛素、胰岛素抵抗指数呈正相关,与HDL呈负相关。结论原发性高血压合并IGT患者的血浆内皮素与多种因素呈正相关,对其采取干预,纠正血浆内皮素水平异常状态、保护血管内皮功能、改善糖耐量水平对治疗原发性高血压合并IGT患者是有重大意义的有益措施。     

高血压病患者血管内皮依赖舒张功能变化与细胞内钙代谢的关系及氯沙坦的干预作用

为探讨血管内皮功能失调与细胞内钙超负荷的关系及氯沙坦的干预作用 ,选择原发性轻中度高血压病人 30例 ,正常血压对照组 30例 ,高血压组给予氯沙坦 5 0～ 10 0mg/d治疗 16周 ,治疗前后用高分辨超声测定肱动脉内皮依赖性血流介导舒张内径变化 ,用Fura 2荧光探针法测量细胞胞液游离钙浓度 ([Ca2 +]i)。结果发现 ,治疗前高血压组血流介导肱动脉舒张内径变化显著减少 ,[Ca2 +]i显著增加 ,且血流介导肱动脉舒张内径变化与 [Ca2 +]i呈显著负相关 ;治疗后血流介导肱动脉舒张内径变化显著增加 ,[Ca2 +]i显著下降 ,血流介导肱动脉舒张内径变化增加值与 [Ca2 +]i下降值呈显著正相关。本研究结果提示 ,原发性高血压病人血管内皮功能失调与细胞内钙超负荷密切相关 ,氯沙坦可能经过减轻细胞内钙超负荷而纠正内皮功能失调