L-arginine对局灶脑缺血脑细胞凋亡和微血管密度的影响

目的探讨NO合成底物左旋-精氨酸(L-Arg)对兔局灶脑缺血后血管再生和脑细胞凋亡的影响。方法兔局灶脑缺血后应用L-Arg,流式细胞仪定量分析细胞凋亡率的变化,CD34免疫组织化学测脑组织微血管密度(MVD),脑组织含水率评价脑水肿。结果与对照组比较,L-Arg组脑细胞凋亡率明显减少(8.72±2.62 vs 16.62±2.82,P<0.01),同时脑组织MVD却明显增加(1.21±0.43 vs 0.69±0.22,P<0.01)。结论外源性L-Arg可减少缺血后脑细胞凋亡并促进缺血后血管再生,对局灶脑缺血具有重要的神经保护作用。     

偏头痛和慢性紧张型头痛血浆精氨酸加压素、催产素及环核着酸含量测定

用放射免疫分析法测定了２８例偏头痛、１０例慢性紧张型头痛患者和１６例健康对照组血浆精氨酸加压素（ＡＶＰ）、催产素（ＯＴ）、环磷酸腺苷（ｃＡＭＰ）及环磷酸鸟苷（ｃＧＭＰ）含量。结果表明，偏头痛发作期ＡＶＰ含量下降、ｃＡＭＰ含量升高，偏头痛间歇期ｃＧＭＰ含量下降，血浆ＯＴ含量在发作期和间歇期均明显下降。慢性紧张型头痛患者血浆ＡＶＰ、ＯＴ、ｃＡＭＰ和ｃＧＭＰ与对照组比较均无显著性差异。结果提示，血浆ＡＶＰ和ＯＴ水平降低以及环核苷酸的代谢异常与偏头痛发病机制有关。     

杏仁内侧核微量注射AVP和AVPMcAb对兔ET性发热效应的影响

在杏仁内侧核微量注射精氨酸加压素（ＡＶＰ）和精氨酸加压素单克隆抗体（ＡＶＰＭｃ－Ａｂ），观察其对兔内毒素（ＥＴ）性发热效应的影响。结果表明，杏仁内侧核微量注射ＡＶＰ能明显抑制兔ＥＴ性发热效应，注射ＡＶＰＭｃＡｂ则能明显提高兔ＥＴ性发热效应；而将ＡＶＰ和ＡＶＰＭＣＡｂ注射到杏仁外侧核则对兔ＥＴ性发热效应无明显影响。提示：杏仁内侧核也是ＡＶＰ抗热作用的一个重要作用部位。     

Raised intracranial pressure,the syndrome of inappropriate antidiuretic hormone secretion,and arginine vasopressin in tuberculous meningitis

Intracranial pressure (ICP) monitored shortly after admission over a period of 1 h in 31 children with tuberculous meningitis (TBM) was significantly higher (median 22.5 mm Hg, range 8.4–50.9 mmHg) in 19 children with laboratory evidence of the syndrome of inappropriate antidiuretic hormone secretion (SIADH) than in 12 children without such evidence (median 16.2 mmHg, range 5.8–42.5 mmHg; P = 0.027). Neither plasma nor cerebrospinal fluid arginine vasopressin (AVP) was related to ICP (r = 0.33 and 0.13 respectively). Mean arterial pressure (MAP) was measured in 23 children and a moderate correlation was found with plasma AVP (r = 0.62; P = 0.0019). In TBM, plasma AVP may be secreted as a response to raised ICP in an effort to raise MAP and maintain cerebral perfusion pressure. In this setting excess fluid may be inappropriately retained, leading to hyponatremia and hypo-osmolemia.     

Bioavailability of 1-deamino-8-D-arginine vasopressin with an enzyme inhibitor (aprotinin) from the small intestine in healthy volunteers

Objective: The bioavailability of an aqueous solution of 1-deamino-8-D-arginine vasopressin (dDAVP), with and without an enzyme inhibitor, was studied in six healthy, male volunteers aged 19–34 years, followed for 8 h after each drug administration. Methods: For i.v. administration the subjects received 4 μg dDAVP. For intestinal administration 500 μg dDAVP was administered directly, in two separate sessions, in the first part of the duodenum via a triple-lumen channel tube. In one session a solution of isotonic polyethylene glycol (PEG) was given as a continuous enteral perfusion. In the other session a solution of PEG and aprotinin was administered enterally at the constant rate of 5 ml⋅min⁻¹ for 4 h. Plasma dDAVP was measured using a specific, sensitive radioimmunoassay and intestinal juice was collected for measurement of lipase, chymotrypsin and pH every 30 min for 5 h. Results: The intestinal chymotrypsin activity was decreased after perfusion of aprotinin while the lipase activity was not modified. After i.v. administration, the half-life of elimination of dDAVP was 1.56 h and plasma clearance 1.24 ml⋅min⋅kg⁻¹. The mean bioavailability after duodenal administration of dDAVP + aprotinin was 0.46% compared with 0.09% after duodenal administration of dDAVP alone. The bioavailability of dDAVP after direct duodenal administration of an aqueous solution was similar to that after swallowing a tablet in a previous study and increased 5 times when given together with a perfusion of an enzyme inhibitor. Received: 27 October 1995/Accepted in revised form: 26 February 1996     

卡维地洛对氧自由基诱导的内皮细胞内源性一氧化氮合酶抑制物代谢的影响

目的： 观察卡维地洛对氧自由基（OFR）培养的人脐静脉内皮细胞（HUVECs）二甲精氨酸-二甲赖氨酸水解酶 (DDAH)活性及表达的影响，以探讨卡维地洛对不对称二甲精氨酸（ADMA）代谢机制的影响。 方法： 采用改良的Jaffe法培养原代人脐静脉内皮细胞（HUVECs），取生长良好的3-6代HUVECs用于实验，分为①空白对照组：加DMEM培养液；②OFR组:加入OFR（0.01 mmol/L,0.1 mmol/L）；③OFR+卡维地洛组: 同时加入0.1 mmol/L OFR及卡维地洛（10 μmol/L）共孵24 h后, 检测上清液中一氧化氮（NO）、内皮素（ET）、ADMA含量、L-胍氨酸(L-cit)浓度及一氧化氮合酶（NOS）活性。用Western blotting法测定细胞裂解液中二甲基精氨酸-二甲基赖氨酸水解酶 (DDAH)的蛋白表达。 结果： OFR条件培养下,内皮细胞的代谢产物ADMA、ET的量均高于空白对照组,而NO的量及NOS的活性少于空白对照组;反映DDAH酶活性的L-cit浓度显著降低,且有浓度依赖性，而DDAH的表达无明显变化。卡维地洛干预组的ADMA、ET的量均低于OFR组，NOS活性及NO、L-cit浓度明显高于OFR组。 结论： OFR培养下，内皮损伤ADMA的增加与DDAH的活性减弱有关，而与DDAH的表达无关。卡维地洛通过增加DDAH活性促进ADMA代谢，使NOS活性增加，抑制OFR对内皮功能的损伤。     

L-精氨酸脂质体对慢性低O2高CO2肺血管L-精氨酸转运的影响

目的:探讨慢性低O₂高CO₂对大鼠肺动脉L-精氨酸(L-Arg)转运的影响与L-Arg脂质体的作用。方法:雄性SD大鼠40只,随机分成4组,正常对照组(NC)、单纯低O₂高CO₂组(HH)、低O₂高CO2加L-Arg组(HL)和低O₂高CO₂加L-Arg脂质体组(HP)。将肺动脉孵育,测定其对[³H]-L-Arg的摄取率,同时光镜下观察肺细小动脉显微结构的变化。结果:(1)肺动脉平均压(mPAP)、右心室(RV)和左心室加室间隔(LV+S)重量比值(RV/LV+S)比较:HH组明显高于NC组(P<0.05),HP组明显低于HH组及HL组(P<0.01);HL组与HH组相比无显著差别(P>0.05)。(2)肺动脉薄片对0.005mmol/L、0.01mmol/L、0.02mmol/L、0.05mmol/L、0.1mmol/L和0.2mmol/L[³H]-L-Arg摄取率比较:HH组明显低于NC组,HL组明显高于HH组;HP组显著高于HH组及HL组(P<0.01)。(3)光镜下HH组肺细小动脉内弹力板扭曲,中膜平滑肌细胞增生,管腔明显狭窄;HP组肺细小动脉内弹力板扭曲明显减轻,中膜平滑肌层变薄,管壁较均匀一致。结论:慢性低O₂高CO₂大鼠肺血管存在L-Arg的转运障碍,用脂质体作为载体可显著提高肺血管对L-Arg的跨膜转运,L-Arg脂质体治疗慢性肺动脉高压具有潜在临床应用价值。