IGF-2、IGF-1R、IGF-2R在子宫内膜腺癌的表达及临床意义

目的:检测Ⅰ型子宫内膜癌中IGF-2及其相应受体(IGF-1R和IGF-2R/M6P)蛋白的表达情况,探讨IGF-2及其相应受体在Ⅰ型子宫内膜癌变中的表达及作用。方法:采用免疫组化PV法检测正常增生期子宫内膜(对照组)20例、子宫内膜腺癌(腺癌组)30例组织中IGF-2、IGF-1R和IGF-2R的表达情况。结果:IGF-2、IGF-1R的过阳性表达在Ⅰ型子宫内膜癌显著高于正常子宫内膜(P=0.007,P=0.006)。IGF-2R的阳性表达与过阳性表达在子宫内膜癌细胞均低于正常子宫内膜细胞(P=0.043,P=0.000)。结论:IGF-2R阳性表达的下调与IGF-2及IGF-1R的异常高表达在Ⅰ型子宫内膜癌的发生发展过程中起重要作用。     

胰岛素样生长因子-1及其结合蛋白与妊高征

妊娠高血压综合征是常见的严重危害母婴健康的妊娠并发症 ,目前其发病机理尚不明确。近年 ,许多学者提出胎盘或滋养细胞缺血与妊高征发病关系密切。胰岛素样生长因子 1及胰岛素样生长因子结合蛋白 1是生长发育的调节因子 ,被认为与滋养细胞的增殖或侵蚀有关。该文就胰岛素样生长因子 1及胰岛素样生长因子结合蛋白 1的生物学特性、与正常妊娠的关系及其在妊娠高血压综合征发生、发展中的作用进行综述。     

复方孕二烯酮对多囊卵巢综合征患者IGF-1、IGFBP-1、肾素-血管紧张素系统及促排卵结局的影响

目的:研究复方孕二烯酮(复方GES)对多囊卵巢综合征(PCOS)患者卵巢肾素-血管紧张素系统(RAS)、血清胰岛素样生长因子-1(IGF-1)、胰岛素样生长因子结合蛋白-1(IGFBP-1)、性激素水平及促排卵结局的影响并探讨其可能的作用机制。方法:选择PCOS患者40例,随机分为两组,实验组口服复方GES治疗,连续3个月。治疗前后分别测定血浆肾素原(PRA)、血管紧张素Ⅱ(ATⅡ)及血清IGF-1、IGFBP-1、空腹胰岛素(INS)、空腹血糖(GLU)、黄体生成素(LH)、促卵泡素(FSH)、雄烯二酮(A2)、雌二醇(E2)、睾酮(T),测量每侧卵巢内卵泡数目、卵巢体积并观察临床症状的改善及服药期间的副反应。停药后开始促排卵治疗。对照组直接进行促排卵治疗。结果:实验组服药3个周期后,FSH(P<0.05)、LH、A2、E2、T水平及LH/FSH比值(P<0.01)均显著下降,血浆PRA与ATⅡ水平显著降低(P<0.01),血清IG-FBP-1水平明显升高(P<0.05)。双侧卵巢体积显著缩小,卵泡数目明显减少(P<0.01)。临床症状得到缓解。促排卵治疗过程中,实验组HMG(或FSH)用量显著低于对照组(P<0.05),单卵泡生长率和HCG日A型内膜出现率高于对照组(P<0.05、P<0.01)。结论:复方GES能显著降低PCOS患者的血浆PRA及ATⅡ水平,提高血清IGFBP-1水平,降低LH、T、A2水平及LH/FSH比值,减少卵巢体积及卵泡数目,而对空腹INS及空腹GLU水平无明显影响;应用复方GES3个周期能明显改善PCOS患者CC+HMG方案促排卵治疗的效果。     

生长激素缺乏症患儿IGF-1与体质量指数的相关研究

目的 分析生长激素缺乏症(GHD)患儿的胰岛素样生长因子-1(IGF-1)与体质量指数(BMI)水平的关系。方法 回顾性分析137例GHD患儿的临床资料,每例均收集其身高(Ht)、体重(Wt)、BMI、血清生长激素(GH)、血清IGF-1等指标。结果 1)GHD患儿中IGF-1水平与BMI呈正相关;2)GHD患儿IGF-1水平受性别、BMI、青春期状态等因素的影响;3)GHD患儿中,在BMI SDS＜0.30组,BMI SDS每增加1个单位,IGF-1 SDS降低2%,差异无统计学意义(P>0.05);在BMI SDS≥0.30组,BMI SDS每增加1个单位,IGF-1 SDS增加93%,差异具有统计学意义(P<0.001);4)调整了性别、血小板、天门冬氨酸氨基转移酶、肌酐、高密度脂蛋白、促黄体生成素、促卵泡刺激素、雌二醇、睾酮、骨龄落后程度等混杂因素后,青春期前GHD患儿的BMI SDS每增加1个单位,IGF-1 SDS增加39.3%;青春期GHD患儿的BMI SDS每增加1个单位,IGF-1 SDS降低98.8%,差异均具有统计学意义(P<0.001或<0.05)。结论 GHD患儿的IGF-1水平受性别、BMI、青春期状态等因素的影响,并且适宜的BMI有利于促进GHD患儿的生长发育。GHD患儿在青春期前应适当增加BMI,进入青春期后应注意控制其BMI,这可能有助于IGF-1维持在较高水平,从而有利于其生长发育。     

复方孕二烯酮与二甲双胍联合应用对PCOS患者IGF-1、IGFBP-1、 肾素-血管紧张素系统及促排卵结局的影响

目的:研究二甲双胍与复方孕二烯酮(复方GES)对多囊卵巢综合征(PCOS)患者卵巢肾素-血管紧张素系统(RAS)、血清胰岛素样生长因子-1(IGF-1)、胰岛素样生长因子结合蛋白-1(IGFBP-1)、性激素水平及促排卵结局的影响并探讨其可能的作用机制。方法:选择PCOS患者40例,随机分为两组,实验组接受二甲双胍及复方GES治疗,连续3个月。治疗前后分别测定血浆肾素原(PRA)、血管紧张素Ⅱ(ATⅡ)及血清IGF-1、IGFBP-1、空腹胰岛素(INS)、空腹血糖(GLU)、黄体生成素(LH)、促卵泡素(FSH)、雄烯二酮(A2)、雌二醇(E2)、睾酮(T),测量每侧卵巢内卵泡数目、卵巢体积并观察临床症状的改善及服药期间的副反应。停药后开始促排卵治疗。对照组直接进行促排卵治疗。结果:实验组服药3个周期后,FSH(P<0.05)、LH、A2、E2、T水平及LH/FSH比值(P<0.01)均显著下降,血浆PRA、ATⅡ与空腹INS、BMI、INS/GLU比值显著降低(P<0.01)。IGFBP-1水平明显上升(P<0.05)。超声监测双侧卵巢体积显著缩小,卵泡数目明显减少(P<0.01)。促排卵治疗过程中,实验组HMG(或FSH)用量显著低于对照组(P<0.01),单卵泡生长率和HCG日A型内膜出现率均高于对照组(P<0.01),周期排卵率显著高于对照组(P<0.05)。结论:二甲双胍与复方GES合并用于PCOS患者,能改善PCOS患者内分泌水平,调节PCOS患者IR状态,显著提高PCOS患者CC+HMG方案促排卵治疗的效果,并减少促排卵并发症的发生。     

1-溴丙烷经口染毒致大鼠周围神经病模型的建立

目的 观察1-溴丙烷(1-bromopropane,1-BP)的周围神经毒性,建立1-BP经口染毒致周围神经病的动物模型.方法 40只雄性Wistar大鼠,随机分为低、中、高剂量组和对照组,每组10只;将1-BP溶于玉米油中,分别经口给予200、400、800 mg/kg的1-BP,对照组给予等体积玉米油,灌胃体积均为0.2 ml/100 g,每日1次,每周5d,连续16周.定期观察各组大鼠步态,测定后肢抓力和后肢撑力,染毒8周和16周时检测血液学和生化指标.结果 高剂量组染毒8～16周、中剂量组染毒14～16周和低剂量组染毒15、16周大鼠的步态评分均明显高于对照组,差异有统计学意义(P＜0.05,P＜0.01).与对照组比较,高剂量组染毒9、12、14周大鼠后肢抓力明显下降,差异有统计学意义(P＜0.05,P＜0.01);染毒16周时,动物后肢瘫痪.染毒16周时,中、低剂量组大鼠后肢抓力分别为对照组的72.6％和91.2％,差异有统计学意义(P＜0.01,P＜0.05).染毒12、14、16周时,高剂量组大鼠后肢撑力指数明显高于对照组;染毒14、16周时,中剂量组大鼠后肢撑力指数明显高于对照组,差异均有统计学意义(P＜0.05,P＜0.01).染毒8周高、中剂量组和染毒16周高、中、低剂量组血清中丙氨酸转氨酶(ALT)活力均明显低于对照组,差异均有统计学意义(P＜0.01).结论 神经系统是1-BP毒作用的敏感靶器官,1-BP暴露可导致大鼠周围神经病.     

Supplementation of Morin Restores the Altered Bone Histomorphometry in Hyperglycemic Rodents via Regulation of Insulin/IGF-1 Signaling

Pathological mechanisms underlining diabetic bone defects include oxidative damage and insulin/IGF-1 imbalance. Morin is a bioflavonoid with antioxidant and anti-diabetic effects. This study evaluates morin’s protective effects against altered bone histomorphometry in diabetic rats through assessing insulin/IGF-1 pathway as a potential mechanism. Diabetic animals were administered two morin doses (15 and 30 mg/kg) for 5 weeks. Different serum hepatic and renal functions tests were assessed. Bone density and histomorphometry in cortical and trabecular tissues were evaluated histologically. The expressions of insulin, c-peptide and IGF-1 were estimated. In addition, the enzymatic activities of the major antioxidant enzymes were determined. Diabetic-associated alterations in serum glucose, aminotransferases, urea and creatinine were attenuated by morin. Diabetic bone cortical and trabecular histomorphometry were impaired with increased fibrosis, osteoclastic functions, osteoid formation and reduced mineralization, which was reversed by morin; particularly the 30 mg/kg dose. Insulin/IGF-1 levels were diminished in diabetic animals, while morin treatment enhanced their levels significantly. Diabetes also triggered systemic oxidative stress noticeably. The higher dose (30 mg/kg) of morin corrected the endogenous antioxidant enzymatic activities in diabetic rats. Findings indicate the potential value of morin supplementation against hyperglycemia-induced skeletal impairments. Activation of insulin/IGF-1 signaling could be the underlining mechanism behind these effects.     

IGF-1增加脓毒症大鼠骨骼肌葡萄糖载体及其表达

目的:探讨胰岛素样生长因子-1(IGF-1)对脓毒症大鼠血浆应激激素及骨骼肌葡萄糖载体-4(GLUT-4)和mRNA表达的影响.方法:将SD大鼠采用盲肠结扎穿孔法(CLP)建立腹腔感染及颈静脉置管肠外营养(PN)模型后,随机分为脓毒症组(n=10)、PN组(n=10)和IGF-1组(n=10),另设正常组(n=10)仅行颈静脉置管输液.正常组和脓毒症组给予等渗盐水,自由进食和饮水,PN组给予营养支持,IGF-1组为PN IGF-1静脉注射,连续5d.第6 d测定血糖、胰岛素、高血糖素和IGF-1水平;免疫组化法测定骨骼肌GLUT-4及Real-Time PCR法测定GLUT-4 mRNA表达.结果:脓毒症大鼠血浆葡萄糖、胰岛素、高血糖素明显升高,IGF-1明显下降(P＜0.01).IGF-1组前三者较脓毒症组和PN组明显降低,IGF-1则明显升高(P＜0.05).脓毒症组骨骼肌GLUT-4及mRNA表达明显降低(P＜0.01);IGF-1组GLUT-4及mRNA表达较脓毒症组和PN组明显增加(P＜0.01).结论:IGF-1可改善应激激素之间的平衡,明显增加脓毒血症大鼠骨骼肌GLUT-4蛋白和mRNA的表达.     

赤霉素对雌性大鼠早期生长发育及胰岛素样生长因子表达水平的影响

目的探讨植物生长调节剂赤霉素对雌性SD大鼠生长发育及胰岛素样生长因子(IGF-1)表达水平的影响。方法选择刚断乳雌性SD大鼠40只,随机分为4组,即对照组,低、中、高赤霉素剂量组,分别按照0、2、100和200mg/kg赤霉素剂量经口灌胃,连续15天,每天记录身长、体重、阴道开口情况。染毒结束,剖杀受试动物,获得肝脏、卵巢、子宫,计算脏器系数。提取肝组织RNA进行RT-PCR,检测肝内IGF-1、胰岛素样生长因子捆绑蛋白(IGFBP-1)基因的表达水平。结果各组间大鼠的身长、体重,阴道开口时间,子宫、卵巢的脏器系数差异无显著性(P>0.05),肝组织内IGF-1、IGFBP-1平均表达水平差异亦无显著性(P>0.05),但高剂量组部分样本出现IGF-1、IGFBP-1表达强度倒置的现象。高剂量组动物的肝脏系数小于对照组(P<0.05)。结论在0～200mg/kg剂量范围赤霉素接触对雌性SD大鼠生长发育、肝脏内IGF-1及其捆绑蛋白的表达影响不明显,但200mg/kg剂量的赤霉素摄入可能对其肝脏产生损伤。     

生长激素缺乏症儿童重组人生长激素替代治疗前后IGF-1的动态变化

目的为了解重组生长激素（rhGH）治疗矮小症儿童前后类胰岛素生长因子-1（IGF-1）水平的变化，并对其有关因素进行研究分析。方法对57例应用rhGH治疗的矮小症患儿进行随访，包括23例完全性生长激素缺乏症（CGHD）和34例部分性生长激素缺乏症（PCHD）。以年龄、性别匹配20例儿童作为对照。在诊断时和治疗中每间隔3个月检查IGF-1、空腹血糖和胰岛素水平。结果与对照组比较，CGHD组和PGHD组GF-1水平偏低，其中对照组与CGHD组间差异具有显著性意义，IGF-1在治疗3个月时即明显上升，此后呈逐渐上升趋势。相关分析发现IGF-1与患儿年龄、胰岛素抵抗指数（HOMA-IR）、体重指数和治疗持续时间呈显著正相关，而与性别和激发GH峰值无显著相关。结论本研究证实矮小症儿童IGF—1偏低，经过rhGH治疗可使IGF-1升高，治疗中IGF-1水平与治疗时间、胰捣素抵抗有关。     

不同胎龄及体重新生儿血Ghrelin、胰岛素样生长因子-1、胰岛素样生长因子结合蛋白-3、胰岛素水平检测分析

目的:探讨Ghrelin与新生儿胰岛素-胰岛素样生长因子轴的关系,进一步揭示其对新生儿生长发育及能量代谢的影响。方法:选择62例新生儿,按胎龄、体重分为足月儿、早产儿、适于胎龄儿(appropriate for gestational age,AGA)和小于胎龄儿(small for gestational age,SGA)。其中胎龄30～34周14例,34+1～37周14例,37+1～41周34例。足月SGA13例,足月AGA 21例。检测血Ghrelin、胰岛素样生长因子-1(insulin-like growth factor-1,IGF-1)、胰岛素样生长因子结合蛋白-3(insulin-like growth factor binding protein-3,IGFBP-3)以及胰岛素、血糖水平,并在各组间进行比较。结果:30～34周、34+1～37周、37+1～41周3组比较Ghrelin浓度分别为(2.238±0.618)ng/ml(、1.226±0.37)ng/ml(、1.036±0.328)ng/ml,早产儿Ghrelin水平明显高于足月儿(P<0.01),且随着胎龄的增大差距减小;IGF-1分别为(43.214±16.723)ng/ml、(115.579±30.136)ng/ml、(153.292±26.633)ng/ml,IGFBP-3分别为(70.814±22.603)ng/ml、(123.300±28.666)ng/ml、(157.214±38.990)ng/ml,胰岛素分别为(1.032±0.812)μU/ml、(5.534±2.273)μU/ml、(14.654±3.064)μU/ml。IGF-1、IGFBP-3、胰岛素水平早产儿明显低于足月儿(P<0.01),足月SGA的Ghrelin水平明显高于AGA(P<0.01),IGF-1、IGFBP-3、胰岛素水平明显低于AGA(P均<0.01)。各组血糖水平无明显差异(P>0.05)。在SGA和AGA组Ghrelin分别与IGF-1、IGFBP-3及胰岛素呈明显负相关(P<0.01)。结论:SGA新生儿存在胰岛素-IGF轴的损害,IGF-1与胰岛素水平低下,从而使Ghrelin浓度反馈性的升高,以代偿其能量代谢的负平衡。     

Pubertal Growth,IGF-1, and Windows of Susceptibility: Puberty and Future Breast Cancer Risk

PurposeRisk markers for breast cancer include earlier onset of menarche (age at menarche [AAM]) and peak height velocity (PHV). Insulin-like growth factor-1 (IGF-1) is associated with pubertal milestones, as well as cancer risk. This study examined the relationships between pubertal milestones associated with breast cancer risk and hormone changes in puberty.MethodsThis is a longitudinal study of pubertal maturation in 183 girls, recruited at ages 6–7, followed up between 2004 and 2018. Measures included age at onset of puberty, and adult height attained; PHV; AAM; adult height, and serum IGF-1, and estrone-to-androstenedione (E:A) ratio.ResultsPHV was greatest in early, and least in late maturing girls; length of the pubertal growth spurt was longest in early, and shortest in late maturing girls. Earlier AAM was related to greater PHV. IGF-1 concentrations tracked significantly during puberty; higher IGF-1 was related to earlier age of PHV, earlier AAM, greater PHV, and taller adult height. Greater E:A ratio was associated with earlier AAM.ConclusionsFactors driving the association of earlier menarche and pubertal growth with breast cancer risk may be explained through a unifying concept relating higher IGF-1 concentrations, greater lifelong estrogen exposure, and longer pubertal growth period, with an expanded pubertal window of susceptibility.     

IGF-1, the Cross Road of the Nutritional,Inflammatory and Hormonal Pathways to Frailty

The decline in functional capacity is a heterogeneous phenomenon in the elderly. An accelerated ageing determines a frail status. It results in an increased vulnerability to stressors for decreased physiological reserves. The early identification of a frail status is essential for preventing loss of functional capacity, and its clinical consequences. Frailty and mobility limitation result from an interplay of different pathways including multiple anabolic deficiency, inflammation, oxidative stress, and a poor nutritional status. However, the age-related decline in insulin-like growth factor 1 (IGF-1) bioactivity deserves special attention as it could represent the ideal crossroad of endocrine, inflammatory, and nutritional pathways to frailty. Several minerals, namely magnesium, selenium, and zinc, appear to be important determinants of IGF-1 bioactivity. This review aims to provide an overview of the potential usefulness of nutrients modulating IGF-1 as potential therapeutic targets in the prevention of mobility limitation occurring in frail older subjects.     

血浆C肽水平变化早期预测2型糖尿病并发周围感觉神经病变的价值

目的 探讨血浆C肽水平变化早期预测2型糖尿病并发周围感觉神经病变的价值.方法 500例2型糖尿病予以震动觉、痛觉、温度觉、触压觉、踝反射检测,根据周围感觉神经检测结果分为四组：正常组（159例）、轻度异常组（120例）、中度异常组（121例）、重度异常组（100例）.同时测定其空腹和餐后2h血浆C肽,并与周围感觉神经变化进行分析.制作受试者工作特征（ROC）曲线,找出诊断糖尿病周围感觉神经病变的最佳临界点.结果 四组空腹血浆C肽比较差异无统计学意义（F=1.632,P＞ 0.05）.餐后2h血浆C肽从正常组到轻度异常组再到中度异常组逐渐增高[（1.110±0.526）、（1.324±0.490）、（1.573±0.716） μg/L],而到重度异常组[（0.910±0.465）μg/L]明显下降且低于正常组,差异均有统计学意义（P＜0.05）.当餐后2h血浆C肽为1.173 μg/L时,得到最大约登指数0.366.结论 糖尿病并发周围感觉神经病变的早期可能与空腹C肽水平变化关系不大,而与餐后2h血浆C肽水平变化有关.动态观察餐后2h血浆C肽水平变化可能有助于早期发现糖尿病周围感觉神经病变.     

胰岛素样生长因子在诊断儿童生长激素缺乏症中的临床价值

目的 探讨胰岛素样生长因子-1(IGF-1)、胰岛素样生长因子结合蛋白-3(IGFBP-3)检测在诊断矮小儿童生长激素缺乏症的临床价值。方法 收集65例临床诊断为矮小儿童血清标本,其中生长激素缺乏(GHD)组52例,特发性矮小症(ISS)组13例。收集46名健康儿童血清标本作为对照组。用化学发光法分别检测血清IGF-1和IGFBP-3浓度。结果 与对照组比较,GHD组和ISS组患儿血清IGF-1和IGFBP-3浓度均显著降低,差异均有统计学意义(P<0.05);GHD组血清IGF-1、IGFBP-3浓度分别为(105.53±75.22)ng/mL、(2.52±1.06)μg/mL,ISS组分别为(197.41±87.43)ng/mL、(3.61±1.50)μg/mL,差异有统计学意义(P<0.05)。结论 IGF-1、IGFBP-3可以为临床诊断矮小儿童生长激素缺乏症提供重要参考价值。     

甲乙煎对肝纤维化大鼠肝组织MMP2及TGFβ1表达的作用

目的观察中药甲乙煎对实验性肝纤维化大鼠基质金属蛋白酶 2（MMP2）及转化生长因子 1（TGFβ1）表达的作用。方法雄性清洁级Wister大鼠60只,随机分为正常对照组和肝纤维化模型组,运用二甲基亚硝胺对模型组大鼠诱导肝纤维化。4周后,将模型组大鼠随机分为模型对照组、甲乙煎高剂量［22 g/（kg·d）］组和低剂量［5.5 g／（kg·d）］组。对甲乙煎高、低剂量组大鼠分别给予甲乙煎灌胃,共治疗4周,处死全部大鼠。采用免疫组化法检测大鼠肝组织MMP2和TGFβ1的表达。结果经中药甲乙煎高、低剂量治疗后,甲乙煎高、低剂量组的大鼠肝细胞浆内TGFβ1的阳性表达与模型对照组比较,显著降低(P＜0.05),其中甲乙煎高剂量组优于低剂量组(P＜0.05);而甲乙煎高、低剂量组MMP2的表达较模型对照组无明显差异(P>0.05)。结论中药甲乙煎能下调实验性肝纤维化大鼠肝组织TGFβ1的表达,这是其抗肝纤维化的作用机制之一。     

辛伐他汀对骨质疏松大鼠血清细胞因子IL-6、IGF-I水平的影响

目的:观察辛伐他汀对去卵巢大鼠血清细胞因子IL-6和IGF-I水平的影响。方法:选择健康雌性Wistar大鼠27只,3月龄,体重(200±30)g,随机分为A、B、C3组,每组9只。A组行开关术,其余两组行双侧卵巢切除术。术后1周A、B两组均灌服生理盐水1.5ml/只/d,C组给予辛伐他汀5mg/kg/d,共10周。双能X线骨密度仪测量股骨和胫骨骨密度(BMD);ELISA定量测定血清细胞因子IL-6、IGF-I水平。结果:B组血清IL-6水平明显高于A、C组(P<0.001)。C组血清IGF-I水平与B组比较差异无显著性(P>0.05);A组血清IGF-I水平明显高于B组(P<0.001)。股骨BMD和胫骨BMD与血清IL-6水平均呈显著负相关(P<0.001),而与血清IGF-I水平均呈显著正相关(P<0.05)。结论:他汀类药物能够下调IL-6的表达水平;但对IGF-I影响作用不大。     

大鼠胚胎神经干细胞和PEP-1-SOD1融合蛋白 联合培养及鉴定

摘要:目的　探讨神经干细胞（NSCs）和PEP-1-SOD1联合培养对NSCs生长分化的影响。方法　孕14 d的SD大鼠进行NSCs的分离培养及鉴定后,NSCs和细胞转导肽PEP-1介导铜,锌-超氧化物歧化酶（Cu,Zn-SOD,SOD1）形成的PEP-1-SOD1融合蛋白联合培养。实验共分为4组,空白组:正常培养的NSCs,不予处理。低浓度组:NSCs在0.5 μmol/L PEP-1-SOD1的无血清培养基中培养。中浓度组:NSCs在2.5 μmol/L PEP-1-SOD1的无血清培养基中培养。高浓度组:NSCs在4.5 μmol/L PEP-1-SOD1的无血清培养基中培养。MTT法和免疫组化检测联合培养后对细胞增殖影响及细胞分化标志蛋白表达。结果　与不同浓度PEP-1-SOD1联合培养48 h后NSCs细胞增殖较空白组均出现明显的增殖活跃,差异有统计学意义（P＜0.05）;中、高浓度组较空白组及低浓度组差异有统计学意义（P＜0.05）;但中、高浓度2组之间差异无统计学意义（P＞0.05）。结论　2.5 μmol/L的 PEP-1-SOD1为比较适宜的NSCs培养浓度,培养48 h最有利于NSCs增殖。     

吗啡对拉米夫定抗HIV-1药效影响的体外MT2细胞实验研究

目的 探讨吗啡是否影响拉米夫定(3TC)抗HIV-1的抗病毒效果.方法 MT2细胞随机分为吗啡+3TC、吗啡+纳洛酮+3TC、纳洛酮+3TC处理组及3TC对照组和病毒对照组;用纳洛酮处理相应组的MT2细胞0.5 h后,加入吗啡处理细胞24 h,然后每组细胞加入等量的HIV-1ⅢB病毒和3TC溶液;病毒感染细胞第3、4、5和6天,取培养上清,用ELISA法检测培养上清的HIV-1 p24抗原,根据p24抗原表达量,计算各个处理组的3TC抗HIV-1 p24抗原抑制率.结果 HIV-1感染细胞第3和第4天,吗啡+3TC处理组的3TC抗HIV-1 p24抗原抑制率最低,与3TC对照组相比差异有统计学意义(P<0.05);吗啡+纳洛酮+3TC处理组和纳洛酮+3TC处理组的3TC抗HIV-1 p24抗原抑制率相当,两组差异无统计学意义(P>0.05),这两组分别与3TC对照组相比,差异无统计学意义(P>0.05);病毒感染细胞第5和第6天,各处理组的3TC抗HIV-1 p24抗原抑制率与3TC对照组相比,差异无统计学意义(P>0.05);各个处理组的3TC抗HIV-1 p24抗原抑制率随感染时间延长而降低,呈现时间一效应关系.结论 吗啡在病毒感染初期能降低3TC 的抗HIV-1药效;纳洛酮能够阻滞吗啡降低3TC的抗HIV-1药效作用.

Abstract：

Objective To determine whether morphine having the ability to influence the antiviral effect of lamivudine(3TC)in vitro study.Methods MT2 cells were randomly assigned into morphine+3TC treatment group,morphine+naloxone+3TC treatment group,naloxone+3TC treatment group.Both 3TC and virus control groups were set up.The corresponding MT2 cells were treated with opiates antagonist(naloxone)for 0.5 hours before the 24-hours morphine treatment program was implemented while all of the groups were then infected with equal amounts of cell-free HIV-1 ⅢB strain and 3TC.HIV-1 p24 antigen in culture supernatants collected at days 3,4,5 and 6after infection status was tested and the inhibition of 3TC anti-HIV-1 p24 antigen of various treatment groups calculated.Results Inhibition of 3TC anti-HIV-1 p24 antigen of Morphine+3TC treatment group was the lowest when HIV-1 infected cells at 3rd and 4th day and showed significant difierence (P<0.05)when compared to the 3TC control.However,there was no statistically significant difference among them(P>0.05),when virus was infected the cells at 5th and 6th day.The difference of 3TC anti-HIV-1 p24 antigen inhibition between the morphine+naloxone+3TC treatment group and the naloxone+3TC treatment group was not significant(P>0.05).Similar results were obtained when these two groups were compared to the 3TC control group(P>0.05),respectively.The 3TC anti-HIV-1 p24 antigen inhibition of each treatment group reduced as the time of infection prolonged,showing a significant and time-course effbct.Conclusion The 3TC antiviral effect was reduced by morphine in the early stage of infection,and could be blocked by naloxone.