5-HTP induced diarrhea as a carcinoid syndrome model in mice?

Summary— Serotonin (5-HT) is present in the gastrointestinal tract and is probably one of the compounds responsible for diarrhea in patients presenting with carcinoid syndrome. Intraperitoneal administration of L-5-hydroxytryptophan (L-5-HTP) at doses of 25 to 100 mg/kg dramatically increase defecation in mice. In this new paradigm, counting fecal boli deposited is simple and the appraised or inhibition of diarrhea induced by ip 25 mg/kg of L-5-HTP is very clear, with a good reproducibility of scores. L-5-HTP needs to be metabolized into 5-HT to be active; benserazide, an inhibitor of decarboxylase, antagonized the diarrhea induced by 5-HT. Among the 5-HT antagonists used in interaction with 5-HT, only those of the 5-HT₃ type (ondansetron, granisetron, tropisetron) and, to a lesser extent 5-HT₂ type (ritanserin), decreased the diarrhea induced by 5-HTP. The 5-HT₄ receptor agonists from the benzamide family (metoclopramide and zacopride) increased defecation in mice but the effect failed to reach statistical significance.     

5-羟色胺对巨核系造血的影响

5-羟色胺（5-HT）是一种细胞生长因子，主要结合到细胞表面的5-HT1受体、5-HT2受体，通过Ras、MAPK通路促进多种细胞的增殖。在巨核系造血的早期，5-HT通过5-HT2B受体促进造血干细胞及巨核系祖细胞增殖和分化，其具体机制尚未十分清楚；在巨核系造血晚期，5-HT与5-HT2A受体结合促进一氧化氮合成，可能对血小板的释放有一定的影响。另外，5-HT能够对抗血小板α颗粒内容物血小板反应蛋白-1（TPS-1）所引起的巨核细胞凋亡，协同另一内容物血小板源性生长因子（PDGF）引起的巨核细胞增殖，因此5-HT可能是血小板反馈调节中比较重要的物质。本文就5HT及其受体、5HT是细胞生长因子、5HT促进细胞增殖的途径及5HT对巨核系祖细胞的影响进行了综述。     

5-羟色胺1/2受体拮抗剂米安色林对大鼠睡眠呼吸暂停的影响

目的 中枢5-羟色胺(5-HT)及其受体在呼吸调控中发挥着重要作用.呼吸调控不稳定可以导致不规则的呼吸以及呼吸暂停的发生.本研究的目的 在于探讨5-HT1/2受体在大鼠睡眠呼吸暂停中的作用.方法 成年SD大鼠10只,手术埋置脑电、肌电电极和微注射套管.通过体描箱和多导生理仪,监测大鼠脑电、肌电和呼吸.通过微量泵,向第四脑室匀速泵入5-HT1/2受体的拮抗剂米安色林(mianserin)(100 μmol/L)40 μl,观察大鼠给药前后呼吸暂停的变化.结果大鼠呈现两种呼吸暂停的类型:自发呼吸暂停(spontaneous apnea)和叹息后呼吸暂停(post-sigh apnea).中枢微注射5-HT1/2受体拮抗剂米安色林减小了慢速眼球运动睡眠(non-rapid eye movements,NREM) 和快速眼球运动睡眠(REM)期的叹息后睡眠呼吸暂停(P<0.05),而对NREM 和 REM 期的自发呼吸暂停无影响(P>0.05),对总睡眠呼吸暂停指数也无显著影响(P>0.05).在睡眠结构方面,米安色林对睡眠效率及睡眠结构无显著影响(P>0.05).结论 5-HT 和5-HT1/2受体在呼吸调控网络中扮演重要角色,并与大鼠中枢型呼吸暂停的发生密切相关.5-HT1/2受体的不同亚型既有兴奋性受体,又有抑制性受体.米安色林对5-HT1/2受体的双向调节作用可能导致呼吸暂停减轻.     

高脂饮食对大鼠脑微血管内皮细胞HIF-1α及Claudin-5表达的影响

目的研究高脂饮食对大鼠脑微血管内皮细胞HIF-1α及Claudin-5表达的影响,初步探讨高脂毒性对大鼠脑微血管的损伤机制。方法 (1)40只SD大鼠随机分为高脂组与正常对照组,每组20只,分别予以高脂饲料和普通饲料喂养8周。(2)测定各组大鼠基础、第4周、第8周时体重及代谢指标变化。(3)8周时处死各组大鼠,免疫组化检测各组大鼠脑微血管内皮细胞上HIF-1α及Claudin-5蛋白表达情况,伊文氏蓝(EB)染色检测血-脑屏障(BBB)的通透性。结果 (1)高脂组大鼠体重由基础值(165.00±12.100)g增加至8周时的(401.30±66.827)g;对照组大鼠体重由基础值(163.00±10.100)g增加至8周时的(321.10±18.300)g,两组比较差异有统计学意义(P<0.05)。(2)高脂组大鼠空腹血总胆固醇(TC)由基础值(1.576±0.138 9)mmol/L升高为8周时的(2.032±0.365 0)mmol/L,甘油三酯(TG)由基础值(0.601±0.117 2)mmol/L升高至8周时的(2.679±1.087 6)mmol/L,且显著高于相应时间点正常对照组(P<0.05)。(3)8周时高脂组大鼠脑皮质微血管内皮细胞上,HIF-1α表达强于正常对照组(P<0.05),Claudin-5表达呈弱阳性,正常对照组大鼠Claudin-5呈强阳性表达(P<0.05)。(4)8周时高脂组大鼠EB含量较正常对照组升高,差异有统计学意义(P<0.05)。结论高脂可通过上调HIF-1α蛋白的表达水平使紧密连接蛋白Claudin-5的表达下降,导致微血管病变及增加BBB的通透性。     

Pharmacological analysis of the cardiac effects of 5-HT and some 5-HT receptor agonists in the pithed rat

Summary— A pharmacological analysis of the effects of 5-HT on heart rate has been performed in the pithed rat. 5-HT induced a dose-dependent increase in heart rate whereas 5-HT, receptor agonists — 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), 5-methoxy-N,N-dimethyl-tryptamine (5-MeODMT), 5-methoxy 3-(1,2,3,6-tetrahydro-4-piridinyl) 1H indole (RU 24969) and 1-(m-trifluoromethylphenyl)-piperazine (TFMPP) — failed to increase heart rate. The increase in heart rate induced by the selective 5-HT₂ receptor agonist 1-(2,5-dimethoxy-4-iodo-phenyl)-2-aminopropane (DOI) was not significant. The dose-response curve to 5-HT for its tachycardic effects was shifted two-fold to the right by ketanserin and LY 53857 and nine-fold to the right by methiothepin. The effects of high doses of 5-HT (higher than 100 μg/kg iv) were antagonized by methiothepin, (-)propranolol, 2-{2-[4(O-methoxyphenyl)-piperazine-1-yl]-ethyl}4,4-dimethyl-1,3 (2H-4H) isoquinoline-dione (AR-C 239) and by pretreatment with reserpine. The 5-HT₁ receptor antagonists, pindolol and spiroxatrine, the 5-HT₃ receptor antagonist MDL 72222 and the α₂-adrenoceptor blocking agent idazoxan failed to antagonize the tachycardia induced by 5-HT. It is concluded that in the pithed rat, the tachycardia induced by 5-HT remained unexplained (implication of 5-HT₂ receptors probably different from the classical vascular 5-HT₂ receptor, or implication of 5-HT_1C receptors?). Moreover, at high doses (higher than 100 μ/kg iv), 5-HT may increase heart rate by releasing catecholamines.     

C5-siRNA对乳鼠心肌细胞缺氧复氧损伤的保护作用

目的研究C5-siRNA对乳鼠心肌细胞缺氧复氧损伤的保护作用。方法用原代单层培养的心肌细胞分为4组:正常对照组(C组)、H/R组、H/R+C5-siRNA组、H/R+空载体病毒组。其中后三组均经历2小时缺氧和4小时复氧,H/R+C5-siRNA组及H/R+空载体病毒组在缺氧前2小时分别给予C5-siRNA及空载体病毒。用CKK-8快速比色法检测心肌细胞存活情况(OD值)及用Western Blot法及RT-PCR法检测C5。结果心肌细胞存活情况H/R+C5-siR-NA组显著高于H/R组及H/R+空载体病毒组,而C5表达量H/R+C5-siRNA组显著低于H/R组及H/R+空载体病毒组。结论 C5-siRNA对乳鼠心肌细胞缺氧复氧损伤具有保护作用,其机理可能与降低C5表达有关。     

蛋白酶体抑制剂MG-132作用下失神经骨骼肌myf-5的表达

背景:MG-132是蛋白酶体抑制剂的一种,有报道显示其对失神经骨骼肌萎缩有延缓作用.目的:进一步验证蛋白酶体抑制剂MG-132对大鼠骨骼肌成肌调节因子myf-5基因表达的影响.方法:SD大鼠随机被分成3组,空白对照组不切断坐骨神经,仅做假手术,去神经组和去神经MG-132干预组切断坐骨神经1 cm以上,制作失神经骨骼肌动物模型,去神经MG-132干预组肌肉内注射MG-132.分别于去神经第2,7,28 d处死大鼠.用反转录聚合酶链式反应技术检测myf-5 mRNA表达情况,Western-blot检测myf-5蛋白表达的变化.结果及结论:在去神经支配后第2,7,28天,与空白对照组比较,去神经组、去神经MG-132干预组myf-5mRNA和蛋白质均表达上调(P<0.01);去神经MG-132干预组myf-5mRNA和蛋白表达较去神经组均明显上调(P<0.01).结果提示蛋白酶体抑制剂MG-132可以通过抑制泛素-蛋白酶体途径来上调myf-5的表达,从而起到延缓骨骼肌萎缩的作用.     

5-HT 2 Serotonin Receptor on Blood Platelet of Migraine Patients

Several lines of evidence have previously suggested that platelets might play a primary or secondary role in migraine pathogenesis, and that in addition serotonin receptors on human platelets might be involved in those processes. By using [3H]-spiperone as a radioligand and ketanserin to determine the non-specific binding, the numbers of 5-HT2 serotonin receptors on platelet membrane obtained from normal healthy and migraine subjects were determined. We found a significant decrease (p < 0.02) in the maximal receptor numbers (Bmax) on platelet membrane of migraine patients (Bmax = 33.01 +/- 5.57 fmol/mg protein) when compared to the normal healthy group (Bmax = 86.59 +/- 9.09 fmol/mg protein) whereas the dissociation equilibrium constant (Kd) values (2.47 +/- 0.44 nM and 3.41 +/- 0.95 nM for the normal and migraine subjects, respectively) remained unchanged. The platelet response showed a higher degree of aggregability in migraine subjects, whereas the platelet counts were the same. This finding implies that serotonin receptors on the platelet may reflect some aspect of the pathogenesis of migraine headache.