Somatostatin sst5 inhibition of receptor mediated regeneration of rat aortic vascular smooth muscle cells

1. The aim of the present study was to determine the effect of somatostatin (SRIF) on mitogen-induced regeneration of rat aortic vascular smooth muscle cells (VSMC) and for comparison Chinese hamster ovary (CHO)-K1 cells expressing human recombinant sst₅ receptors (CHOsst₅), following partial denudation of a confluent cell monolayer. Regeneration was assessed by measuring areas of recovery into the denuded area and by counting total cell numbers.
2. In VSMC, SRIF (0.1 nM–1 μM) had no effect on the basal levels of regeneration but caused a concentration-dependent inhibition (pIC₅₀ 8.0–8.6) of the stimulated regeneration induced by sub-maximal concentrations of basic fibroblast growth factor (bFGF, 10 ng ml⁻¹), platelet-derived growth factor-BB (PDGF, 5 ng ml⁻¹) or endothelin-1 (ET-1, 100 nM). SRIF (pIC₅₀ 8.8) also inhibited bFGF-induced regeneration of CHOsst₅ cells.
3. In VSMC, the inhibitory action of SRIF on the regeneration induced by bFGF (10 ng ml⁻¹) was due to an anti-proliferative effect, rather than an effect on cell migration, as SRIF (0.1 nM–1 μM) abolished bFGF-induced increases in total cell numbers. The bFGF-induced increase in cell numbers was also abolished by actinomycin D (0.1 μg ml⁻¹).
4. The sst₅ receptor-selective agonist, L-362,855 (pIC₅₀ 10.5), was about 100 times more potent than SRIF at inhibiting bFGF-induced regeneration of both VSMC and CHOsst₅ cells whilst the sst₂ receptor-selective agonist, BIM-23027 (pIC₅₀ 6.8), was approximately 20 times weaker than SRIF.
5. The sst₅ receptor antagonist, BIM-23056 (100 nM), antagonized SRIF-induced inhibition of bFGF-induced regeneration in both VSMC and CHOsst₅ cells (estimated pK_B values 8.8 and 8.3, respectively).
6. SRIF-induced inhibition of bFGF-induced regeneration of VSMC and CHOsst₅ cells was abolished by pretreating cells with pertussis toxin (100 ng ml⁻¹) for 20 h.
7. These findings suggest that SRIF-induced inhibition of the proliferation of rat aortic VSMC is mediated via activation of receptors which are similar to human sst₅ receptors. Furthermore this inhibitory effect is transduced via pertussis toxin-sensitive G_i/G_o proteins.

     

Somatostatin receptor scintigraphy during treatment with lanreotide in patients with neuroendocrine tumors

To investigate possible changes in somatostatin receptor expression during treatment with high dose lanreotide, eight patients with neuroendocrine tumors were investigated by [¹¹¹In-DTPA-D-Phe¹]-octreotide scintigraphy before and during treatment. The spleen-to-background ratio decreased in all patients, whereas tumor-to-background ratio revealed a heterogeneous pattern with an average increase of 50% (−79% to +1,087%). This finding indicates that lanreotide treatment may influence the binding of radioactively labeled somatostatin to the spleen, while changes in the binding to functioning somatostatin receptors in tumor cells are more complex and not clearly related to treatment.     

慢性癫痫大鼠脑组织生长抑素受体功能的变化

探讨癫痫发病的生化机制。方法用１２５Ｉ－ＳＯＭ作为配基,采用放射性配基受体结合分析法,对戊四氮诱导的慢性癫痫大鼠海马生长抑素（ＳＯＭ）受体功能进行了测定。结果慢性癫痫大鼠及对照组海马ＳＯＭ受体的Ｂｍａｘ值分别为２４６．０±１８．２ｐｍｏｌ／ｇ蛋白质及２２０．０±１５．３ｐｍｏｌ／ｇ蛋白质,Ｋｄ值分别为４．１９±０．３４ｎｍｏｌ／Ｌ及３．８９±０．２２ｎｍｏｌ／Ｌ。常用的抗痫药卡马西平（ＣＢＺ）、丙戌酸钠（ＶＰＡ）及钙桔抗剂尼莫地平（ＮＩＭ）能降低受体的亲和力,而苯妥因钠（ＰＨＴ）则无影响。结论ＳＯＭ受体活性增高在癫痫发病中起着重要作用,常用抗痫药的抗痫活性可能与其降低ＳＯＭ受体活性有关。     

Insulin-like growth factor-1 (IGF-1)-induced inhibition of growth hormone secretion is associated with sleep suppression

The hypothalamic growth hormone (GH)-releasing hormone (GHRH) promotes non-rapid eye movement sleep (NREMS). Insulin-like growth factor-1 (IGF-1) acts as a negative feedback in the somatotropic axis inhibiting GHRH and stimulating somatostatin. To determine whether this feedback alters sleep, rats and rabbits were injected intracerebroventricularly (i.c.v.) with IGF-1 (5.0 and 0.25 microgram, respectively) and the sleep-wake activity was studied. Compared to baseline (i.c.v. injection of physiological saline), IGF-1 elicited prompt suppressions in both NREMS and rapid eye movement sleep (REMS) in postinjection hour 1 in rats and rabbits. The intensity of NREMS (characterized by the slow wave activity of the EEG by means of fast-Fourier analysis) was significantly enhanced 7 to 11 h postinjection in rats. Plasma GH concentrations were measured in 30-min samples after i.c.v. IGF-1 injection in rats and a significant suppression of GH secretion was observed 30 min postinjection. The simultaneous inhibition of the somatotropic axis and sleep raises the possibility that the sleep alterations also result from an IGF-1-induced suppression of GHRH. The late increases in NREMS intensity are attributed to metabolic actions of IGF-1 or to a release of GHRH from the IGF-1-induced inhibition.     

生长抑素治疗食管静脉曲张破裂出血30例疗效分析

目的：观察生长抑素治疗食管静脉曲张破裂出血的疗效。方法：治疗组30例用生长抑素静滴维持，对照组30例用垂体后叶素及硝酸甘油静滴维持。结果：治疗组48h内止血27例，止血率为90％，对照组48h止血16例，止血率为53．3％。两组相比止血率有非常显著性差异（P＜0．01）。结论：生长抑素治疗食管静脉曲张破裂出血，具有止血速度快，止血率高及无明显副作用等优点，疗效优于垂体后叶素。     

大肠癌和癌旁粘膜中胃泌素,生长抑素变化的研究

临床观察大肠癌和癌旁粘膜中胃泌素，生长抑素及其分泌细胞的变化 ，探讨病人体内胃泌素、ＳＳ变化的原因和意义。方法：采用放射免疫法测定２６例大肠癌病人肿瘤和癌旁粘膜中胃泌素，生长抑素水平，并对其分泌细胞行免疫细胞化学观察。     

生长抑素在肠梗阻治疗中的作用

目的探讨生长抑素在肠梗阻治疗中的应用效果。方法将我科78例各型肠梗阻,随机分为常规治疗对照组40例及实验组38例,实验组常规治疗基础上加用生长抑素(6 mg,iv,gtt,qd),对比两组的疗效。结果实验组临床症状较对照组明显改善,腹胀、腹痛减轻,胃肠引流量减少,治疗后肛门开始排气时间明显的缩短。结论在常规治疗基础上加用生长抑素静脉滴注能改善肠梗阻患者临床症状,适于各型肠梗阻的治疗,但不能减少其必要手术治疗病例的比例。     

大肠癌组织中生长抑素与cyclins、CDKs表达的相关性研究

目的研究大肠癌组织中生长抑素(SS)的表达与细胞周期调控因子———细胞周期素(cyc lins)、细胞周期依赖性蛋白激酶(CDKs)表达的相关性,了解SS对大肠癌细胞增殖的具体调控机制,从而进一步完善大肠癌的发病机制,为激素依赖性大肠癌的内分泌联合基因治疗提供理论依据。方法随机选择79例大肠癌(结肠癌、直肠癌)患者的手术切除标本,用免疫组织化学方法中的SP法检测SS、cyc linD1、cyc linE、cyc linA、cyc linB1、cdc2、CDK2、CDK4的表达情况。结果Cyc linE、CDK2在大肠癌组织SS高表达组的表达低于低表达组(P<0.05)。Cyc linD1、cyc linA、cy-c linB1、cdc2、CDK4在大肠癌组织SS高、中、低表达组三组间相比较差异无统计学意义(P>0.05)。结论在大肠癌组织中,SS表达的水平越高,cyc linE、CDK2的阳性表达率越低,因此,SS对大肠癌细胞周期的调控可能是:SS抑制大肠癌细胞cyc linE、CDK2基因的表达,使cyc linE-CDK2复合物的水平降低,进而抑制细胞从G1期到S期的转化,使进入S期的细胞数减少,以诱导细胞周期阻滞,抑制细胞增殖。     

胃肠激素检测在小于胎龄儿变化中临床意义

应用放射免疫法对68例小于胎龄儿(其中早产36例;足月32例)生后喂奶前及第7日空腹血中生长抑素(soma-tostatin,SS)、胃动素(motilin,MOT)、胃泌素(gastrin,Gas)浓度进行测定,并以30例足月新生儿作为对照组。结果小于胎龄儿组生后喂奶前及第7日空腹血浆胃动素、胃泌素均明显低于对照组,而生长抑素浓度明显高于对照组.并且与胎龄、开始喂养时间及当日进奶等因素相关。结论小于胎龄儿消化道机能适应胃肠道营养,在严密观察下应用合理的喂养方式早日开始胃肠道营养,将能促进小于胎龄儿胃肠道的发育和成熟。     

生长抑素治疗开胸术后乳糜胸的疗效观察

目的探讨生长抑素对开胸术后乳糜胸的治疗价值。方法将开胸术后乳糜胸患者分为两组。治疗组行生长抑素 保守治疗;对照组行保守治疗。对比两组患者胸腔闭式引流每日减少量与治愈时间。结果两组胸腔闭式引流每日减少量与治愈时间对比差异有统计学意义(P<0.05)。结论生长抑素对开胸术后乳糜胸有良好疗效。