妊娠肝内胆汁淤积症患者血清一氧化氮和内皮素的变化及意义

目的：探讨妊娠肝内胆汁淤积症（ICP）患者外周静脉血清、新生儿脐静脉血清中一氧化氮（NO）、内皮素（ET）、丙二醛（MDA）和超氧化物歧化酶（SOD）含量的变化及在ICP发病中的作用。方法：以ICP组28例为研究组，测定其外周静脉血清及新生儿脐静脉血清中的NO、ET、MDA和SOD，以年龄相近的24例正常孕妇作为对照组。结果：ICP患者的MDA和ET含量较正常晚期妊娠显著增高（P＜0．01），ICP患者的NO和SOD含量与对照组相比无显著性差异（P＞0．05）。母血清中NO、ET、MDA含量均较新生儿脐静脉血清中的含量高，差异有显著性（P＜0．01）。结论：妊娠期体内氧化和抗氧化失衡及ET水平的增高可能与ICP的发生、发展有关。     

益气复脉汤对脑缺血再灌注损伤大鼠ET及CGRP影响的实验研究

目的：观察益气复脉汤对脑缺血再灌注模型大鼠血浆内皮素（ET）和降钙素基因相关肽（CGRP）含量变化的影响，探讨大鼠脑缺血再灌注损伤的中医药治疗方法。方法：采用线栓法制备大鼠右侧大脑中动脉脑缺血再灌注损伤模型，分别用益气复脉汤高、低剂量组、尼莫地平水溶液予以治疗，然后采用放射免疫法检测血清ET和CGRP含量。结果：模型组脑缺血再灌注大鼠血浆ET含量明显增高，而CGRP下降，治疗后ET值比对照组下降明显（P〈0．01），CGRP值比对照组增高明显（P〈0．05）。结论：益气复脉汤通过降低ET和增高CGRP，能够对脑缺血再灌注损伤脑起保护作用，其疗效优于尼莫地平。     

舒胆合剂防治阻塞性黄疸肾功能障碍的作用机制

目的 探讨在阻塞性黄疸(OJ)时舒胆合剂的抗内毒素及对肾功能的保护作用。方法 SD大鼠胆总管结扎后分3组，每组10只，分别用2mL舒胆合剂、乳果糖液(每100mL含乳果糖67g)、生理盐水灌胃，连用9d。假手术组10只，用2mL生理盐水灌胃。观察内毒素、血和肾组织中内皮素(ET)、一氧化氮(NO)的含量、一氧化氮合酶(NOS)活性及肾功能的变化。结果 舒胆合剂组与乳果糖组血内毒素、血和肾组织ET水平较生理盐水组明显降低，血和肾组织N0、NOS活性、内生肌酐清除率、肾皮质血流量较生理盐水组明显升高。结论 在OJ时，中药舒胆合剂有抗内毒素作用，并通过减少体内内毒素水平来降低体内ET水平，升高N0水平起到保护肾功能的作用。     

Two-step hard acid deprotection/cleavage procedure for solid phase peptide synthesis

A new two-step deprotection/cleavage procedure for t-butoxycarbonyl (Boc) based solid phase peptide synthesis is reported. First the protective groups are removed from 4-(oxymethyl)-phenylacetamidomethyl (PAM) resin attached peptide with the weak hard acid, trimethylsilyl bromide-thioanisole/trifluoroacetic acid (TFA). In the second step, the peptide is cleaved from the resin with a stronger hard acid such as trimethylsilvl trifluoromethanesulfonate in TFA or with HF. The method is also shown to deformylate Nⁱⁿ-formyltryptophan moiety efficiently. The usefulness of this procedure for practical solid phase peptide synthesis is demonstrated by comparison with other deprotection methods in the synthesis of urotensin II and human endothelin.     

新生儿缺氧缺血性脑病血浆内皮素与肺功能的关系

目的 :探讨内皮素 (ET)、在新生儿缺氧缺血性脑病 (HIE)中的作用及与肺功能关系。方法 :将 4 2例 HIE患儿按病情分为轻、中、重三组 ,各组均在入院后第 2天采用婴儿体描箱进行潮气呼吸分析、有效气道阻力及功能残气量等肺功能测定同时用放射免疫法测定血浆 ET水平。结果 :中、重度 HIE组血浆 ET水平均高于轻度组及对照组 ;中、重度HIE组肺功能测定提示 TPTEF/ TE、VPEF/ VE、PEF的下降。重度 HIE组潮气量下降 ,有效气道阻力增高。结论 :血浆ET水平增高与 HIE病情的严重程度相一致 ,肺功能检测指标可以解释血浆 ET水平的增高在新生儿中、重度 HIE发生肺动脉高压及急性肺损伤中起的作用 ,对 HIE临床治疗有一定的指导作用     

3,6-(二甲氨基)-二苯骈碘杂六环葡萄糖酸盐对AGEP引起的大鼠主动脉平滑肌细胞增殖及牛主动脉内皮细胞内皮素和一氧化氮改变的影响

目的 :观察 3 ,6 (二甲氨基 ) 二苯骈碘杂六环葡萄糖酸盐对AGEP引起的大鼠主动脉平滑肌细胞增殖及牛主动脉内皮细胞内皮素和一氧化氮改变的影响。方法 :采用牛血清白蛋白 (BSA)与不同浓度葡萄糖 (0 ,2 0 ,5 0 ,80mmol·L-1)体外孵育制备糖基化终产物 (AGEP) ,应用 [3 H] TdR掺入法和MTT比色法观察I-93对重度糖化的AGEP诱导的大鼠主动脉平滑肌细胞 (ASMC)增殖的影响 ;应用放射免疫技术及Greiss法观察I -93对AGEP引起的牛主动脉内皮细胞 (BAEC)释放内皮素 1(ET 1)和一氧化氮 (NO)的影响。结果 :I-93 10 -7～ 10 -5mol·L-1能明显抑制AGEP引起的ASMC增殖 ,其 [3 H] TdR掺入量和MTT比色法的最大抑制率分别为79 .4%和 44 .2 %。随AGEP糖浓度的增加 (2 0～ 80mmol·L-1) ,BAEC培养液中ET 1含量亦逐渐上升 [(4 93± 63 )～ (779± 10 5 )ng·L-1] ,I -93 10 -7～ 10 -5mol·L-1能明显抑制重度糖化的AGEP促进ET 1释放的作用 ;I -93对AGEP灭活NO的作用有剂量依赖性抑制效应。结论 :I -93有抑制ASMC增殖的作用 ;对AGEP诱导的BAEC释放ET 1和NO间平衡失调有调节作用 ,在防治阻塞性血管疾病方面I -93具有潜在的应用价值     

Changes in blood pressure and vasoactive hormones during volume expansion in stable patients on chronic haemodialysis

Summary: We studied changes in blood pressure (BP) and plasma hormones (atrial natriuretic peptide [ANP], brain natriuretic peptide [BNP], endothelin [ET], angiotensin [AII] and renin [PRA]) in four stable haemodialysis patients 48 h after a routine dialysis (basal stat), after volume expansion (4–7% above dry bodyweight) for 4 days then 48 h later following ultrafiltration. Blood pressure rose and plasma AII and PRA values fell with volume expansion and returned to baseline at the end of the study. Endothelin values were unchanged. Plasma ANP and BNP rose similarly in three patients and returned to near baseline levels after ultrafiltration. Sustained volume expansion over 4 days in dialysis patients is associated with an increase in BP, a marked elevation in plasma ANP and BNP but without change in ET.     

内皮素和降钙素基因相关肽与梗阻性黄疸大鼠门脉压力的关系

目的　通过测定梗阻性黄疸大鼠门静脉血中内皮素和降钙素基因相关肽浓度 ,探讨内皮素和降钙素基因相关肽在梗阻性黄疸鼠门脉压力升高中的作用。方法　建立大鼠梗阻性黄疸模型 ,采用放射免疫法测定门静脉血中内皮素和降钙素基因相关肽的浓度。结果　内皮素在胆道结扎后各时相均明显升高 (P<0 .0 5 ) ,3天达峰值 (186.99± 3 6.0 3 pg/ m l) ,降钙素基因相关肽在胆道结扎后第 1天无明显变化 (2 13 .11± 3 5 .3 8pg/ m l vs 180 .14± 3 0 .66pg/ ml) ,3天后明显升高 ,并与对照组相差明显 (P<0 .0 5 )。梗阻性黄疸组大鼠门脉压力在各时相组均比对照组明显升高 (P<0 .0 5 )但未形成门脉高压。内皮素抗血清治疗可降低内皮素浓度和升高的门静脉压力。结论　梗阻性黄疸时内皮素和降钙素基因相关肽浓度均升高 ,失去内皮素和降钙素基因相关肽的正常平衡并伴有门脉压力的升高     

随意皮瓣术后内皮素变化及其受体阻滞剂对皮瓣微循环的影响

目的:探讨随意皮瓣术后内皮素(ET)水平变化及内皮素受体阻滞剂BQ-123(A选择性)对随意皮瓣微循环的影响.方法:SD大鼠背部肉膜下形成随意皮瓣,测皮瓣组织ET的变化趋势.分用药组(BQ-123组)和对照组(生理盐水组),测皮瓣存活率,取材进行HE染色光镜检查,使用激光多谱勒血流仪测量皮瓣血运情况.结果:皮瓣术后ET水平急剧上升,24 h内维持较高水平.术后第10天,用药组皮瓣的存活率显著高于对照组.HE染色光镜检查见用药组组织损害较对照组小.激光多谱勒测量发现用药组较对照组激光多谱勒血流量相对值(LDF)下降少,恢复快.结论:皮瓣术后ET水平急剧上升,并维持较高水平,内皮素受体阻滞剂BQ-123(ETA高度选择性)可以阻断ET作用途径,有利于改善皮瓣微循环.     

Site-specific biotinylation

We have developed an expeditious method for the incorporation of the biotinylaminocaproyl moiety on the ε-amino group of a lysine residue within a peptide chain in a site-specific manner. Using t-Boc chemistry for the solid phase synthesis approach and a base labile, acid stable protecting group (Fmoc-) for the ε-amino group of the target lysine, we prepared fully protected resin bound peptides which are site-specifically biotinylated. Following HF cleavage, the uniquely biotinylated peptides were obtained in a high degree of purity. Using this approach, a number of biotinylaminocaproyllysyl derivatives of a monocyclic Endothelin-1 analog were prepared. Synthesis of selected bicyclic analogs of high affinity monocycles led to the preparation of the bicyclic [Nle⁷]ET-1 analog containing ε-biotinylaminocaproyllysine at position-9. This peptide, with K_d= 0.08 nM, has 1000-fold higher affinity for the ET_A receptor than the commercially available N_α-biotinylated Endothelin-1. The general utility of this biotinylation methodology was demonstrated by the synthesis of a site-specifically biotinylated PTH analog which contained several side chain functionalized amino acid residues in its sequence. The synthetic method reported here is convergent in that it allows the facile variation of the length of the spacer and also offers the potential to introduce in a site specific manner other groups such as affinity labels and fluorescent tags.