六味地黄丸对糖尿病大鼠血管功能的影响及抗氧化应激机制

目的观察六味地黄丸(LWDHP)对糖尿病(DM)大鼠血管功能及抗氧化应激的作用,探讨LWDHP在DM血管病变中的保护机制。方法雄性SD大鼠随机分为正常对照组、DM模型组和LWDHP治疗组(1.2 g/kg),每组10只。高脂饲料配合小剂量链脲佐菌素(STZ)30 mg/kg建立2型糖尿病(T2DM)大鼠模型。治疗8 w后分离胸主动脉,观察血管的舒张功能;试剂盒检测血管组织中丙二醛(MDA)的浓度和一氧化氮(NO)的含量;RT-PCR及Western印迹检测血管组织中蛋白质精氨酸甲基转移酶1(PRMT)1 mRNA和蛋白的表达。结果与正常对照组比较,T2DM大鼠主动脉内皮依赖性舒张功能和血管组织中NO的含量显著下降,MDA浓度增加(P0.01)。LWDHP治疗可有效地减轻DM大鼠血管内皮功能障碍,增加NO的含量和降低MDA的含量(P0.01)。同时DM大鼠血管组织中PRMT1 mRNA和蛋白的表达量显著升高(P0.01),LWDHP治疗后PRMT1 mRNA和蛋白的表达量明显下降(P0.01)。结论 LWDHP可显著改善T2DM大鼠的血管内皮舒张功能障碍,通过调节MDA/PRMT1/NO的表达,抑制氧化应激损伤而保护血管内皮。     

秋水仙碱对烟草侧流烟雾导致的大鼠主动脉氧化应激和内皮功能不全的保护作用

目的：探讨秋水仙碱对大鼠主动脉氧化应激和内皮功能的影响。方法制备吸入烟草侧流烟雾的大鼠模型,同时通过管饲法给大鼠服用秋水仙碱。56d实验结束后,测定大鼠主动脉中超氧化物歧化酶（SOD）活力,丙二醛（MDA）、一氧化氮（NO）、内皮型一氧化氮合酶（eNOS）含量,以及进行内皮依赖的主动脉舒张实验,观察秋水仙碱对烟草烟雾导致的大鼠主动脉氧化应激和内皮功能改变的影响。结果与对照组相比,吸入烟草侧流烟雾大鼠组中MDA含量明显升高,NO、eNOS含量以及SOD活力下降,主动脉舒张功能受损,而服用秋水仙碱的大鼠可明显改善这些异常改变（P＜0.05）。结论（1）吸入烟草侧流烟雾可引起大鼠主动脉内皮氧化应激和内皮功能不全;（2）经秋水仙碱治疗后,可改善大鼠主动脉内皮氧化应激和受损的内皮功能。     

ATP敏感钾通道在丹参酮ⅡA对抗高糖诱导血管内皮功能损伤中的作用

目的探讨ATP敏感钾通道(KATP)在丹参酮ⅡA(TSA)对抗高糖诱导血管内皮功能损伤中的作用。方法采用离体血管环灌流方法,检测高糖诱导大鼠血管内皮依赖性舒张功能损伤以及血管组织中一氧化氮(NO)、丙二醛(MDA)含量和超氧化物歧化酶(SOD)活性和KATP抑制剂格列本脲(Gly)对TSA的作用。结果高糖显著降低了大鼠血管内皮依赖性舒张反应,TSA以浓度依赖的方式抑制了高糖诱导的损伤。高糖显著降低了血管组织中NO含量和SOD活性而增加了MDA含量,TSA逆转了高糖的作用,而Gly部分取消了TSA的作用。结论 TSA能对抗高糖诱导的血管内皮依赖性舒张功能损伤,其机制可能与TSA增加NO的释放,抑制氧化应激有关;Gly能部分地阻断TSA的这种保护作用。     

罗格列酮对2型糖尿病大鼠主动脉内皮依赖性血管舒张功能的影响

目的观察2型糖尿病（T2DM）大鼠胸主动脉内皮依赖性血管舒张功能和一氧化氮（NO）、一氧化氮合酶（eNOS）的变化及罗格列酮（RSG）治疗对其内皮功能的影响。方法SD大鼠经高糖高脂喂养6周后予小剂量链脲佐菌素腹腔注射建立T2DM大鼠模型，糖尿病大鼠又分为对照（DM）组和RSG治疗组，RSG组用RSG干预8周，另选正常大鼠为正常对照（NC）组。实验终止时用正常葡萄糖高胰岛素钳夹技术的葡萄糖输注率（GIR）评价胰岛素抵抗，观察大鼠离体主动脉内皮依赖性血管舒张反应和主动脉NO、eNOS的变化。结果T2DM大鼠GIR、胸主动脉内皮依赖性血管舒张反应、主动脉NO含量及eNOS阳性表达较NC组显著降低（P〈0、01），RSG治疗后上述指标均显著升高（P〈0．05）。结论T2DM大鼠存在内皮依赖性血管舒张功能紊乱，RSG治疗可改善内皮功能，增强NO水平和eNOS的活性。     

顺气化痰活血方对慢性间歇性低氧大鼠主动脉内皮功能的干预作用

目的研究顺气化痰活血方对慢性间歇性低氧(CIH)大鼠主动脉内皮损伤的保护作用。方法采用间歇性低氧舱复制CIH大鼠模型,将60只大鼠随机分为对照组、模型组和中药组。离体血管灌流技术,观察乙酰胆碱(ACh)、硝普钠(SNP)对苯肾上腺素(PE)预收缩产生的舒张效应;HE染色观察主动脉内皮细胞的形态变化;Western印迹测定主动脉组织内皮素(ET)-1蛋白表达的变化;酶转化法测定主动脉组织中一氧化氮(NO)的含量。结果与对照组比较,CIH后大鼠主动脉内皮细胞受损,主动脉组织NO含量明显降低,ET-1蛋白表达明显增加,对ACh内皮依赖性舒张反应明显降低(P<0.01);经中药干预后,主动脉内皮细胞受损显著减轻,NO含量显著升高,ET-1蛋白表达显著减少,对ACh内皮依赖性舒张反应显著增强(P<0.01或P<0.05)。结论顺气化痰活血方可促进CIH大鼠主动脉NO分泌并抑制ET-1表达,恢复NO/ET-1平衡,有效保护内皮细胞形态及功能。     

复方丹参滴丸对心肌缺血—再灌注大鼠血管内皮功能的影响

将48只大鼠随机分为假手术组、缺血—再灌注（MIR）组和复方丹参滴丸组。对三组血浆内皮素（ET）、血清丙二醛（MDA）、一氧化氮（NO）含量及超氧化物歧化酶（SOD）活性进行检测和相关分析,并观察各组心肌毛细血管墨汁灌流数。结果与假手术组比较,MIR组SOD活性及NO含量均明显下降,MDA及ET含量均明显增加（P〈0.05,〈0.01）,原缺血部位心肌毛细血管墨汁灌流数明显减少（P〈0.01）;与MIR组比较,复方丹参滴丸组SOD活性及NO含量均明显升高,MDA及ET含量均明显降低（（P〈0.05,〈0.01）,原缺血部位心肌毛细血管墨汁灌流数明显增加（P〈0.01）。提示复方丹参滴丸能有效改善MIR大鼠的血管内皮功能,对缺血—再灌注心肌具有保护作用。     

α-硫辛酸降低糖尿病大鼠肾脏氧化应激水平

将大鼠分成正常对照（NC）组、糖尿病（DM）组及糖尿病加α-硫辛酸（DM＋ALA）组进行实验。4周后DM组24小时尿白蛋白（UAlb/24h）、肾重/体重（KW/BW）和丙二醛（MDA）含量均较NC组增加，总超氧化物歧化酶（TSOD）活性降低，谷胱甘肽过氧化物酶（GSH-Px）活性升高，过氧化氢酶（CAT）活性无变化；DM＋ALA组较DM组UAlb/24h、KW/BW和MDA水平降低，TSOD、GSH-Px和CAT活性无改变。结果说明，ALA能减低DM大鼠肾皮质氧化应激水平，延缓糖尿病肾病进展。     

肿瘤坏死因子相关的凋亡诱导配体对2型糖尿病大鼠内皮依赖性血管舒张功能的影响

目的 观察TNF相关的凋亡诱导配体（TRAIL）对T2DM大鼠主动脉内皮依赖性血管舒张功能的影响及其可能的机制. 方法 选取4周龄雄性SD大鼠,分为正常对照组（NC,n=10）与模型组（n=40）,随机将模型组分为T2DM亚组（n=10）与TRAIL亚组（TRAIL,n=10）.TRAIL干预6周后,检测各组FPG及FIns水平,计算ISI.检测NC组与TRAIL亚组血清TRAIL水平.观察大鼠离体主动脉内皮依赖性血管舒张反应,并检测主动脉一氧化氮（NO）含量、内皮型一氧化氮合酶活性（eNOS）.结果 与NC组比较,T2DM亚组FPG、FIns水平升高（P＜0.01）,ISI降低（P＜0.01）,血清TRAIL水平降低（P＜0.01）;血管内皮功能失调,乙酰胆碱（Ach）引起的血管最大舒张率降低（P＜0.01）,血管中NO含量及eNOS阳性表达降低（P＜0.01或P＜0.01）.TRAIL亚组血管Ach的舒张反应改善（P＜0.01）;血管中NO含量增加且eNOS阳性表达上调（P＜0.05或P＜0.01）;FPG、FIns降低,ISI提高（P＜0.01）. 结论 TRAIL改善T2DM大鼠内皮依赖性血管舒张功能的同时,可促进具有血管保护作用的NO生成.     

缬沙坦改善原发性高血压患者血管内皮功能

目的探讨缬沙坦对原发性高血压患者血管内皮功能的影响。方法36例原发性高血压患者口服缬沙坦80mg,1次/d。治疗8周前后,采用高分辨血管外超声法测定治疗前后肱动脉内皮依赖性血管舒张功能;采用硝酸还原法测定血清一氧化氮(NO),化学比色法测定血清超氧化物岐化酶(SOD)及丙二醛(MDA)即脂质过氧化物(LPO)浓度。选择26例正常人作为对照组。结果治疗前反应性充血引起的肱动脉变化与正常对照组比较明显减弱P<0.01,治疗后明显改善P<0.01。服用缬沙坦前与正常对照组的NO水平比较P<0.01,治疗后与治疗前相比较具有明显的提高P<0.01。治疗前与对照组相比SOD活性较对照组明显降低(P<0.01),MDA活性明显增高(P<0.01),经缬沙坦治疗后SOD活性较治疗前明显增高(P<0.01),MDA活性明显降低(P<0.01)。单因素相关分析显示:原发性高血压患者在进行缬沙坦治疗后反应性充血时肱动脉内径的变化与NO水平呈线性正相关P<0.01,r=0.798。结论缬沙坦可改善血管内皮依赖性舒张功能,减少氧化应激。     

阿托伐他汀对HTL导致大鼠血管内皮功能损伤的保护作用

目的探讨阿托伐他汀对同型半胱氨酸硫内酯(Homocysteine Thiolactone,HTL)所致在体大鼠血管内皮功能损伤的保护作用及其机制。方法采用HTL 50 mg/kg灌胃8 w的方法制造在体大鼠血管内皮损伤模型,同时治疗组给予阿托伐他汀10、40 mg/kg灌胃。8 w后检测血管内皮依赖性舒张反应、血清中一氧化氮(NO)、内皮素(ET)和降钙素基因相关肽(CGRP)的变化,丙二醛(MDA)的含量,超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)的活性。结果阿托伐他汀呈剂量依赖性地改善HTL抑制的大鼠胸主动脉的内皮依赖性舒张反应,增强血清中SOD、GSH-Px的活性,升高NO水平和CGRP,降低ET、MDA的含量,与HTL损伤组相比均有显著性差异(P<0.05;P<0.01)。结论阿托伐他汀对HTL所致在体大鼠血管内皮功能损伤具有显著保护作用,其作用机制可能与阿托伐他汀的抗氧化作用有关,而不依赖于其降脂的作用。     

瑞舒伐他汀改善糖尿病大鼠血管内皮功能的实验研究

目的 评价不同剂量瑞舒伐他汀对糖尿病大鼠血管内皮功能的保护作用.方法 24只糖尿病大鼠随机分为3组:糖尿病对照组、瑞舒伐他汀20 mg组(RV 20 mg组)和10 mg组(RV 10mg组);8只健康SD大鼠作为正常对照组.给药共8周,分别于给药前和给药后第8周测定血浆内皮素-1(ET-1)、一氧化氮(NO)、血糖、血脂含量.结果 用药前糖尿病大鼠各组血糖均显著高于正常对照组(P＜0.01);RV 20 mg和RV 10 mg组在给药后第8周血糖稍低于糖尿病对照组,但差异无统计学意义(P＞0.05).糖尿病对照组血浆NO浓度明显低于SD正常对照组(P＜0.05),给药8周后,用药组血浆NO浓度明显高于糖尿病对照组(P＜0.01或P＜0.05).糖尿病对照组血浆ET-1浓度高于SD正常对照组(P＜0.05);给药8周后,用药组血浆ET-1浓度明显低于糖尿病对照组(P＜0.01或P＜0.05).RV 20 mg组和RV 10 mg组比较,血浆E-1浓度降低及血浆NO浓度升高(P＜0.05).同时,RV 20 mg组和RV 10 mg组血胆固醇水平明显低于糖尿病对照组(P＜0.01).结论 瑞舒伐他汀可明显降低糖尿病大鼠的血胆固醇水平,同时通过提高血浆NO浓度和降低E-1浓度等机制改善血管内皮功能.

Abstract：

Objective To evaluate the effects of two different dosage of rosuvastatin on endothelial dysfunction in diabetic rats. Methods The 24 diabetic rats were randomly divided into three groups (n=8,each): diabetic control group, 20 mg rosuvastatin daily (RV 20 mg group) and 10mg rosuvastatin daily for 8 weeks (RV 10 mg group) and normal control group (SD group). The levels of blood glucose, lipid, nitric oxide(NO) and endothelin-1 (ET-1) were measured before and 8 weeks after treatment. Results The levels of blood glucose were higher in all diabetic rats groups than in SD group before experiment (P＜0. 01). Compared with diabetic rats control group, blood glucose was slightly lower in RV 10 mg group and RV 20 mg group at 8 weeks (P＞0. 05). The plasma NO level was significantly lower in diabetic rats control group than in SD group (P＜0. 05).After 8 weeks, plasma NO levels were significantly higher in RV 20 mg and RV 10 mg groups than in diabetic rats control group (P＜0. 01 or P＜0. 05). The plasma levels of ET-1 was significantly higher in diabetic rats control group than in SD group (P＜0. 01). After 8 weeks, plasma ET-1 levels were significantly lower in RV 20 mg and RV 10 mg group than in diabetic rats control group (P＜0. 01).Meanwhile, the plasma lipids were lower in RV 20 mg and RV 10 mg group than in diabetic control group (P＜0. 05 or P＜0. 01). Conclusions Rosuvastatin can adjust blood lipids and significantly improve endothelial function in diabetic rats by increasing plasma NO level and decreasing plasma ET-1 level.     

解聚复肾宁对糖尿病大鼠肾脏的保护作用

目的 观察中药复方解聚复肾宁(JJFSN)对糖尿病 (DM)大鼠肾脏的保护作用.方法 建立链脲佐菌素(STZ)诱导的DM大鼠模型,将成模大鼠随机分成4组:模型组、JJFSN组、厄贝沙坦组、JJFSN+厄贝沙坦组,并设正常对照组.各组大鼠采用相应的干预措施处理12 w.常规方法检测各组大鼠尿白蛋白排泄率(UAER)等指标,免疫组化法检测肾血管内皮生长因子(VEGF)和骨形成蛋白7(BMP-7)表达,Western印迹检测肾组织血小板衍化生长因子B(PDGF-B)的表达,透射电镜观察肾脏超微结构.结果 模型组大鼠除肾BMP-7表达显著减少外,其余指标均显著增高,肾脏超微结构改变明显;JJFSN组、厄贝沙坦组和JJFSN+厄贝沙坦组除肾BMP-7显著高于模型组(P＜0.05)外,其余指标均显著低于模型组(P＜0.05),肾脏超微结构改变明显改善;JJFSN+厄贝沙坦组各项指标改善明显优于模型组、JJFSN组和厄贝沙坦组(P＜0.05),但未达到正常对照组水平.结论 JJFSN对DM大鼠肾脏有明显保护作用.     

α-硫辛酸对链脲菌素诱发的大鼠胰岛β细胞损伤的保护作用

目的 研究α-硫辛酸(ALA)对链脲菌素(STZ)诱导的糖尿病大鼠胰岛β细胞损伤的保护作用.方法 30只SD大鼠按数字随机法分为正常对照组(NC组)、STZ组和ALA+STZ组(ALA组),各10只.后2组以STZ(70 mg/kg体重)一次性腹腔内注射诱发糖尿病,ALA组在注射前8 d开始给予ALA(50 mg·kg-1·d-1,强饲)直至实验结束(4周).STZ注射后每3天监测血糖、体重一次.测定胰腺匀浆中丙二醛(MDA)含量及还原型谷胱甘肽(GSH)水平,免疫组化方法检测胰岛β细胞内胰岛素水平.结果 STZ使大鼠血糖明显升高,STZ和ALA组制模成功率分别为90%(9/10)和70%(7/10),相差显著(P<0.05).实验结束时NC组、STZ组和ALA组平均体重分别为(368±3)g、(301±2)g和(341±26)g,3组间相差显著(P<0.05).STZ组胰腺组织内MDA水平为(1.22±0.14)nmol/mg prot,NC组为(0.57±0.04)nmol/mg prot,相差显著(P<0.05);STZ组胰腺组织内GSH含量为(16.54±1.10)mg/g prot,NC组为(25.46±0.62)mg/g prot(P<0.05);STZ组胰岛细胞呈退行性变.ALA组血糖较STZ组明显降低(P<0.05),胰腺组织匀浆MDA含量为(0.72±0.23)nmol/mg prot,较STZ组明显降低(P<0.05),GSH含量为(35.33 4±2.66)ms/s prot,较STZ组明显升高(P<0.05),胰岛的胰岛素分泌增强,较STZ组显著(P<0.05),胰岛β细胞损伤减轻.结论 ALA可通过减轻氧化应激来保护胰岛β细胞结构和功能的完整性.     

运动对糖尿病大鼠骨骼肌GLUT4和MAPK的作用

目的 研究适量运动对糖尿病大鼠骨骼肌葡萄糖转运蛋白（GLUT4）和丝裂素活化蛋白激酶（MAPK）活性的作用。方法 40只SD大鼠分为四组：糖尿病非运动组,糖尿病运动组,正常非运动组和正常运动组。运动组进行12周的中等强度的跑步训练。结果 （1）糖尿病大鼠血糖浓度增高,血胰岛素浓度降低;骨骼肌组织葡萄糖转运蛋白（GLUT4）含量下降,肝脏,胰腺和骨股长肌的丝裂素活化蛋白激酶（MAPK）活性下降,（2）糖尿病运动组大鼠经12周跑步训练后,血糖浓度下降,血胰岛素浓度升高;骨骼肌组织的GLUT4含量增加;肝脏,骨骼肌和胰腺的MAPK活性增加。结论 适量运动可增加骨骼肌GLUT4的蛋白含量以及增强肝脏和骨骼肌MAPK的活性,这可能是运动改善糖尿病糖代谢紊乱的机制之一。     

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.     

糖尿病大鼠胃窦胆碱能神经元与胃动力障碍的关系

目的 探讨链脲佐菌素(STZ)-糖尿病大鼠胃动力障碍和胃肌间神经丛胆碱能之间的关系.方法 45只SD大鼠随机分为对照组、糖尿病组和胰岛素组.成模后16 w测定大鼠胃动力,观察胃肌间神经丛胆碱能神经元的形态变化.结果 与对照组比较,糖尿病组大鼠胃动力减弱(P<0.01),胃窦肌间神经丛胆碱能神经元计数显著降低(P<0.01).与糖尿病组相比较,胰岛素组胃动力显著增高 (P<0.05),胃窦肌间神经丛胆碱能神经元平均光密度显著增高(P<0.05),胆碱能神经元计数有改善的趋势(P>0.05).结论 STZ-糖尿病大鼠胃动力障碍可能与胃肌间神经丛胆碱能神经损伤有关,胰岛素治疗能在一定程度上改善糖尿病胃动力障碍.     

Blood pressure changes associated with hyperinsulinemia or long-standing diabetes mellitus in spontaneously hypertensive rats

We studied the long-term change in blood pressures of spontaneously hypertensive rats (SHR) treated neonatally with streptozotocin (STZ). Two-day-old male SHR were injected intraperitoneally with 37.5–75.0 mg/kg STZ or with vehicle as control. STZ-treated SHR were divided into mildly or severely diabetic groups according to the nonfasting plasma glucose level at age 12 weeks (the former <300 mg/dl, the latter ≧300 mg/dl). In the mildly diabetic group (MD) (n = 5), body weight increased and nonfasting plasma glucose was normalized. At 52 weeks of age, fasting plasma glucose levels were lower than controls owing to hyperinsulinemia, and insulinomas were found in 60% of rats. The systolic blood pressure (SPB) as measured by a tail-cuff method, decreased after 40 weeks, and the mean BP from 44 to 52 weeks (188 ± 4 mmHg) was significantly lower than that in the control group (209 ± 3 mmHg, p < 0.01). In the severely diabetic group (SD) (n = 6), hyperglycemia persisted until 52 weeks, although its severity became less marked. BP in the SD group increased after 36 weeks, and the mean BP from 44 weeks to 52 weeks (224 ± 5 mmHg) was significantly higher than control (p < 0.05). The present study demonstrated that hypertension was ameliorated in SHR associated with hyperinsulinemia, and deteriorated with long-standing diabetes mellitus.     

脐血间充质干细胞移植对大鼠肺动脉高压的治疗作用研究

目的:观察脐血间充质干细胞(mesenchymal stem cells,MSCs)移植对SD大鼠肺动脉高压(PAH)的治疗作用。方法:将60只健康雄性SD大鼠随机分为4组,每组15只(n=15),即①正常对照组:不做任何处理;②模型组:以腹主动脉-腔静脉瘘分流术(abdominal aortocaval fistula shuning,A-VF)+单野百合碱(monocrotaline,MCT)注射建立大鼠PAH模型,故也可称为A-VF+MCT组;③干细胞移植组:在建立PAH模型后4周,经尾静脉注射Ho-echst 33342荧光染料标记的脐血MSCs,故此组也可称A-VF+MCT+MSCs组;④培养液对照组:在建立PAH模型后4周,经尾静脉注射培养脐血MSCs的培养液,故此组也可称为A-VF+MCT+培养液组。4周后以右心导管法测定平均肺动脉压(mPAP)、右心室肥厚指数[RVHI=RV/(LV+S)]、肺小动脉中层厚度占血管外径的百分比[MA(%)]和血管壁中层横截面积占血管总横截面积的百分比[MA(%)],观察肺小动脉重构情况。检测血流动力学、肺小动脉重塑及脐血MSCs的定植情况。结果:与正常对照组比较,造模实验证实,4周后A-VF+MCT组大鼠可形成典型的PAH,8周后mPAP明显增高,动脉中膜明显增厚,右心室出现明显肥厚;而A-VF+MCT+MSCs组大鼠mPAP、RV/(LV+S)、MT%和MA%均显著下降(P<0.01)。PAH大鼠死亡率从66.7%下降到13.3%。荧光显微镜观察显示脐血MSCs已成功定植到肺血管内膜。结论:以A-VF+MCT建立的大鼠PAH模型可形成重度PAH。脐血MSCs移植能显著降低肺动脉压力,减轻肺小动脉重构及右心室肥厚,显著降低PAH大鼠的死亡率。     

Effects of alpha-lipoic acid on microcirculation in patients with peripheral diabetic neuropathy.

Diabetic polyneuropathy is a serious complication in patients with diabetes mellitus. In addition to the maintenance of a sufficient metabolic control, alpha-lipoic acid (ALA) (Thioctacid, Asta Medica) is known to have beneficial effects on diabetic polyneuropathy although the exact mechanism by which ALA exerts its effect is unknown. In order to study the effect of ALA on microcirculation in patients with diabetes mellitus and peripheral neuropathy one group of patients (4 female, 4 male, age 60+/-3 years, diabetes duration 19+/-4 years, BMI 24.8+/-1.3 kg/m2) received 1200 mg ALA orally per day over 6 weeks (trial 1). A second group of patients (5 female, 4 male, age 65+/-3 years, diabetes duration 14+/-4 years, BMI 23.6+/-0.7 kg/m2) was studied before and after they had received 600 mg ALA or placebo intravenously over 15 minutes in order to investigate whether ALA has an acute effect on microcirculation (trial 2). Patients were investigated by nailfold video-capillaroscopy. Capillary blood cell velocity was examined at rest and during postreactive hyperemia (occlusion of the wrist for 2 minutes, 200 mmHg) which is a parameter of the perfusion reserve on demand. The oral therapy with ALA resulted in a significant decrease in the time to peak capillary blood cell velocity (tpCBV) during postocclusive hyperemia (trial 1: 12.6+/-3.1 vs 35.4+/-10.9 s, p<0.05). The infusion of ALA also decreased the tpCBV in patients with diabetic neuropathy (trial 2: before: 20.8+/-4,5, ALA: 11.74+/-4.4, placebo: 21.9-5.0 s, p<0.05 ALA vs both placebo and before infusions) indicating that ALA has an acute effect on microcirculation. Capillary blood cell velocity at rest (rCBV), hemodynamic parameters, hemoglobinA1c and local skin temperature remained unchanged in both studies. These results demonstrate that in patients with diabetic polyneuropathy ALA improves microcirculation as indicated by an increased perfusion reserve on demand. The observed effects are apparently acute effects. With the restriction of the pilot character of this investigation the findings support the assumption that ALA might exert its beneficial effects at least partially by improving microcirculation which is likely to occur also at the level of the vasa nervorum.     

The roles of MMP-2/TIMP-2 in extracellular matrix remodelling in the hearts of STZ-induced diabetic rats

OBJECTIVE: The present study was designed to examine the changes of MMP-2/TIMP-2 in the hearts of streptozotocin-induced diabetic rats and gain insight into their roles in extracellular matrix (ECM) remodelling on an experimental animal model of diabetic cardiomyopathy. METHODS AND RESULTS: Sixteen male Wistar rats were randomly divided into two groups: normal control and diabetic rats. Diabetes mellitus was induced in rats by streptozotocin injection. All rats were fed with standard chow and water ad libitum for 4 weeks. At 4 weeks diabetic rats were associated with a lower body weight (BW) and heart weight (HW) but a higher HW/BW. In the diabetic group, serum MMP-2 level had a tendency to increase but not significantly, while serum TIMP-2 significantly increased. Both the activity and expression of MMP-2 weakened in the hearts of diabetic rats. TIMP-2 gene expression in myocardium enhanced significantly. TIMP-2 protein level in diabetic heart was strengthened slightly but not significantly. VG staining showed a marked deposition of collagen in the diabetic group. Multivariate analysis revealed that total collagen content correlated negatively with the activity and gene expression of MMP-2 in the myocardium, and correlated positively with TIMP-1 mRNA expression. CONCLUSIONS: The decrease in MMP-2 activity and expression and increase in TIMP-2 gene expression in the myocardium of diabetic rats may lead to impairment of collagen degradation and contribute to the matrix deposition in diabetic myocardiopathy. The correlation between the serum level and cardiac expression of TIMP-2 in diabetic rats suggested that serum TIMP-2 level may be a viable marker for early diagnosis of diabetic myocardiopathy.