Pro-Pro-hGHRH(1-44)OH的体外活性分析及其对四氧嘧啶糖尿病大鼠影响的研究-东南大学学报医学版

Pro-Pro-hGHRH(1-44)OH的体外活性分析及其对四氧嘧啶糖尿病大鼠影响的研究

单位：1.东南大学,临床医学院,江苏,南京,210009； 2.东南大学附属中大医院,核医学科,江苏,南京,210009

关键词：Pro-Pro-hGHRH(1-44)OH 生长激素释放激素类似物生长激素释放激素生长激素类胰岛素样生长因子-1 四氧嘧啶糖尿病大鼠

分类号：R587.1, R-33

出版年·卷·期（页码）：2006·25·第五期（369-372）

摘要：

目的:进一步验证Pro-Pro-hGHRH(1-44)OH的生物活性,并观察其对糖尿病(DM)大鼠GHRH-GH-IGF-1轴的影响.方法:(1)取正常大鼠垂体6个,每个垂体分为3份后在体外孵育,将垂体随机分成4组,分别加入0.01、0.1、1.0 mg·L-1的Pro-Pro-hGHRH(1-44)OH和2.0 mg·L-1hGHRH,测定加药前、后GH含量改变.(2)将DM大鼠随机分为GHRH类似物组、GHRH组和DM对照组,分别给予Pro-Pro-hGHRH(1-44)OH 1 mg·L-1、hGHRH(1-44)OH 2 mg·L-1和0.9%生理盐水,另取正常大鼠作为正常对照,测定DM 3组和正常对照组血GH、IGF-1和胰岛素含量.结果:(1)Pro-Pro-hGHRH(1-44)OH体外活性结果示,0.1、1.0 mg·L-1的Pro-Pro-hGHRH(1-44)OH与hGHRH组3组之间比较,均P＜0.05.(2)DM 3组和正常对照组血胰岛素含量结果示,正常对照组与DM 3组之间比较,均P＜0.01.血IGF-1含量4组之间比较均P＞0.05.血GH含量DM对照组与正常对照组之间比较,P＜0.05.GHRH组与DM对照、正常对照组3组之间比较,均P＜0.05.结论:Pro-Pro-hGH-RH(1-44)OH是一种具有强大促GH分泌活性的GHRH类似物,这种活性存在剂量依赖性,当四氧嘧啶DM大鼠给予Pro-Pro-hGHRH(1-44)OH后,能显著增加DM大鼠垂体的敏感性.

Objective To testify the biological activity of ProPro-hGHRH(1-44)OH and observe its effect on the GHRH-GH-IGF-1 axis of alloxan diabetes rats.Methods(1)6 pituitaries of normal rats were resected and cut into 3 pieces for in vitro incubation.All these pieces were randomly divided into four groups,whose incubation buffer was added with Pro-Pro-hGHRH(1-44)OH 0.01,0.1,1.0 mg·L^{-1} and hGHRH 2.0 mg·L^{-1} respectively.The change of GH concentration was observed.(2)DM rats were divided into 3 groups randomly: group GHRH analog was treated with Pro-Pro-hGHRH(1-44) OH 1 mg·L^{-1} intraperitoneally,Group GHRH treated with hGHRH 2()mg·L^{-1} intraperitoneally,group DM control treated with 0.9% NS.Additionally,normal rats were taken as controls.The concentrations of GH、IGF-1 and insulin of the 4 groups were measured and compared.Results(1)In vitro activity assays of Pro-Pro-hGHRH(1-44)OH revealed differences among the group of Pro-Pro-hGHRH(1-44)OH 0.1 mg·L^{-1},1.0 mg·L^{-1}and hGHRH 2.0 mg·L^{-1},P<0.05.(2)Insulin concentrations showed differences between the DM groups and normal control,P<0.01.(3)The IGF-1 concentrations had no difference compared between any two groups,P>0.05.(4)The GH concentrations had differences between group DM control and any other group as well as between group GHRH analog and group GHRH,P<0.05.Conclusion Pro-Pro-hGHRH(1-44) OH is a new GHRH analog with potent GH-releasing ability in a dose-dependent manner.Pro-Pro-hGHRH(1-44) OH can greatly increase the pituitary sensitivity of(alloxan diabetes) rats,but IGF-1 does not increase as greatly as GH does.

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