重组人生长激素对肝移植术后早期营养状态及免疫功能影响的前瞻性研究

目的 评价重组人生长激素（rhGH）结合营养支持治疗在肝移植术后早期对患者营养状态及免疫功能的影响,观察其对肝功能、急性排斥反应及感染发生率是否具有影响,以及临床应用的安全性。方法 60例良性终末期肝病患者于肝移植前被随机分为治疗组（n=30）及对照组（n=30）。两组术后均予营养支持及免疫抑制剂治疗,其中治疗组于术后24h给予rhGH（思增）10U/d皮下注射10d。于术后1、4、8和14d采集静脉血,观察转铁蛋白、前白蛋白、白蛋白、尿素氮等营养指标;CD4/CD8、免疫球蛋白G（IgG）、IgM、IgA等免疫指标;生长激素（GH）、胰岛素样生长因子-1（IGF-1）、天冬氨酸转氨酶（AST）、丙氨酸转氨酸（ALT）水平;维持血糖安全范围（8~10mmol/L）所需胰岛素用量;术后28d内急性排斥反应发生率（肝穿活检）及感染发生率。结果与对照组比较,治疗组14d内转铁蛋白、前白蛋白、CD4/CD8、GH、IGF-1水平显著升高（P均〈0.05）,尿素氮水平明显下降（P〈0.05）;治疗组术后4d和8d控制血糖所需外源性胰岛素用量明显大于对照组（P均〈0.05）;术后14d白蛋白使用量明显低于对照组（P〈0.05）;两组14d内AST、ALT水平及28d内急性排斥反应和感染发生率比较差异均无显著性。结论 在使用免疫抑制剂的前提下,rhGH结合营养支持治疗可以加速改善肝移植术后患者的营养不良,未体现提高机体免疫力的优势,对术后移植肝功能恢复、急性排斥反应及感染发生率未见显著影响。由于其所致血糖升高降低了其安全性。     

严重烧伤后应用重组人生长激素对机体免疫功能的影响

目的:观察重组人生长激素(rhGH)对严重烧伤病人免疫功能的影响。方法:24例临床烧伤患者分为rhGH治疗组(GH组)和生理盐水对照组(对照组),分别于伤后3、10、17d检测血清GH,血清胰岛素样生长因子-1(IGF-1),血清胰岛素样生长因子结合蛋白-3(IGFBP-3),外周血IgG、IgA、IgM、CD4、CD8、CD4/CD8比值及自然杀伤细胞活性变化。结果:GH组伤后第10、17天血清GH、IGF-1、IGFBP-3值均明显高于对照组(P<0.05或P<0.01),各免疫指标烧伤后均出现不同程度的下降,GH组IgG、IgA在伤后17d明显高于对照组(P<0.05或P<0.01),GH组CD4值在伤后10、17d明显高于对照组(P<0.05或P<0.01),CD4/CD8值在伤后17d均明显高于对照组(P<0.01),CD8值两组各时相点差异无统计学意义,GH组自然杀伤细胞活性伤后17d明显高于对照组(P<0.05)。结论:严重烧伤后应用rhGH能促进烧伤机体免疫功能的恢复。     

大鼠肾移植急性排斥模型建立研究

目的建立大鼠肾移植急性排斥反应模型,探讨肾移植组织病理机制。方法 78只正常雄性SD大鼠分为正常对照组（A组）15只,模型组（B组）15只,非急性排斥组（C组）16只（以SD大鼠为供体）,急性排斥组（D组）16只（以Wistar大鼠为供体）,观察术后第7天各组SD大鼠肾功能变化,术后第7天切取移植肾,光镜下观察组织病理改变,参照Banff 97诊断标准,进行急性排斥反应严重程度的半定量评分。结果 C,D组尿素氮、肌酐水平及急性排斥反应半定量评分明显高于A组（P〈0.05）,D组明显高于C组（P〈0.01）。结论 Wistar-SD大鼠移植模型可作为大鼠肾移植急性排斥模型。     

大鼠肾移植急性排斥模型的建立

目的建立大鼠肾移植急性排斥反应（AR）模型,进行移植免疫机理的研究。方法正常雄性Wistar大鼠肾脏为正常对照组（control组）;Wistar大鼠作为供受者建立同系基因对照组（sTX组）;SD大鼠为供者,Wistar大鼠为受者建立同种异体基因移植组（aTX组）;SD大鼠为供者,Wistar大鼠为受者,术后给予环孢素A（CsA）免疫抑制建立同种异体基因移植免疫抑制组（aTX＋CsA组）。术后第3、5、7天分别切取移植。肾,进行HE、Masson、PAS、PASM染色,光镜下观察病理改变,参照Banff97诊断标准,进行AR严重程度的半定量评分。结果与control组相比较,术后第3、5、7天aTX组AR半定量评分明显升高（P〈0．01）;sTX组AR半定量评分升高,但无统计学差异（P〉0．05）;aTX＋CsA组AR半定量评分也升高,但无统计学差异（P〉0．05）。术后第3、5、7天aTX组与sTX组相比较AR半定量评分明显升高（P〈0．01）;与aTX＋CsA组相比较AR半定量评分明显升高（P〈0．01）。aTX组中两两比较,第5、7天AR半定量评分与第3天相比较明显升高（P〈0．05）,第5天和第7天评分相比较无统计学差异（P〉0．05）。sTX组和aTX＋CsA组中术后第3、5,7天两两比较均无统计学差异（P〉0．05）。结论Wistar-Wistar大鼠肾移植后,AR出现晚,排斥程度轻微,可以作为大鼠肾移植急性排斥模型的对照组;SD—Wistar大鼠肾移植后可出现明显的AR,因此,SD-Wistar大鼠移植模型可以作为大鼠。肾移植急性排斥模型;CsA治疗可以明显减轻或抑制大鼠肾移植AR的发生。     

肾移植术后急性排斥反应的早期观察和护理

目的:探讨肾移植术后急性排斥反应的早期观察、护理及其作用。方法:对我院82例肾移植术后早期急性排斥反应患者临床资料进行回顾性分析、总结。结果:急性排斥反应的症状和体征较典型的有56例,不明显者26例。74例急排逆转。伴有并发症者46人次,其中8例移植肾破裂,修复成功5例,3例摘除移植肾;1例并发高血压脑病患者死亡;其余各例均好转。结论:对肾移植术后早期患者密切观察和仔细护理有助于及时发现急排及其并发症。对不典型的急排患者更应加强观察和护理。     

肾移植术后急性排斥反应的临床观察及护理措施

目的 总结肾移植术后急性排斥反应的主要临床症状和表现,并提出相应的护理措施,以指导临床护理工作。方法 回顾性统计36例肾移植术后患者发生排斥反应时的临床症状和表现,并进行分析。结果 尿量减少及体温增高是急性排斥反应发生时的首要和集中表现,其次为血压升高和体重增加,另外也可表现为移植。肾胀痛等。结论 肾移植术后,护士应加强患者出入量及生命体征的观察,了解患者的主诉,采取预见性护理,以有效判断肾移植术后急性排斥反应的发生,为抗排斥治疗争取时间。     

重组人生长激素对化疗大鼠肾脏的影响

目的利用卡铂和氟尿嘧啶建立大鼠肾损伤模型，探讨重组人生长激素（rhGH）对化疗药肾毒性的影响，了解rhGH能否减轻化疗肾毒性。方法实验分空白对照组、生理盐水组、rhGH组、化疗组和化疗＋rhGH组。给药后第7d、14d、21d和28d应用血液全自动生化分析仪检测实验各组大鼠血清肌苷（Cr）、尿索氮（BUN）及白蛋白（Alb）作为实验参数，并行肾组织病理及免疫增殖核抗原（PCNA）检测。结果给药后第7d、14d化疗组和化疗＋rhGH组血清Cr、BUN较其它组明显升高（P〈0．05）。第21d,28d化疗＋rhGH组血清Cr和BUN较化疗组降低（P〈0．05）。第28d化疗＋rhGH组血清Cr和BUN与溶剂对照组比较无统计学意义（P〉0．05），化疗组则仍高于其它各组（P〈0．05）。第7d、14d、21d和28d溶剂对照组与rhGH组比较均无显著差异（P〉0．05）。第7d和14dAlb检测溶剂组和rhGH组均高于化疗组和化疗＋rhGH组（P〈0．05）；第21d、28d化疗＋rhGH组Alb已明显回升与溶剂对照组接近（P〉0．05），较化疗组明显升高（P〈0．05）。结论①rhGH单独短期应用不会导致肾功能改变；②rhGH与化疗药合用不会增加化疗药的肾毒性；③rbGH能减轻化疗药的肾毒性。     

OKT3治疗肾移植术后急性排斥反应的观察及护理

目的探讨OKT3治疗肾移植术后急性排斥反应的护理方法。方法对4例慢性肾功能衰竭行同种异体肾移植术后发生急性排斥反应的患者应用OKT3进行治疗,治疗前给予心理护理,减轻患者的焦虑,使其很好地配合治疗;治疗期间重点做好不良反应的护理,预防及减轻不良反应的发生。结果治疗过程中未出现感染、肺水肿等不良反应。结论精心的护理可预防和减轻OKT3的不良反应的发生,提高治疗效果。     

肾移植术后发生急性排斥反应患者舒适状况研究

目的了解肾移植术后发生急性排斥反应患者的舒适状况,为舒适护理提供依据。方法采用肾移植受者舒适量表于2005年11月-2006年8月对22例。肾移植术后发生急性排斥反应逆转后的患者进行调查。量表根据。肾移植受者特点,在美国舒适护理专家Kolcaba研制的简化舒适状况量表（GCQ）基础上修订而成。结果。肾移植术后发生急性排斥反应的患者整体舒适感不高[分（56．91±6．74）分,总分100分,62．5分以下为舒适感差]。在精神心理领域主要存在对疾病康复担心引起的沮丧、焦虑、不确定感以及缺乏信心等不适;生理不适主要是疲乏、疼痛、口渴、入睡困难及胃肠不适等;社会领域的不适主要体现为缺乏康复相关知识及他人的理解和同情以及对经济的担忧。经多元逐步回归分析表明影响其舒适的主要人口学因素是性别（X1）和住院费用来源（X7）,回归方程为：y^^=63．44—8．07X1＋2．66X7。结论。肾移植术后发生急性排斥反应的患者在精神心理和生理领域舒适感差,社会领域和环境领域舒适感相对较好。从缓解精神心理不适、促进生理舒适及社会支持、营造舒适的病房环境等方面针对性地提出健康教育、按麾、缓解疼痛、满足睡眠习惯、促进社会支持等舒适护理措施。     

基因重组人生长激素对严重烧伤后的康复作用

目的探讨基因重组人生长激素(rhGH)对蛋白质合成的影响及其在严重烧伤病人治疗中的作用.方法选择28例烧伤总面积>35%TBSA,III度面积>15%TBSA病人作为观察对象,随机分组,治疗组(rhGH组)15例和对照组13例.rhGH组病人术后每日由皮下按照0.2IU/kg.给予rhGH治疗共10d,对照组按相同方法给2ml生理盐水作安慰剂对照,伤后观察病人一般状况,测血常规、血生化、肝功(包括谷丙转氨酶ALT),植皮区、供皮区创面愈合时间及住院日期.结果rhGH治疗组供、植皮区创面愈合时间缩短,血浆总蛋白、白蛋白浓度提高,全身感染并发症例数减少,差异显著.结论rhGH可有效促进血浆蛋白质的合成,纠正机体负氮平衡,减少全身感染并发症、内脏并发症发生机会,促进创面愈合,缩短住院时间.     

Absorption of recombinant human growth hormone (rhGH) following intraperitoneal instillation

Recombinant human growth hormone (rhGH) was instilled intraperitoneally (i.p.) in six children undergoing continuous cycling peritoneal dialysis (CCPD). Immediate absorption was noted with either 0.250 mg/kg, 0.125 mg/kg, or 0.050 mg/kg of rhGH. Peak serum growth hormone (GH) levels occurred 4 and 8 h following i.p. administration, and the serum GH levels had returned to baseline values at 24 h. In one patient, a higher dosage demonstrated adequate absorption, whereas the lower dosage produced a flat absorption curve. These data indicate that daily i.p. administration of rhGH could be utilized in clinical trials directed toward improving the growth velocity of children undergoing CCPD.     

Recombinant human growth hormone (rhGH) treatment of children undergoing peritoneal dialysis

The authors studied the effect of recombinant growth hormone (rhGH) treatment on 5 growth retarded children, age 2 2/12 to 17 8/12 years, who had end-stage renal disease (ESRD) and were undergoing continuous cycling peritoneal dialysis (CCPD). Patients received 0.125 mg/kg of subcutaneous rhGH 3 times weekly. Accelerated height velocity compared to the previous year of CCPD was noted in 2 patients and improvement in the standard deviation score (SDS) as a parameter of improved growth velocity was noted in a third patient. This was associated with an increase in weight and improvement in the midarm muscle circumference (MAMC) suggesting an anabolic effect of rhGH treatment. Bone age advancement was consistent with the period of observation; no advancement greater than that expected for the increase in chronological age was observed. No significant side effects were attributable to rhGH therapy. These preliminary results indicate some growth retarded children without growth hormone deficiency with ESRD undergoing CCPD may respond to exogenous rhGH therapy with an acceleration in growth velocity: However, the failure to achieve uniform acceleration of height velocity indicates the need for controlled studies before rhGH can be recommended for all growth retarded children with ESRD undergoing peritoneal dialysis.     

重组人生长激素对大鼠肝移植后胆汁淤积的调节作用

背景:胆汁淤积是肝移植后的常见并发症之一,严重胆汁淤积可能伴随着不可逆性的肝功能损害.肝移植后早期应用重组人生长激素,能促进移植肝功能的恢复.目的:拟验证重组人生长激素对大鼠肝移植后胆汁淤积的调节作用.设计、时间及地点:细胞分子水平的随机对照动物实验,于2005-12/2006-12在东方肝胆外科医院及解放军第二军医大学动物实验中心完成.材料:选用Wistar大鼠105只,按随机数字表法分为3组,假手术组21只;其余大鼠配对建立大鼠肝移植模型后,分为生长激素组和肝移植组(n=21).方法:生长激素组大鼠肝移植后即予皮下注射重组人生长激素2U/(kg·d)至处死日;其他组同时皮下注射等量生理盐水.假手术组仅做开腹和关腹,游离肝脏并不行肝移植.主要观察指标:各组分别于移植后1,3,7 d处死取材(n=7),采集血清样本检测碱性磷酸酶、谷氨酰转肽酶、谷丙转氨酶活性及总胆汁酸、总胆红素含量等肝功能指标;应用放射免疫法检测生长激素:取肝组织样本,应用免疫组织化学和聚合酶链反应方法分析毛细胆管膜面上多耐药相关蛋白2和胆盐输出泵表达水平,并对以上指标进行相关性分析.结果:[1]肝移植组人鼠在移植后早期出现胆汁淤积,移植后1,3 d的各项肝功能指标均高于假手术组(p<0.05),术后7 d呈下降趋势.[2]生长激素组与肝移植组同期比较,胆汁淤积程度降低,恢复迅速.[3]肝移植组肝脏多耐药相关蛋白2在毛细胆管膜上定位减少、向胞浆内分布,表达亦明显下调;生长激素组大鼠的肝脏多耐约相关蛋白2表达水平明显增高,恢复加快.[4]胆盐输出泵的表达在各组问差异无显著性意义(P>0.05).[5]肝组织多药耐药相关蛋白2表达与血清生长激素呈正相关(r=0.8592,P<0.05);与血清胆红素呈负相关(r=0.777 2,P<0.05).结论:多耐约相关蛋白2的表达减少以及定位异常可能是肝移植后胆汁淤积发生的主要分子途径之一,重组人生长激素促进胆红素的转运可能是通过直接上调多耐药相关蛋白2表达来实现,胆盐输出泵不参与肝移植后早期胆汁淤积.     

Effects of human recombinant growth hormone (rhGH) on inflammatory responses in patients undergoing abdominal aortic aneurysm repair

Background: Human recombinant growth hormone (rhGH) has been shown to increase skeletal muscle protein synthesis and improve nitrogen balance in critically ill patients and those undergoing surgery. rhGH effects on hepatic protein turnover in critically ill patients are less clearly understood. Objective: To examine rhGH effects on hepatic acute phase protein responses and inflammatory cytokine release in patients undergoing major surgery. Design: Prospective double blind randomised trial. Setting: Tertiary referral university teaching hospital. Patients: Patients undergoing elective abdominal aortic aneurysm repair. Intervention: Patients received rhGH (Genotropin, 0.3 IU/kg per day, n = 8) or placebo (n = 10) for 6 days prior to surgery. Results: Blood levels of growth hormone (GH) and insulin-like growth factor (IGF-1) were measured following rhGH treatment and C-reactive protein (CRP), serum amyloid A (SAA) and the cytokines interleukin-6 (IL-6) and the IL-1 receptor antagonist (IL-1ra) were measured for up to 24 h following surgery. Significant increases in plasma rhGH (0.84 ± 0.3, mean (sem) versus 52 ± 20 mU/l, p < 0.0008) and IGF-1 levels (119 ± 13 versus 644 ± 110 ng/ml, p < 0.0001) were seen prior to surgery following rhGH administration. No differences in acute phase protein or cytokine levels were seen following surgery in patients receiving rhGH. Conclusions: These results indicate that pre-operative administration of rhGH does not alter acute phase protein or inflammatory cytokine release in response to major surgery. Received: 3 June 1997 Accepted: 6 November 1997     

Altered plasma cytokines and total glutathione levels in parenterally fed critically ill trauma patients with adjuvant recombinant human growth hormone (rhGH) therapy

OBJECTIVES: Glutathione (GSH) is a potent endogenous antioxidant that serves as one of the body's most important defenses against oxygen metabolites. Plasma levels of GSH are maintained primarily by a balance between secretion from the liver and degradation in the kidney. The ability to maintain and enhance tissue GSH may be of particular importance in controlling cytokine production in response to a stimulus like injury. The interaction after severe trauma between GSH and cytokines, tumor necrosis factor (TNF) -alpha, and interleukin (IL)-6, are not known. The purpose of the study was to investigate the levels of plasma GSH and cytokines TNF-alpha and IL-6 in adult patients admitted to the intensive care unit of our level I trauma center who were treated with recombinant human growth hormone (rhGH) for > or =7 days. DESIGN: Prospective, randomized, controlled trial. SETTING: Trauma intensive care unit. PATIENTS: Twenty-eight patients with multiple injuries and 14 normal postabsorptive controls. INTERVENTIONS: From 48-60 hrs after injury, when resuscitation was complete, a stable hemodynamic status was achieved and the patients were receiving maintenance fluid without nitrogen or calories, a blood sample was drawn for basal, plasma GSH, TNF-alpha, and IL-6 measurement. Intravenous feeding was then started and continued for 7 days. The patients were randomized to receive or not to receive daily intramuscular doses of recombinant human growth hormone (0.15 mg rhGH/kg/day). Daily morning plasma was obtained for analysis of GSH, TNF-alpha, and IL-6 levels. RESULTS: In the early catabolic "flow phase" of severe injury, the plasma levels of GSH were not altered but plasma TNF-alpha and IL-6 levels were increased significantly, compared with uninjured controls. Seven days of total parenteral nutrition alone enhanced plasma GSH levels (76%), but no change in TNF-alpha was observed. Supplementation with rhGH enhanced GSH (180%), and TNF (65%) with no changes in IL-6 levels. There is a significant linear relationship between plasma GSH and TNF-alpha levels in our rhGH-supplemented trauma patients. CONCLUSION: Modification of plasma GSH and TNF-alpha levels by adequate nutritional support with adjuvant rhGH during the postinjury period demonstrates the beneficial role of GSH in enhancing antioxidant defenses.     

rhGH对肠道缺血再灌注损伤大鼠促炎介质介导性肺损伤的影响

目的:观察重组人生长激素(rhGH)对肠道缺血再灌注(GIR)损伤大鼠促炎介质介导性肺损伤的影响.方法:42只Wister大鼠随机分为GIR损伤组和治疗组,每组分为缺血前30 min,再灌注后48 h和72 h3个时相点(n=6).治疗组分别于再灌注后3 h和12 h使用rhGH向大鼠腹壁皮下注射1 U/kg,每间隔12 h追加一次.采用夹闭肠系膜前动脉(60 min)技术复制GIR损伤大鼠模型.观察各时相点:(1)血浆内毒素(LPS)和肿瘤坏死因子(TNF-α)水平的变化;(2)肺组织中髓过氧化酶(MPO)、弹性蛋白酶(NE)、磷脂酶A2(PLA2)活性的变化;(3)肺组织湿干重比值(W/D)的变化.结果:成功复制了大鼠GIR损伤模型,rhGH用药后可引起:(1)血浆LPS和INF-α水平与GIR组比较明显降低(P<0.01或P<0.05);(2)再灌注3 h和12 h用药组肺组织PLA,含量与GIR组比较在再灌注后48 h显著下降(P<0.05,P<0.01),其余时象点MPO、PLA2、NE活性与GIR组比较有不同程度变化,但均无统计学意义;(3)再灌注后3 h用药组肺组织的W/D与GIR组比较有显著差异(P<0.05).结论:rhGH能减轻促炎介质介导性肺损伤,可能与降低GIR损伤大鼠血液中LPS和TNF-α的水平和肺组织中PLA2活性有关.     

脓毒症急性肾损伤与免疫功能的相关性研究

目的 探讨脓毒症急性肾损伤(SAK(I)与机体免疫状态之间相关性,为临床对脓毒症急性肾损伤可预见性的诊断、处理提供依据.方法 采用回顾性研究方法,以北京协和医院急诊监护室2013年1月至2014年9月期间收治的91例成人脓毒症患者为研究对象,根据是否合并有继发性免疫缺陷病(SID)分为免疫缺陷组46例和对照组45例;并根据2012年“改善全球肾脏病预后组织”(KDIGO)指南确立的急性肾损伤诊断标准及分期,将两组的SAKI患者分为非SAKI组(16/23例)、KDIGO-1期组(15/13例)、KDIGO-2期组(11/1例)、KDIGO-3期组(4/8例).对两组SAKI各期发病率、合并SAKI患者的肾功变化及病情进展速度进行比较.结果 免疫缺陷组与对照组在KDIGO-2期发病率差异具有统计学意义(23.9％vs.2.2％,x2=0.321,P=0.002),KDIGO-1期及3期发病率比较无统计学意义(1期:32.6％vs.29.8％,x2=0.040,P=0.701;3期:8.7％vs.17.8％,x2=-1.805,P=0.200).两组中SAKI患者在△Scr、△eGFR等肾功指标变化、用患者出现SAKI天数及发展至SAKI最严重期天数所表达的病情进展速度比较差异无统计学意义(P＞0.05).结论 继发性免疫缺陷病患者脓毒症急性肾损伤严重程度较正常患者无显著差异.免疫应答过程中炎症介质所导致的肾损伤可能不是脓毒症急性肾损伤的主要机制.