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作 者:章建伟[1] 张涛[1] 吴满武[1] Zhang Jianwei
出 处:《浙江临床医学》2021年第2期159-161,共3页Zhejiang Clinical Medical Journal
基 金:浙江省医药卫生科技计划(2017KY668);金赛中青年科研基金(PEGRF201607001)。
摘 要:目的研究重组人生长激素(thGH)治疗GnRHa干预后性早熟大鼠生长减速的效果,并探究可能的治疗机制。方法选取48只正常SPF級雌性SD大鼠随机分为8组,每组各6只。A组:正常大鼠对照组,B组:性早熟大鼠模型组,C组:GnRHa 1000μg/kg,D组:GnRHa 800μg/kg,E组:GnRHa 600μg/kg,F组:tGH+GnRHa 1000μg/kg,G组:thGH+GnRHa 800μg/kg,H组;rhGH+GnRHa 600μg/kg。达那唑造模成功后,给药组大鼠分别給予GnRHa制剂曲普瑞林,2周强化治疗1次,4周末时对F、G、H组大鼠加用thGH制剂[1 IU/(kg·d)],8周末时结束。检测大鼠体征、采用ELISA法测定性早热模型大鼠血清IGF-1指标、HE染色观察性早熟大鼠胫骨、Western Blot检测生长板软骨中PGP2、FGFR3、ICF-1R蛋白的表达情况。结果与性早熟大鼠模型组相比,给药组大鼠的体重、鼻尾长度和胫骨长度出现极显著增长(P<0.01);软骨生长板细胞破坏程度较轻,细胞形态较为正常;软骨组织中的FGF2、FGFR3、IGF-1R蛋白表达水平极显著上升(P<0.01),且与给药剂量呈正相关。结论GnRHa联合thGH使用在大鼠性早熟模型中治疗生长减速效果明显优于GnRHa单独给药,可能与IGF、IGF-1R.FGF2、FGFR3蛋白的相互作用和信号介导有关。Objective To study the eft of rhGH treatment on growth velocity in precocious puberty rats after GnRHa intervention,and to.explore possible therapeutic mechanisms.Methods Forty-eight normal SPF female SD rats were randomly divided into 8 groups,6 rats in each group.Group A:normal control group,group B:precocious puberty rat model group,group C:GnRHa 1000μg/kg,group D:GnRHa 800μg/kg,group E:GnRHa 600μg/kg,group F:thGH+GnRHa 1000μg/kg,G group:rhGH+GnRHa 800μg/kg,H group:thGH+GnRHa 600μg/kg.After model was susfuly establisbhed by the danazol,nts in the treatment group were given GnRHa(triptorein),intensive treatment once every 2 weeks,and thGH preparations were added to rats in groupsF,G,and Hat the end of4 weeks[1 IU/(kg·d)],the end of the 8th weekend.The signs of rats were detected,the serum IGF-1 indexes of precocious puberty model rats were decermined by ELISA,the tibia of precocious puberty ras were observed by HE staining,and the expression ofFGF2,FGFR3 and IGF-IR protein in the growth plate carilage was detected by Western Blot.Results Compared with the precocious puberty rat model group,the body weight,nasal tail length and tibia length of the rab in the treatment group increased signifcandly(P<0.01),the damage of cartilage growth plate cells was lighter,and the cell morphology was relatively normal.The expresion levels ofFGF2,FGFR3 and IGF-1R proteins in tssues increased signifcantly(P<0.01),and were positively correlated with the dose.Conclusion The efect of GnRHa combined with rhGH in the treatment of precocious puberty in rats is significantly better than GnRHa alone,which may be relted to the interaction and signal mediation ofIGF,1GF-IR,FGF2,and FGFR3 proteins.
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