重组人生长激素长疗程治疗特发性矮小症疗效观察

目的探讨基因重组人生长激素(recombinant human growth hormone,rhGH)对特发性矮小症(idiopathic shortstature,ISS)儿童长疗程治疗的疗效。方法 60例ISS患儿(男性21例,女性39例),每晚皮下注射rhGH 0.15～0.18IU/(kg.d),疗程1～3年。评价治疗前后身高、生长速度、身高标准差计数(SDS)、骨龄、预测成年身高变化及副作用。结果①rhGH治疗1～3年期间,60例患儿生长速率由治疗前的每年(4.51±0.46)cm分别提高到(10.97±2.53)、(8.11±1.54)cm和(7.13±2.07)cm;身高SDS由治疗前(-2.60±0.57)增至(-1.62±0.64)、(-1.29±0.89)及(-0.12±0.45);预测成人身高由治疗前(151.62±8.46)cm分别增加为(157.33±8.50)、(160.72±10.31)cm和(165.81±7.46)cm(P<0.05)。②不同青春期开始治疗的疗效比较,TannerⅠ、Ⅱ、Ⅲ期患儿生长速率相接近,明显高于Ⅳ期。③骨龄增长低于身高年龄增长(P<0.05),而与年龄增长相一致(P>0.05)。结论长疗程rhGH治疗对ISS有明显的促生长效应,增加了预测成年身高;青春期前、青春早中期开始治疗的疗效优于青春晚期;长疗程的rhGH治疗未引起骨龄和青春期提前。     

Efficacy of Subcutaneous Administration of Gonadotropin-releasing Hormone Agonist on Idiopathic Central Precocious Puberty

In order to assess the feasibility of subcutaneous administration of Triptorelin with 6-week intervals for the suppression of pituitary-gonadal axis and changes of clinical signs in girls with idiopathic central precocious puberty (ICPP), 46 girls with ICPP were treated with GnRHa. Triptorelin (Decapeptyl, 3.75 mg) was administered subcutaneously (SC) at 6-weeks intervals or intramuscularly (IM) at 4-weeks intervals randomly for more than 12 months consecutively. During GnRHa therapy, clinical parameters and laboratory data, including height, weight, pubertal stage, bone age, uterine volume and ovarian size, serum levels of luteinizing hormone (LH), follicle stimulating hormone (FSH) and estradiol (E2), were monitored and analyzed. It was found that both treatment regimes led to regression of precocious puberty and reversal of secondary sexual characteristics. Breast developments regressed. Uterine volume was decreased after treatment, but there was no statistically significant difference. Mean ovarian volume did not change significantly during treatment. The height velocity was decreased significantly from 6.3±1.4 cm/year to 5.8±1.2 cm/year in group SC and 6.7±1.3 cm/year to 5.4±1.0 cm/year in group IM, respectively. The rate of bone maturation was reduced significantly during treatment. The ratio of deltaBA/deltaCA was 1.2±0.2 or 1.3±0.3 at the onset of therapy and decreased significantly after the treatment to 0.7±0.2 or 0.9±0.1, respectively. The predicted adult height was increased significantly and progressively during therapy. The levels of serum LH, FSH and E2 returned to the prepubertal condition. No significant side effects of therapy were noted. The most common side effect during SC treatment was that a non-irritating, 1 cm in diameter mass was palpated at the site of subcutaneous injection in the abdominal wall of patients, which disappeared after 6-12 weeks. Two girls had minimal withdrawal vaginal bleeding episodes after the first injection. It was concluded that both IM and SC triptorelin administrations were clinically effective. They induce profound suppression of hypothalamic-pituitary-gonadal axis while stabilizing height velocity, slowing bone maturation and increasing predicted adult height. These results suggest that subcutaneous injection of triptorelin in 6-weeks intervals at a dosage of 3.75 mg be a safe and acceptable regimen for ICPP     

Prader-Labhart-Willi syndrome: auxological response to a conventional dose of growth hormone in patients with classical growth hormone deficiency

The aim of the study was to evaluate the effect of growth hormone (GH) (14 IU/m2/week) on height, body mass index and predicted adult height in children with Prader-Labhart-Willi (PLWS) syndrome and GH deficiency. - By auxological criteria GH deficiency was suspected in 10 patients (age: 7-16 years). In 9 patients two GH provocative testings and MR imaging of the pituitary were performed. IGF-I measurements, bone age determinations, body mass index (BMI), height standard deviation score, height velocity -SDS and predicted adult height (PAH) were determined before and during GH treatment. Nine patients could be followed for up to 2 years, 3 patients for 4 years and 2 patients for 5 years of GH treatment. - Predicted adult height could be calculated in all after 1 year of treatment and was on average 11.6 cm below target height (-17.6 to +2.5 cm). GH treatment in a conventional dose (14 IU/m2/week) in daily subcutaneous injections was performed. Height SDS improved from -3.47 to -2.27 after 2 years of treatment, height velocity SDS from -1.74 to +2.65 after 1 year and remained +1.78 after 2 years. PAH increased on average by 5.1 cm. BMI was unchanged during 2 years. Bone age development was appropriate with +2.13 years after 2 years. In 2 patients who were treated with GH for up to 5 years and in 1 who was treated up to 4 years, the positive effect on height SDS and height velocity SDS persisted. - In conclusion GH treatment in a conventional dose (14 IU/m2/week) in PLWS patients with GH deficiency is effective over a period of 2 years in regard to height development and predicted adult height but ony limited in regard to changes in BMI.     

Turner综合征矮身材的治疗

This study was aimed to examine the growth-promoting effects of recombinant human growth hormone (r-hGH) and low dose of thyroid hormone on short stature in girls with Turner syndrome. 8 girls with Turner syndrome, at the chronological age of 8.5-14.5 years (12.3 +/- 2.1 years) and bone age of 8.3-12.7 years (9.8 +/- 1.7 years) were observed. The maximum serum GH levels in 3 patients out of 5 with provocative testing available were > or = 10 ng/ml (10.0, 10.0 and 15.52 ng/ml, respectively), and in the other 2 of the 5 patients were < 10 ng/ml (9.3 and 9.5 ng/ml). Thyroid function including T3, T4 and TSH were measured in 5 patients. The TSH in one patient was slightly higher; the T3, T4 and TSH in other patients were normal. All patients were treated with r-hGH 1.0 IU/(kg.wk) and thyroideum 15 mg/d for 6-36 months. The results showed that the growth rate after treatment was remarkably higher than that before treatment (2.2 +/- 1.1 cm/yr). The growth rates in the first 6 month, the first year, the second year and the third year were 7.9 +/- 1.6 cm/yr, 7.5 +/- 1.2 cm/yr, 6.9 +/- 0.2 cm/yr and 5.0 +/- 0.2 cm/yr, respectively. Height standard deviation score (HSDS) increased 1.3 +/- 1.1 SD, compared with that pretreatment. The annual bone age growth rate after treatment was 0.6 +/- 0.2 yr/yr (0.43-0.8 yr/yr). These data indicated that r-hGH and low dose of thyroid hormone had remarkable effects of growth-promoting in the girls with Turner syndrome.     

The Northern Ireland experience of growth hormone therapy for short stature

In 1967 the first patient in Northern Ireland commenced growth hormone treatment for short stature. By the end of December 1988 a total of 89 patients had been treated. Thirty-two had idiopathic isolated growth hormone deficiency, an incidence of 1.5 new cases per year (in a population of 1.5 million with approximately 30,000 births per year). Since 1967 the mean age at starting treatment has fallen from 18 years to 10 years and the height standard deviation score has fallen from -4.7 +/- 0.6 to -3.4 +/- 0.3. The group with classical growth hormone deficiency (maximum GH less than 7 mU/l during insulin-induced hypoglycaemia) had a greater increase in height velocity over the first year of treatment, 3.8 +/- 0.4 cm, than those with a partial deficiency (maximum growth hormone 7.1 - 20 mU/l), 1.9 +/- 0.4 cm. All pre-pubertal children responded with a rise in the height velocity standard deviation score from -1.8 +/- 0.3 before treatment to +3.5 +/- 0.4 over the first year of treatment. 58% of the adult males and 25% of adult females have attained an adult height within the normal range (3rd centile or above). There have been three deaths, one each from Fanconi's aplastic anaemia which predated growth hormone treatment, an accidental fire injury and a relapsing craniopharyngioma. There have been no deaths from Creutzfeldt-Jakob disease. Growth hormone therapy is safe and effective, but continues to be commenced late in terms both of age and height standard deviation score.     

来曲唑治疗纤维性骨营养不良综合征女性患儿外周性性早熟疗效观察

目的: 探讨应用第三代芳香化酶抑制剂来曲唑治疗纤维性骨营养不良综合征（MAS）女性患儿外周性性早熟的疗效及安全性。方法: 选取2012年3月至2017年6月在上海交通大学医学院附属瑞金医院儿科就诊的MAS女性患儿21例。患儿反复阴道出血、乳房增大同时伴或不伴咖啡牛奶色斑或骨纤维发育不良,黄体生成素（LH）和卵泡刺激素（FSH）水平低下,排除先天性肾上腺皮质增生症、分泌雌激素的肿瘤及外源性雌激素摄入所致等情况。给予来曲唑0.5~2 mg·m^-2·d^-1治疗,疗程6~12个月,观察患儿乳房分期变化、阴道出血次数、性激素水平、肝功能、骨龄变化、子宫卵巢容积变化及有无不良事件发生。结果: 经过来曲唑治疗后,患儿骨龄与时序年龄比值减小（1.23±0.30降至1.11±0.18,P < 0.01）;预测成年身高从（156.2±5.9）cm增加至（158.4±2.1）cm（P < 0.05）;阴道出血次数减少,雌二醇水平下降,睾酮未见明显升高;子宫未见明显增大,也未发生卵巢扭转及肝酶升高等不良反应。结论: 来曲唑治疗MAS相关的外周性性早熟可延缓骨龄进展,减少阴道出血的频率,未观察到肝功能受损等不良反应。     

125例Turner征核型和自然身高的分析

的 :分析Turner征的核型和自然身高情况 ,以供临床早期诊断。方法 :1982～ 2 0 0 0年以来 ,通过染色体G显带、C显带、N显带、高分辨等技术 ,确诊为Turner征者共 12 5例 ,分析其初诊时的核型和身高。结果 :本组核型主要为 4 5 ,XO(33 6 % ) ;4 5 ,XO 4 6 ,X ,i(Xq) (16 % ) ;4 5 ,XO 4 6 ,XX(10 4 % ) ;4 6 ,X ,i(Xq) (8.8% ) ;4 5 ,XO 4 6 ,XY(8 8% )。身高落后在 14岁时达到最大 ,平均成年身高为 (137 8± 9.9)cm ,比相应正常标准矮 2 1.1cm。 4 5 ,XO个体比非 4 5 ,XO个体矮。结论 :生长受损可能主要发生在 14岁以前 ,提示应提早诊断 ,及早治疗。     

Use of growth hormone in non-growth hormone deficient children

The easy availability of growth hormone (GH) in the Indian market has led to its increased use in the management of short stature. However, the therapy is expensive for most families. The possible benefits of such a therapy have to be carefully weighed against the cost and adverse effects. We discuss the drawbacks of relying on data based on predicted height to evaluate the benefits of GH therapy reported in the literature. It is the final adult height which is the true indicator of the efficacy of GH therapy. The only clear indications for GH therapy are short stature associated with GH deficiency and Turner syndrome. Classifying short stature may not be of much help in deciding the utility of GH therapy and the use of auxological criteria alone will increase the burden on society. At present, the use of GH in idiopathic short stature is not indicated in routine clinical practice.     

来曲唑改善青春期特发性身材矮小症男性患儿成年身高的疗效评价

目的: 观察和评估芳香化酶抑制剂来曲唑治疗已进入青春期的特发性身材矮小症（ISS）男性患儿的疗效和安全性。方法: 收集2004—2017年在中山大学附属第一医院儿科内分泌专科门诊就诊,身高低于同年龄、同性别平均水平2个标准差以下并已经进入青春期的ISS男性患儿75例,按所选择的治疗方案分为来曲唑组、促性腺激素释放激素类似物（GnRHa）组和无干预组。其中,来曲唑组28例,应用来曲唑治疗,剂量为1.5~2.0 mg·m^-2·d^-1（最大剂量不超过2.5 mg/d）,1次/d顿服,同时给予螺内酯1~2 mg·kg^-1·d^-1,分次口服;GnRHa组30例,采用GnRHa治疗,首剂3.75 mg,以后按60~100 μg/kg每28 d注射1次;无干预组17例,无任何干预措施。比较各组身高增长速度（HV）、骨龄差值/时序年龄差值比值（ΔBA/ΔCA）及成年身高,同时观察来曲唑治疗的不良反应。结果: 来曲唑组在治疗过程中HV维持在相对较高水平,而GnRHa组治疗的前半年HV稍低于来曲唑组,半年后HV回落明显,显著低于来曲唑组（P < 0.05）。在骨龄控制方面,来曲唑组第一年和次年的ΔBA/ΔCA逐渐下降,分别为0.67±0.09和0.50±0.15;而GnRHa组则分别为0.59±0.16和0.44±0.13,均低于来曲唑组且差异有统计学意义（t=2.78和2.20,均P < 0.05）。来曲唑及GnRHa治疗后患儿成年身高分别为（170±4）cm和（170±6）cm,差异无统计学意义（P>0.05）,均高于无干预组患儿成年身高（162±4）cm（均P < 0.01）。来曲唑治疗6个月后,患儿睾丸容积及血睾酮增加。39.2%（11/28）的患儿出现高雄激素临床表现,82.1%（23/28）的患儿治疗过程中出现血高密度脂蛋白（HDL）降低,终止治疗后高雄激素表现消失,血睾酮及血HDL恢复正常。血三酰甘油、血低密度脂蛋白（LDL）、空腹胰岛素、血糖及胰岛素抵抗指数在治疗过程中无显著变化（均P>0.05）,未见肝功能异常、关节或肌肉疼痛、脊柱侧弯发生或加重者。结论: 对于青春期ISS男性患儿,长疗程来曲唑可有效延缓骨龄增长,同时不会使HV减速,从而达到有效改善成年身高的远期效果,且未见明显不良反应。     

Research on treatment of female idiopathic precocious puberty with combined traditional Chinese medicine and megestrol acetate

Objective: To find effective therapeutic approach for treating true idiopathic precocious puberty suitable to our national condition and different from gonadotrophin releasing hormone analogue.Methods: One hundred and six girls with idiopathic precocious puberty were divided into 3 groups. The 51 girls in the TCM-WM group were treated with Chinese herbal medicine combined with megestrol acetate (MA), 35 girls in the MA group treated with megestrol acetate alone, and 20 girls were taken as control group and given no treatment at all. Luteinizing hormone releasing hormone (LHRH) stimulating test were performed before and after treatment, and the size of the uterus and ovary, linear growth rate, X-ray bone age measurement and final height prediction were also observed simultaneously.Results: After treated with TCM-WM for 2.7 years in average, the luteinizing hormone (LH) peak value of LHRH stimulating test was reduced from 48.5 ± 5.2 IU/L to 12. 2 ± 1.3 IU/L, size of uterus and ovary decreased, secondary sexual characteristics regressed, the bone age difference/chronological age difference value (ΔBA/ΔCA) reduced from 1.35 ± 0.09 to 0.65 ± 0.05 and predictive final height increased from 153.3 ± 0.5 cm to 158.5 ± 0.6 cm.Conclusion: TCM-WM therapy could not only modulate the function of hypothalamic-pituitary-ovarian axis and the development of internal genitalia, but also could decelerate skeletal growth, delay skeletal maturation, and thereby prevent premature epiphyseal fusion and increase the final height of patients.     

贵阳市婴幼儿和青少年发育调查研究──Ⅳ:737名儿童成年身高预测研究分析

７３７名儿童成年身高预测表明：男性预测成年身高为１６８～１７０ｃｍ，女性为１５８～１６０ｃｍ；儿童发育提前或迟后都将影响成年身高；１３岁～１５岁月经初潮的女性成年身高明显高于其他年龄月经初潮的女性。     

GnRHa治疗中枢性男性性早熟的疗效分析

目的观察促性腺激素释放激素类似物（GnRHa）对中枢性男性性早熟（CPP）男孩的第二性征、身高、骨龄、体重指数、预测身高等指标的影响。方法对28例中枢性男性性早熟男孩给予GnRHa治疗,辅以有氧运动,对治疗前后的第二性征、身高、骨龄、体重指数、预测身高、终身高等指标进行评价分析。结果治疗前身高（HT）（147．5±5．9）cm,预测身高（PAH）（164．8±5．4）cm,治疗1年后HT（154．3±6．0）cm,PAH（168．8±6．2）em,2年后HT（158．1±4．8）cm,PAH（172．2±6．5）cm;性激素水平（T、E2、LH、FSH）回至青春前期,睾丸有所缩小;骨龄受抑,骨龄的标准差分值（HtSDSBA）由原来的（-1．6±0．6）增至1年后的（-1．1±0．7）（P〈0．01）;2年后增至（-0．7±0．7）（P〈0．01）。结论GnRHa能有效改善中枢性男性性早熟的终身高,且无明显不良反应。     

Medical Research Council of Canada therapeutic trial of human growth hormone: first 5 years of therapy.

The Medical Research Council of Canada has initiated human growth hormone (hGH) therapy in 151 patients with documented complete hGH deficiency that was idiopathic in 76% of cases, secondary to craniopharyngioma (organic) in 17% and of varied cause in 7%. Approximately 50% of the patients with idiopathic disease had isolated hGH deficiency; during therapy thyroid deficiency developed in five patients and cortisol deficiency in three. A similar increase in mean height velocity occurred in the first treatment phase for patients less than 12 years old (0.93 plus or minus 0.30 cm/mo) and those 12 years and older (0.86 plus or minus 0.29 cm/mo). Although subsequent courses of hGH therapy yielded significantly diminished response in both age groups, this diminution was not progressive: the height velocity of the younger patients returned to 0.82 plus or minus 0.26 cm/ml in the fifth therapy phase. The mean height velocity attained at the optimal dosage (0.20 to 0.29 units/kg three times per week) for each age group did not differ significantly. Despite therapy being carried out for only 6 months of the year, normal increment ratios for height age and bone age against chronologic age were observed in the patients with idiopathic disease. In only four patients did treatment failure occur, and three of these were more than 20 years old. The addition of fluoxymesterone (10 mg/d) to the hGH therapeutic regimen (15 units/wk), when diminished response to hGH alone became evident, promoted an enhanced growth response in 9 of 11 older patients. These data indicate that age of the patient and dosage of hGH, but not diagnostic category, were important influences on the response to therapy. Younger patients responded best and maintained a higher mean growth velocity than older patients during intermittent hGH therapy     

小儿特发性矮小症治疗中重组人生长激素应用的价值分析

目的探讨分析小儿特发性矮小症治疗中重组人生长激素应用的价值。方法回顾性分析该院于2012年11月—2013年12月收治的100例小儿特发性矮小症患者的病历资料,随机的分为对照组和治疗组,对照组和治疗组各50例。对照组患者采取正常的营养治疗,并对患者补充钙和赖氨肌醇维生素B12。治疗组患者在对照组常规营养治疗的基础上采取重组人生长激素治疗,对比分析两组患者治疗前后生长速度、骨龄以及身高等情况。结果治疗组治疗之后的生长速度为（13.2±2.4）cm/年,其差值明显高于对照组的（6.68±1.21）cm/年,对照组和治疗组患者治疗之后的生长速度、骨龄以及骨龄对应的身高标准差分值等进行比较,差异有统计学意义（P〈0.05）。结论小儿特发性矮小症治疗中重组人生长激素应用价值较高,不仅仅将患儿的生长速度增加,同时又是一种安全有效的治疗方法,有着一定的可行性和安全性,值得临床推广。     

重组hGH再次治疗生长激素缺乏侏儒的疗效

本文报告用重组hGH治疗特发性生长激素缺乏侏儒第二年的疗效。剂量和方法同第一年,身高生长速率由1.9±1.0cm/年增加至9.2±1.2cm/年,比第一年治疗生长速率10.7±0.5cm/年为低(P<0.05)。结果显示,剂量以每周0.7IU/kg分7次皮下注射比每周0.5IU/kg分3次肌肉注射疗效更好。9例患者用药后8例T_4降低,无临床甲状腺功能低下症状,2例有抗hGH抗体,但不妨碍生长,无其他副作用。     

重组人生长激素治疗不同骨龄生长激素缺乏症患儿的疗效观察

目的 基因重组人生长激素(rhGH)治疗矮小症的有效性已得到广泛验证，开始治疗时的骨龄，治疗的疗程、剂量等都可影响rhGH治疗的疗效，本文主要探讨rhGH治疗生长激素缺乏症(GHD)患儿的疗效，观察开始治疗时的骨龄对rhGH疗效的影响。 方法 选择2012年8月—2017年8月安徽省立医院儿科收治的青春期前GHD患儿共42例，分骨龄小于8岁组(＜8岁组)23例，骨龄大于等于8岁组(≥8岁组)19例，均接受rhGH治疗6个月，剂量为0.1 IU/(kg·d)。比较2组治疗前后的身高、生长速率(GV)、身高的标准差分值(HtSDS)等；比较治疗后2组间的△GV、△HtSDS。组内治疗前后比较采用配对t检验；2组间比较采用独立样本t检验；两变量之间相关性采用Pearson相关分析。 结果 6个月后，2组的身高、GV、HtSDS均较治疗前明显增高(均P＜0.05)；＜8岁组的△GV、△HtSDS分别为(6.17±1.44)cm/年、0.50±0.13，≥8岁组的△GV、△HtSDS分别为(5.28±0.69)cm/年、0.23±0.17，2组间比较差异有统计学意义(均P＜0.05)；2组治疗6个月后的△GV、△HtSDS与开始治疗时的年龄、骨龄呈负相关(均P＜0.01)。 结论 rhGH治疗GHD患儿疗效肯定，开始治疗时的骨龄越小，疗效越好。      

胎儿心脏右心房主要结构增龄变化观测

目的观测不同胎龄心脏右心房结构、大小及变化规律。方法40例胎心标本按胎龄分为4组,对右心房内主要结构进行观测比较,用统计学方法处理数据。结果各结构总体均数(cm)如下:上腔静脉内径0.42±0.17cm、冠状窦口直径0.21±0.08cm、右房室口直径0.75±0.27cm、右房壁厚度0.08±0.03cm、卵圆孔高度和宽度0.18±0.79cm和0.32±0.11cm、第一房室间隔高度和宽度0.52±0.21cm和0.21±0.08cm。下腔静脉瓣出现率为100%,Chair′s网占7.5%。冠状窦口瓣膜出现率为97.6%。筛状瓣膜占冠状窦口瓣膜的5%。结论上腔静脉内径、右房室口直径、第一房间隔高度和宽度随胎龄的增长而增加。冠状窦口直径、右房壁厚度、卵圆孔高度和宽度变化不规则。     

生长激素治疗特发性矮小儿童随访至接近成年终身高的治疗效果分析

目的 评价用生长激素治疗的特发性矮小（idiopathic short status,ISS）年长儿随访至接近成年终身高的治疗效果,并分析相关影响因素。方法 随访曾予生长激素治疗、目前已停药并达接近成年终身高的ISS患者。主要评价指标为接近成年终身高标准差积分（near-adult height standard deviation scores,NAHtSDS）与遗传靶身高（target height,TH）,也叫父母中位身高（mid-parent height,MPH）,标准差积分（standard deviation scores,SDS）的差值,即△HtSDS,并分析相关影响因素。结果 生长激素治疗初始HtSDS男女分别为-3.31,-2.86。接近成年终身高HtSDS分别为-1.98,-1.39。男女患儿接近成年终身高SDS与用药初始SDS相比,差异有统计学意义（P=0.000）。以遗传靶身高HtSDS为标准,采用非劣效检验分析接近成年终身高与遗传靶身高接近程度,提示ISS男性患儿接近成年终身高低于遗传靶身高,女性患儿接近成年终身高不劣于遗传靶身高。55.7%（59/106例）ISS男性患儿、71.4%（50/70例）ISS女性患儿其接近成年终身高HtSDS>-2 SD,即达到正常、非矮小身高。这部分人群,男性患儿和女性患儿在<1年和 ≥ 1年的疗程内,其接近成年终身高与遗传靶身高HtSDS相比,均具有非劣效性。采用多重线性回归,以△HtSDS为因变量,分析性别、用药初始年龄、用药初始HtSDS、用药初始骨龄、疗程对△HtSDS的影响。性别、用药初始HtSDS、疗程对△HtSDS的影响差异有统计学意义（P值分别为0.005,0.000,0.027）。结论 本研究ISS年长儿,应用生长激素治疗,大部分可达到正常人群身高。女性患儿、用药初始HtSDS高、长疗程,有助于其达到或接近遗传靶身高。     

司坦唑醇对雌激素受抑的青春期大鼠生长板 软骨细胞生长和成熟的影响

 【目的】 探讨司坦唑醇(ST)对离体培养的促性腺激素释放激素拟似物(GnRHa)处理后青春期大鼠生长板软骨细胞的增殖和分化的影响&#65377; 【方法】 将6只经GnRHa 处理后雌鼠的原代软骨细胞分为时效组(观察ST干预时限的影响)&#65380;量效组(观察ST干预剂量的影响)&#65377;时效组和量效组中,又分为ST干预时效组,对照时效组;ST干预量效组,对照量效组&#65377;通过噻唑兰比色分析法(MTT)法和免疫组化法检测软骨细胞核增殖细胞核抗原(PCNA)&#65380;胞浆中Ⅱ型胶原&#65380;Ⅹ型胶原的表达&#65377;【结果】 (1)对MTT&#65380;PCNA的影响改变 ①时效组:ST 作用后1 天2参数已有显著升高(P < 0.05),并与基值比较,第2 天时达峰(P < 0.001)&#65377;但第4下降至与0 天时比较无差异(P > 0.05)&#65377;②量效组:低浓度的ST无显著促增殖效应(P > 0.05),而浓度增加至10-9 mol/L时促增殖效应显现(P < 0.01),进一步加大ST 浓度至10-5 mol/L,促增殖效应又开始减弱&#65377;(2)对软骨细胞胶原Ⅱ&#65380;Ⅹ合成的影响: ①时效组:ST作用3 d后胶原Ⅱ的表达明显高于对照组(P < 0.05),但至第5 天却表达显降&#65377;ST 作用3 d内胶原Ⅹ分泌量与对照组比较无差异,4 d起显著递增(P < 0.001)&#65377;②量效组:ST各个浓度点的软骨细胞胶原Ⅱ表达较基值均明显增加(P < 0.01),并以10-9 mol/L 最显&#65377;10-11 mol/L ~ 10-8 mol/L 的ST不增加胶原Ⅹ表达,至10-7 mol/L 始随剂量增加而增,10-5 mol/L 时达最高值(P < 0.01)&#65377;量&#65380;时效影响Ⅹ型胶原表达增加均迟于Ⅱ型,作用呈错峰性改变&#65377;【结论】 ST以时效和量效作用方式分别对雌激素受抑的离体青春期大鼠生长板软骨细胞的增殖呈双相影响,在合适的剂量和时间时,细胞增殖效应可达最好效果&#65377;     

雌孕激素替代治疗对特纳综合征患者骨密度的影响

对8例特纳综合征患者进行6年的雌孕激素补充治疗,比较治疗前后骨密度的变化。治疗前患者的骨密度明显低于同龄同性别的正常水平。经过6年性激素治疗后,患者的骨密度略有增加,但仍显著低于同龄同性别的正常水平。第2～4腰椎的骨密度从（0．75±0．12）g／cm^2增加到（0．84±0．22）g／cm^2,同龄同性别的z评分从-3．2±0．9升高到-2．2±0．6。髋部总体的骨密度从（0．68±0．07）g/cm^2增加到（0．81±0．08）g／cm^2,Z评分从-2．2±0．5增加到-1．2±0．3。长期雌孕激素补充治疗,可改善特纳综合征患者的骨密度,但不能使骨密度恢复到正常水平。