可乐定对脑缺血大鼠单胺类神经递质和内皮素的影响

目的：探讨可乐定能否缓解脑缺血大鼠单胺类神经递质和内皮素水平的紊乱。方法：大鼠ｉｐ苯巴比妥３０ｍｇ／ｋｇ麻醉,结扎双侧锁骨下动脉及颈总动脉致全脑缺血,采用荧光法及放免法测定单胺类神经递质和内皮素水平。结果：大鼠缺血３０ｍｉｎ再灌６０ｍｉｎ,与假手术组相比,缺血组脑中去甲肾上腺素（ＮＥ）,５－羟色胺（５－ＨＴ）水平明显减少４２％及２４％,但ＤＡ水平明显上升３３％,同时,脑与血浆中内皮素水平分别升高９     

间质性肺疾病支气管肺泡灌洗液中内皮素的检测及其意义

目的　探讨内皮素 ( ET)在间质性肺疾病 ( ILD)发生发展中的作用及其诊断价值。方法　利用放射免疫直接测定法 ,检测 1 0例肺结节病和 8例特发性肺纤维化 ( IPF)患者外周血和支气管肺泡灌洗液 ( BALF)中内皮素的含量 ,并与 8例健康非吸烟者对照。结果　肺结节病和 IPF患者血浆和 BAL F中 ET的含量分别为 62 .1 4± 2 9.2 2 ng/L ,1 7.4 0± 2 .4 1 ng/L和 76.92± 71 .90 ng/L,1 0 .4 0± 3.1 3ng/L,均明显高于正常对照组 ( 2 0 .0 8± 8.37ng/L 和 4 .0 4± 0 .5 5 ng/L) ,P <0 .0 1 ;研究组 BALF中 ET与 Pa O2 呈负相关 ( r=- 0 .5 38,P<0 .0 1 ) ,与细胞总数呈正相关 ( r =0 .64 9,P <0 .0 1 )。其中结节病和 IPF的 BAL F中 ET水平分别与淋巴细胞和中性粒细胞呈明显正相关 ( r =0 .71 2 ,P <0 .0 1 ;r =0 .81 3,P <0 .0 1 )。结论　 ET在肺结节病和 IPF发生发展中起重要作用 ,并可做为判断疾病活动性的一项参考指标。     

No effect of a Taql polymorphism in DNA at the endothelin I (EDN1) locus on normal blood pressure level or variability

Endothelin is a peptide reported to be one of the most potent vasoconstrictors known. Presumably, endothelin could play a role in the physiological regulation of blood pressure in healthy or hypertensive people. We have studied a normal restriction fragment length polymorphism (RFLP) at the endothelin-I (EDN1) locus detected with the restriction enzyme TaqI. In three different series comprising 166, 120 and 207 unrelated individuals, we found no evidence for association between genotype in this polymorphism and level of systolic or diastolic blood pressure. In two series of 156 and 117 monozygotic (MZ) twin pairs, respectively, there was no difference between genotypes in within-pair variation in systolic or diastolic blood pressure. Thus neither "level gene" nor "variability gene" effects of normal genes at the EDN1 locus could be detected with the polymorphism analyzed, in healthy population samples.     

Impaired cerebral autoregulation 24 h after induction of transient unilateral focal ischaemia in the rat

Cerebral blood flow (CBF) and cerebral autoregulation have been investigated 24 h after transient focal ischaemia in the rat. Cerebral blood flow was measured autoradiographically before and during a moderate hypotensive challenge, to test autoregulatory responses, using two CBF tracers, (99m)Tc-d,l-hexamethylproyleneamine oxide and 14C-iodoantipyrine. Prior to induced hypotension, CBF was significantly reduced within areas of infarction; cortex (28 +/- 20 compared with 109 +/- 23 mL/100 g/min contralateral to ischaemic focus, P = 0.001) and caudate (57 +/- 31 compared with 141 +/- 32 mL/100 g/min contralaterally, P = 0.005). The hypotensive challenge (mean arterial pressure reduced to 60 mmHg by increasing halothane concentration) did not compromise grey matter autoregulation in the contralateral hemisphere; CBF data were not significantly different at normotension and during hypotension. However, in the ipsilateral hemisphere, a significant volume of cortex adjacent to the infarct, which exhibited normal flow at normotension, became oligaemic during the hypotensive challenge (e.g. frontal parietal cortex 109 +/- 15% to 65 +/- 15% of cerebellar flow, P < 0.01). This resulted in a 2.5-fold increase in the volume of cortex which fell below 50% cerebellar flow (39 +/- 34 to 97 +/- 46 mm3, P = 0.003). Moderate hypotension induced a significant reduction in CBF in both ipsilateral and contralateral subcortical white matter (P < 0.01). In peri-infarct caudate tissue, CBF was not significantly affected by hypotension. In conclusion, a significant volume of histologically normal cortex within the middle cerebral artery territory was found to have essentially normal levels of CBF but impaired autoregulatory function at 24 h post-ischaemia.     

老年急性脑梗死患者血浆内皮素、心钠素的动态变化及其临床意义

目的:测定老年急性脑梗死患者血浆内皮素(ET)及心钠素(ANP)含量的动态变化,并探讨ET,ANP在老年急性脑梗死过程中的作用。方法:用放射免疫测定(RIA)法测定老年急性脑梗死组109例,冠心病组87例和对照组(健康志愿者)60例的血浆ET,ANP水平。结果:老年急性脑梗死患者发病后d2,15,30的血浆ET,ANP含量分别(141.3±10.7),(142.7±18.2);(123.6±4.3),(118.6±12.1);(85.4±15.7),(101.9±9.3)pg·mL~(-1),老年冠心病患者和对照组入组初血浆ET,ANP含量分别为(85.7±10.2),(103.9±9.3);(45.7±12.2),(67.4±9.5)pg·mL~(-1)。老年急性脑梗死患者和老年冠心病患者血浆ET,ANP水平较对照组明显升高(P<0.05),且随时间延长,老年急性脑梗死患者血浆ET,ANP含量均逐渐降低。结论:ET,ANP与老年急性脑梗死的发生、发展密切相关。     

慢性缺氧对大鼠肾功能和一氧化氮及内皮素的影响

目的　了解慢性缺氧对大鼠肾功能的影响 ,以及这种影响与一氧化氮 (NO)和内皮素 (ET)系统的关系。方法　制作慢性缺氧大鼠模型 ,测定血浆肌酐 (Scr)、尿素氮 (BUN)、尿NAG和肾组织NOS ,NO及ET - 1浓度 ,肾组织iNOS ,eNOS ,bNOS ,ETAR及ETBR的基因表达情况。结果　与正常大鼠相比 ,慢性缺氧大鼠血浆BUN及ET - 1浓度明显降低 (P均 <0 .0 5 ) ,Cr及NOS浓度无明显变化 (P >0 .0 5 ) ,尿NAG浓度明显升高 (P <0 .0 1) ,NO浓度明显降低 (P <0 .0 1)。肾脏匀浆中NOS含量轻度升高 (P >0 .0 5 ) ,NO含量明显升高 (P <0 .0 5 ) ,ET含量无明显变化 (P >0 .0 5 )。大鼠肾组织eNOSmRNA表达明显增加 ,iNOSmRNA表达明显减少 (P <0 .0 5 ) ,bNOSmRNA表达无明显变化 ;大鼠肾组织ETAR表达无明显增加 (P >0 .0 5 ) ,ETBRmRNA表达明显增加 (P <0 .0 5 )。结论　慢性缺氧可引起肾小管功能显著减退 ,可能与肾组织局部NO和ET系统表达改变有关。     

中药复方对实验性2型糖尿病肾病肾组织内皮素及其受体基因表达的影响

目的:观察中药复方、苯那普利对2型实验性糖尿病肾病(DN)肾组织内皮素及其受体基因表达的影响。揭示中药复方治疗2型DN机理。方法:建立2型链脲菌素DN模型,以中药复方、苯那普利干预。比较Upro,Glu,HbAlC变化,检测(RT-PCR)肾皮质ET-1,ETA-R的mRNA表达水平,分析肾组织病理学特征。结果:对Up-ro,Glu,HbAlC改善作用,中药复方、苯那普利与生理盐水差异有显著性;对Glu,HbAlC改善作用,中药复方与苯那普利差异有显著性;DN模型鼠肾皮质ET-1,ETA-R的mRNA表达水平增加,经中药复方、苯那普利干预,其表达过高水平下调,但仍高于正常对照。对肾小球系膜、系膜细胞增殖的影响,中药复方优于苯那普利。结论:ET参与DN发病机制;中药复方、苯那普利都能从ET及其受体基因转录水平上影响其表达量;中药复方不仅能减少DN尿白蛋白,而且还能改善血糖、糖化血红蛋白,抑制蛋白非酶糖化,抑制肾小球系膜、系膜细胞增殖。     

倒卵叶五加总皂苷对心肌缺血再灌注大鼠左心功能和血清一氧化氮及血浆内皮素的影响

目的　观察倒卵叶五加总皂苷对心肌缺血再灌注大鼠左心功能和血清一氧化氮 (NO)及血浆内皮素 (ET)的影响。方法　建立在体大鼠缺血再灌注损伤模型 ,用心功能分析系统测定左室心功能 ,用酶法测定血清NO水平及放免法测定血浆ET水平。实验分假手术组 (sham)、心肌缺血再灌注损伤组 (IR)和倒卵叶五加总皂苷 (SAOH ,10 0mg·Kg-1)治疗组。结果　IR组左室LVSP ,+dp/dtmax,-dp/dtmax,+dp/dtmax/IP明显下降 (P <0 .0 0 1) ,血清NO水平明显降低 ,而血浆ET水平则显著升高(P <0 .0 0 1) ;SAOH能够明显改善缺血再灌注损伤大鼠左心LVSP ,+dp/dtmax,-dp/dtmax,+dp/dtmax/IP ,提高血清NO ,降低血浆ET ,恢复NO/ET平衡 (P <0 .0 0 1)。结论　倒卵叶五加总皂苷能提高心肌缺血再灌注损伤大鼠血清NO水平和降低血浆ET含量 ,恢复NO/ET平衡 ,改善左心舒缩功能。     

Bosentan对培养乳鼠心肌细胞肥大的抑制作用

目的 :以内皮素 (ET 1)诱导培养的乳鼠心肌细胞肥大 ,观察内皮素受体拮抗剂bosentan对肥大心肌细胞的抑制作用。方法 :以胰酶消化法分离乳鼠心肌细胞 ,分 4组进行细胞培养。对照组常规培养 ,不加任何干预因素 ,其余 3组分别加入bosentan10 -8mol·L-1、ET 110 -10 mol·L-1、ET 110 -10 +bosentan10 -8mol·L-1,培养 72h后观察心肌细胞生长情况并用放免法测定培养液中ET 1和心钠素 (ANP)含量。结果 :各组ANP测定水平分别为 :对照组 6.4 6±0 .38μg·L-1,bosentan组 4 .87± 0 .5 6μg·L-1,ET 1组 13.60±1.12 μg·L-1,ET 1+bosentan组 9.4 2± 0 .5 8μg·L-1。镜下观察见ET 1刺激乳鼠心肌细胞肥大 ,加用bosentan能使心肌细胞肥大程度减轻。结论 :ET 1可刺激乳鼠心肌细胞肥大 ,bosentan可使心肌细胞分泌心钠素减少 ,抑制ET 1诱导的心肌细胞肥大作用。     

土鳖虫水提物对实验性高脂血症大鼠血管内皮和内皮素的影响

目的研究土鳖虫水提物对高脂血症大鼠血管内皮和内皮素 (ET)的影响。方法建立高脂血症大鼠模型 ,测定血浆ET的浓度 ,并应用内皮细胞铺片和免疫组化相结合的方法 ,在大鼠主动脉内皮细胞铺片上 ,计数内皮细胞和ET阳性细胞并定量分析ET的合成。结果实验第 80d ,与正常组比较 ,高脂组血浆ET显著增高 (P <0 .0 1) ;内皮铺片显示内皮细胞数量增多 ,排列紊乱 ,胞核大小和染色深浅不一 ,ET阳性细胞率显著升高 (P <0 .0 1)。土鳖虫中、高剂量组血浆ET水平和ET阳性细胞率显著降低 (P <0 .0 5～ 0 .0 1)。结论土鳖虫水提物能保护血管内皮 ,减少ET的合成与释放