生长激素对实验性梗阻性黄疸大鼠内毒素血症的防治

目的探讨生长激素对实验性梗阻性黄疸并发的内毒素血症及肠粘膜屏障损害的防治作用.方法建立梗阻性黄疸大鼠模型分为黄疸组(20只),生长激素治疗组20只,假手术组20只做为对照.治疗组每日皮下注射生长激素0.75?IU/kg,持续两周.第五周测定各组大鼠血内毒素值;电镜观察肠粘膜形态.结果生长激素治疗组内毒素值为(0.40±0.02)?EU/ml显著低于黄疸组的(0.77±0.03)?EU/ml,(t=6.237、P＜0.01).与假手术组无显著差异(P>0.05).电镜检查示黄疸组小肠上皮微绒毛破坏、细胞线粒体肿胀变性、内质网扩张、细胞核变性坏死.治疗组病变不明显,与假手术组相似.结论生长激素可保护梗阻性黄疸时肠粘膜屏障、降低内毒素血症的影响.     

生长激素减轻梗阻性黄疸时肠菌及内毒素移位的实验研究

目的　探讨生长激素减轻梗阻性黄疸时肠细菌及内毒素移位的作用及其机理。方法　将 60只大鼠随机均分为假手术组 (SO组 )、梗阻性黄疸组 (OJ组 )及生长激素组 (rhGH组 ) ,rhGH组每天皮下注射Saizen 0 .75u/kg ,SO组及OJ组则用等量生理盐水作对照。检测各组血内毒素水平 ,并取腹水、血及肠系膜淋巴结、肝脏、肾脏和脾脏作细菌培养 ,同时测定末段回肠之粘膜厚度及绒毛高度。结果　OJ组血内毒素值为 (0 .77± 0 .0 3 )u/ml,较rhGH组的 (0 .40±0 .0 2 )u/ml明显增高 (P <0 .0 1) ,rhGH组接近SO组的 (0 .3 3± 0 .0 3 )u/ml水平。OJ组细菌移位率为 5 8.8% ,较rhGH组 (10 .0 % )明显增高 (P<0 .0 1) ,rhGH组与SO组 (0 )比较 ,P>0 .0 5。rhGH组绒毛高度为 (2 3 7.5 2± 13 .65 ) μm ,较OJ组的(183 .3 9± 11.0 9) μm明显增高 (P<0 .0 1) ;rhGH组粘膜厚度为 (3 2 0 .81± 14 .3 4) μm ,较OJ组的 (2 5 5 .62± 16.5 8) μm增厚(P <0 .0 1)。结论　生长激素对肠粘膜屏障具有明显的保护作用 ,可有效减轻梗阻性黄疸时肠菌及内毒素的移位。     

梗阻性黄疸患者血浆可溶性P-选择素与内毒素的关系及其在凝血障碍中表达的意义

目的　探讨梗阻性黄疸 (OJ)患者血浆可溶性P 选择素 (sP selectin)与内毒素 (ET )的关系及其在凝血障碍中表达的意义。方法　将 3 3例胆总管结石并OJ患者和 3 1例急性胆囊炎并胆囊结石无OJ患者分为梗黄组和无黄组 ,2 5例健康人为健康组 ,3组患者测定血浆可溶性P 选择素、ET、D 二聚体 (D d)、纤维蛋白原 (FBG)、血清纤维蛋白原降解产物 (FDP)、活化部分凝血活酶时间 (KPTT)、凝血酶时间 (TT)。结果　梗黄组和无黄组可溶性P 选择素含量与ET含量有直线相关 (P <0 .0 1) ;在相同ET含量时 ,梗黄组的可溶性P 选择素 (3 5 1.90± 93 .83 ) μg/L高于无黄疸组[(2 3 3 .3 2± 82 .12 ) μg/L ,P <0 .0 1] ;梗黄组D d、FDP[(2 .14± 0 .3 7)mg/L、(15 .13± 0 .46)mg/L]高于无黄组 [(0 .76± 0 .2 7)mg/L、(6.2 1± 0 .3 9)mg/L] (P <0 .0 1) ;梗黄组可溶性P 选择素与D d、FDP之间均正相关 (P <0 .0 1)。结论　OJ是ET致血管内皮细胞损伤和血小板活化的敏感性因素 ,OJ患者表现为代偿性弥散性血管内凝血。     

梗阻性黄疸患者血浆可溶性P-选择素与内毒素、D-二聚体的关系及其意义

目的　研究梗阻性黄疸 (梗黄 )患者血浆可溶性P -选择素 (sP selectin ,sP s)与内毒素 (ET )及D -二聚体 (D d)的关系及其意义。方法　应用ELISA和鲎试剂比色法测定梗黄组、急性胆囊炎组和健康人组血浆sP s ,D d和ET含量。结果　健康人组血浆sP s含量为 (93 .43± 17.65 )ng/ml ,ET (0 .0 0 3 0± 0 .0 0 0 4)EU /ml ,D d(0 .3 9± 0 .2 1)mg/L ;急性胆囊炎组血浆sP s含量为 (2 3 3 .3 2± 82 .12 )ng/ml ,ET (0 .40 12± 0 .15 0 6)EU /ml ,D d(0 .76± 0 .2 7)mg/L ;梗黄组血浆sP s含量为 (3 5 1.90± 93 .83 )ng/ml ,ET(0 .3 814± 0 .14 3 0 )EU /ml ,D d(2 .14± 0 .3 7)mg/L。急性胆囊炎组和梗黄组sP s ,D d及ET均高于健康人组 (P <0 .0 1) ;梗黄组ET与急性胆囊组差异无显著性 ,但梗黄组sP s和D d较急性胆囊炎组高 (P <0 .0 1) ,梗黄组的以上二物质含量呈正相关性 (P <0 .0 1) ;急性胆囊炎组sP s与ET呈正相关性 (P <0 .0 1)。协方差分析表明 ,在相同ET含量时 ,梗黄组sP s高于急性胆囊炎组 (P <0 .0 1) ,且与D d有相关性 ,二者有相同变化趋势。结论　胆道梗阻是ET致血管内皮细胞损伤和血小板活化的敏感性因素 ,梗黄患者血液高凝状态与继发性纤溶反应处于动态平衡 ,提示动态监测血浆sP s和D d变化 ,     

梗阻性黄疸时脾切除对肠黏膜屏障影响的实验研究

目的 探讨脾脏在梗阻性黄疸(阻黄)中对肠黏膜屏障的作用及其机制.方法 50只Wistar大鼠随机分组,阻黄组开腹结扎胆总管;阻黄+脾切除组,同时切除脾脏.术后7d观察血浆内毒素水平的变化,用乳果糖/甘露醇(L/M)比值检测肠黏膜通透性;采用免疫组织化学、Western印迹检测末端回肠紧密连接蛋白闭锁小带-1(ZO-1)、闭锁蛋白的表达,并利用图像分析系统对Western印迹图像进行定量分析.结果 阻黄+脾切除后L/M的比值和血浆内毒素水平较阻黄组明显下降(均P=0.001).与阻黄组相比,阻黄+脾切除组的平均肠绒毛高度和隐窝深度有所上升(P=0.019、0.001).免疫组化显示术后7 d阻黄组ZO-1蛋白强阳性表达数(6/18)下降明显(P=0.021),阻黄+脾切除组(8/17)染色较阻黄组变化不大;闭锁蛋白的染色阻黄+脾切除组强阳性表达(7/17)高于阻黄组(4/18)(P=0.026).通过对Western印迹图像进行定量分析也得出同样的结论.结论 阻黄后肠黏膜通透性增加,肠黏膜屏障受损.同时切除脾脏,肠紧密连接蛋白成分的数量和分布改变,肠黏膜屏障的损害减轻.     

重组生长激素对实验性肝硬化肝细胞生长激素受体表达的调控作用

目的探讨重组生长激素对肝硬化肝细胞表达生长激素受体的调控作用。方法检测不同浓度的重组生长激素 (0、13 3、133 3、1333ng/ml)干预后大鼠肝硬化肝细胞生长激素受体的数量变化。结果培养后肝硬化肝细胞生长激素受体的数量 (10 4 /cell)分别为 0 73± 0 13、1 14± 0 17、1 2 3± 0 2 1、0 6 8± 0 10 (P <0 0 5 )。结论在一定浓度范围内重组生长激素对肝硬化肝细胞的生长激素受体具有正性调控作用     

人重组生长激素对梗阻性黄疸大鼠肠源性细菌/内毒素移位的影响

目的探讨人重组生长激素(rhGH)减轻梗阻性黄疸时肠源性细菌及内毒素移位的作用及机制。方法Wister大鼠42只分为3组假手术组(SO组)、胆总管结扎组(BDL组)及rhGH治疗组(rhGH组)。实验1周后检测各组肝功指标的变化及血浆内毒素水平,取肝、肾、肠系膜淋巴结等肠道外器官组织做细菌培养,电镜观察末端回肠黏膜变化。结果rhGH组多项肝功指标较BDL组明显改善,rhGH组血浆内毒素水平为(0·38±0·03)EU/ml,较BDL组的(0·65±0·04)EU/ml明显降低(P<0·01),与SO组的(0·30±0·02)EU/ml比较无显著差异(P>0·05)。BDL组肝、肾、肠系膜淋巴结中细菌移位率高于另两组,其中肠系膜淋巴结细菌移位率为64·29%,明显高于SO组及rhGH组(P<0·05),后两组之间各部位细菌检出率差别无显著性(P>0·05)。电镜显示BDL组肠黏膜上皮细胞坏死,细胞核固缩,线粒体肿胀变性,内质网明显扩张。rhGH组肠黏膜上皮改变较BDL组明显减轻,接近SO组所见。结论应用rhGH可保护梗阻性黄疸时小肠黏膜屏障功能,减少肠源性细菌/内毒素移位的发生。     

生长激素抗肝纤维化的作用及其机制

目的　探讨重组人生长激素 (rhGH)对肝硬化大鼠在肝功能、门静脉高压等方面的治疗作用及其可能的机制。方法　雄性SD大鼠建立肝硬化模型 ,随机分组 ,分别给予NS、rhGH (333ng/KgBW ,ip ,qd× 7d)处理。 结果　rhGH处理前后肝硬化肝组织GHR的配体结合容量 [fmol/mg ,(31± 4 )vs .(4 0± 7) ]及其mRNA量 (iOD ,pixel)均显著升高 (2 3± 3)vs.(4 2± 8) ;P <0 0 5 ,肝硬化大鼠血清白蛋白 (g/L )显著升高 (2 9± 4 )vs .(37± 7) ;P <0 0 5、ALT活性 (U/L)显著降低 (89± 15 ,6 9± 7;P <0 0 5 ) ,肝硬化肝组织丙二醛含量 (nmol/mg)显著降低 (18 7± 3 2 ,12 0± 2 2 ;P <0 0 5 )、超氧化物歧化酶活性 (U/mg)显著升高 (82 4± 10 8,10 2 9± 76 ;P <0 0 5 )、胶原纤维相对含量 (% )显著降低 (2 2 30± 3 86vs.14 70± 2 0 7;P <0 0 5 ) ,肝硬化大鼠的门静脉压 (cmH2 O)亦显著降低 (14 4± 2 0vs.9 3± 1 5 ;P <0 0 5 )。结论　药理剂量的rhGH能够促进肝硬化大鼠的白蛋白合成、改善肝细胞功能 ,有助于抑制肝组织纤维化、缓解门静脉压力。     

生长激素对短肠大鼠残留小肠形态及生长代谢的影响

目的　探讨单纯肠外营养 (PN)与添加生长激素 (GH)的PN对短肠大鼠残留小肠代偿的作用及作用机制。方法　将 2 0只短肠SD大鼠随机分成PN组及PN rhGH组。行细胞增殖核抗原 (PCNA)测定、原位末端标记 (TUNEL)染色及bcl 2、BaxmRNA测定。结果　PN组残留小肠粘膜明显萎缩 ,PN rhGH组肠萎缩显著改善。PCNA表达在PN组降低 [(8.37± 2 .2 3)个 /视野 ],PN rhGH组增高 [(19.2 8± 3.2 5 )个 /视野 ],差异有非常显著性 (P <0 .0 1)。凋亡指数在PN组增高 [(2 2 .32± 3.84)个 / 10 0细胞 ],PN rhGH组降低 [(8.0 6± 2 .2 3)个 / 10 0细胞 ],差异有非常显著性(P <0 .0 1)。bcl 2mRNA表达在PN组降低 (0 .2 0± 0 .0 3) ,在PN rhGH组增高 (0 .44± 0 .0 6 ) ,BaxmRNA表达则相反。结论　单纯PN使短肠大鼠残留小肠粘膜明显萎缩 ,rhGH通过促进肠粘膜上皮细胞增生与抑制肠粘膜上皮细胞凋亡 ,显著促进残留小肠的代偿适应。     

术前减黄治疗对梗阻性黄疸患者CA19-9的影响

目的 探讨术前减黄治疗对梗阻性黄疸患者CA19-9和TBil的影响,为梗阻性黄疸患者的鉴别诊断提供依据.方法 回顾性分析2005年7月至2008年7月成都军区总医院收治的32例梗阻性黄疸患者的临床资料.分析17例恶性胆道梗阻性黄疸患者(恶性梗阻组)和15例良性胆道梗阻性黄疸患者(良性梗阻组)通过PTBD进行减黄治疗前后的CAl9-9和TBil的变化情况.采用t检验分析数据.结果 经减黄治疗后,恶性梗阻组患者的TBil由(27l±74)μmol/L下降到(144±33)μmol/L,治疗前后比较差异有统计学意义(t=6.52,P<0.05);CA19-9由(277±114)U/ml下降到(264±98) U/ml,治疗前后比较差异无统计学意义(t=0.34,P>0.05).良性梗阻组患者的TBil和CA19-9均下降明显,分别由(245±67)μmol/L下降到(135±43)μmol/L和(239±103)U/ml下降到(117±84)U/ml,两种指标治疗前后比较差异有统计学意义(t=5.30,3.54,P<0.05).结论 对梗阻性黄疸患者术前进行减黄治疗,动态观察血清CA19-9变化情况,有利于梗阻性黄疸患者的鉴别诊断.     

Increased prevalence of radiological spinal deformities in adult patients with GH deficiency: influence of GH replacement therapy.

This cross-sectional study shows that a high number of untreated adult patients with GHD develop radiological vertebral deformities. Patients undergoing GH replacement treatment showed a significantly lower prevalence of vertebral deformities versus treated patients in the presence of similar BMD, as assessed by DXA. INTRODUCTION: In this cross-sectional study, we investigated whether the prevalence and degree of spinal deformities in adults with growth hormone deficiency (GHD) were related to the age of patients, degree of bone turnover, BMD, and recombinant human GH (rhGH) replacement therapy. MATERIALS AND METHODS: One hundred seven adult hypopituitary patients (67 males and 40 females; mean age, 47 years; range: 16-81 years) with severe GHD and 130 control subjects (39 males, 91 females; mean age: 58.9 years; range: 26-82 years) were evaluated for BMD (DXA) and vertebral deformities (quantitative morphometric analysis). At study entry, 65 patients were on replacement therapy with rhGH, whereas 42 patients had never undergone rhGH. RESULTS: Vertebral fractures were significantly more frequent in GHD patients versus control subjects (63.6% versus 37.7%; chi2 15.7; p < 0.001). The fracture prevalence, as well as the fracture number, was significantly higher in untreated versus treated patients (78.6% versus 53.8%; chi2: 6.7; p = 0.009), although the two groups of patients did not show any significant difference in median T score. In untreated GHD patients, the prevalence of vertebral deformities was correlated with T score (p = 0.002) and duration of disease (p = 0.003). In treated GHD patients, the prevalence of spinal deformities was correlated only with the timing of the beginning of rhGH replacement. CONCLUSIONS: This cross-sectional study reports high prevalence of vertebral radiological deformities in adult patients with untreated GHD. The replacement treatment of GHD leads to a significant decrease in fracture rate.     

Effects of GH in human muscle and fat

Skeletal muscle is the major constituent of lean body mass and a major determinant of energy expenditure both at rest and during physical activity. Growth hormone, in turn, influences muscle mass as well as energy expenditure. Growth hormone substitution in adults increases muscle mass by 5–10%, but part of the effect is attributed to rehydration rather than protein accretion. In addition, GH regulates substrate metabolism in muscle and in particular antagonizes insulin-stimulated glucose disposal. This effect is linked to increased free fatty acid (FFA) flux but the molecular mechanisms remain unclear. During fasting, GH-induced insulin resistance may be favorable by reducing the demand of gluconeogenesis from protein. But in the postprandial phase, GH exposure may compromise glucose tolerance via the same mechanisms. Understanding the mechanisms whereby GH antagonizes insulin-stimulated glucose disposal in muscle is an important future research field with implications for a variety of clinical conditions ranging from malnutrition to obesity and type 2 diabetes.     

Hypothalamic control of GH secretion: Pathophysiology and clinical implications

Summary GH is secreted episodically. Its pattern is regulated by the interplay of a releasing and a release-inhibiting hormone of hypothalamic origin.Modulation occurs by metabolic factors (glucose, free fatty acids, ketone bodies, amino acids). Altered GH secretion has been observed in states of metabolic derangement such as diabetes mellitus, malnutrition and obesity.Further modulation occurs by extrahypothalamic CNS structures. In man—but not in animals, including subhuman primates—sleep has an important effect on GH secretion. A defective GH secretory pattern has been found to occur in several states of sleep disturbance, such as sleep deprivation, narcolepsy, severe psychosocial derangement, the apallic syndrome. Other CNS influences on GH secretion are related to stress, emotional changes and psychiatric disturbances.The exact mechanisms by which most of these influences are relayed to the GH secretory apparatus of the hypothalamus remain yet to be investigated.Original work of the author was supported by Deutsche Forschungsgemeinschaft.     

GH/IGF-1与骨质疏松的研究进展

骨质疏松症是由多种原因引起的一种系统性疾病,其机制极其复杂。生长激素(GH)和胰岛素样生长因子1(IGF-1)在骨的代谢过程中作用显著,其体内水平的变化与骨量及骨密度的维持密切相关。GH/IGF-1对于治疗骨质疏松有潜在的应用价值及广阔前景。本文就GH/IGF-1与骨质疏松的关系及相应作用机制作一综述。     

Two cases of recurrent brain tumor during GH replacement therapy]

Two cases of patients with recurrent brain tumor are presented. Each of them received growth hormone (GH) replacement therapy for growth failure secondary to cranial irradiation. The first case is that of a 10-year-old girl who was treated with a combination of surgical resection, radiotherapy and chemotherapy for cerebellar medulloblastoma at 1 y.o. At the age of 9, 10 month after the beginning of GH replacement therapy, she complained of headache. This was due to shunt malfunction when CSF cytology was class V. It revealed that there was recurrence of medulloblastoma. The second case is that of a 14-year-old girl who was treated with a combination of surgical resection, radiotherapy and chemotherapy for suprasellar germinoma at the age of 10. This tumor completely disappeared after these procedures. For her growth failure, we started GH replacement therapy and after 1 year, she complained of lt. leg pain due to tibial and pelvic bone metastasis. In medical literature, we found 15 recurrent brain tumors during GH replacement therapy. These include our 2 cases, and 9 cases in which there was recurrence within 1 year. Recently, receptors for some somatomedins have been found in brain tumors. Although these numbers are too small for us to arrive at conclusions, we think it is possible that there are some mechanisms connecting GH replacement therapy and recurrence of certain brain tumors.     

无肝状态下大鼠体内GH与FT4水平的变化

目的研究肝移植术无肝期前后生长激素(GH)、游离甲状腺素T4(FT4)水平变化。方法SPF级雄性SD大鼠20只,乙醚麻醉后,行右侧颈深静脉切开,置入1.0号硅胶管。于麻醉后(无肝期前)、肝门阻断30min(无肝期30min)、60min(无肝期60min)等时间点,从右颈深静脉采血1ml,采用放射免疫法检测三个时相点GH、FT4血清水平的变化。结果GH血清水平无肝期30和60min均显著高于无肝期前(P<0.01),FT4血清水平无肝期30和60min均显著高于无肝期前(P<0.01),无肝期30min与60min相比差异有统计学意义(P<0.05)。结论无肝期大鼠GH、FT4血清水平均显著升高,这可能影响麻醉药物的肝外代谢。     

Fracture incidence in GH-deficient patients on complete hormone replacement including GH.

Fracture risk in GHD patients is not definitely established. Studying fracture incidence in 832 patients on GH therapy and 2581 matched population controls, we recorded a doubled fracture risk in CO GHD women, but a significantly lower fracture risk in AO GHD men. INTRODUCTION: The objective of this study was to evaluate fracture incidence in patients with confirmed growth hormone deficiency (GHD) on replacement therapy (including growth hormone [GH]) compared with population controls, while also taking potential confounders and effect modifiers into account. MATERIALS AND METHODS: Eight hundred thirty-two patients with GHD and 2581 matched population controls answered a questionnaire about fractures and other background information. Incidence rate ratio (IRR) and 95% CI for first fracture were estimated. The median time on GH therapy for childhood onset (CO) GHD men and women was 15 and 12 yr, respectively, and 6 and 5 yr for adult onset (AO) GHD men and women, respectively. RESULTS: A more than doubled risk (IRR, 2.29; 95% CI, 1.23-4.28) for nonosteoporotic fractures was recorded in women with CO GHD, whereas no risk increase was observed among CO GHD men (IRR, 0.61) and AO GHD women (IRR, 1.08). A significantly decreased incidence of fractures (IRR, 0.54; 95% CI, 0.34-0.86) was recorded in AO GHD men. CONCLUSIONS: Increased fracture risk in CO GHD women can most likely be explained by interaction between oral estrogen and the GH-IGF-I axis. The adequate substitution rate of testosterone (90%) and GH (94%) may have resulted in significantly lower fracture risk in AO GHD men.