摘要
目的:观察聚乙二醇化重组人生长激素(PEGGH)在去脑垂体大鼠体内的(invivo)促进生长的生物活性功能和长效药理作用。方法:以摘除脑垂体的大白鼠为动物模型,PEGGHd1一次给药;rhGH(国家标准品)作为阳性对照,每天给药一次,连续6d,使总剂量与PEGGH一致。同时设模型组(去脑垂体大鼠),只给予0.1%牛血清白蛋白的生理盐水,d7处死大鼠,检测指标为:体重增加、尾长增长、胫骨骨骺板宽度和肝脏重量。结果:实验结果显示,与模型组比,PEGGH一次给药各剂量组体重显著增加(P<0.01),尾长也显著增长(P<0.01),胫骨骨骺板宽度显著增宽(P<0.01),中、高剂量组肝脏重量增加(P<0.01),并都具有量效关系;其促进动物生长的生物活性与每天给药的rhGH比没有差别(P>0.05),具有长效的作用,其中4.3、8.6IU·kg-1所至生物活性大于多次给药的普通rhGH8.6IU·kg-1效果;本批供试品测得生物效价为5.0IU·mg-1,比普通rhGH高1倍。结论:本批供试品PEGGH用药次数少、药效持续时间长,比普通rhGH具有更高的促进动物机体生长的生物活性。
AIM: To observe the long-term pharmacological effects and in vivo bioactivities in hypophysectomized (Hpx) male rats treated with Polyethylene glycolconjugated recombinant human growth hormone (PEG- GH). METHODS: A single subcutaneous ( s. c. ) injection of PEG-GH were administered to Hpx rats in 1 st day. Recombinant human growth hormone (rhGH) ( National standard) as control drug was treated by daily s.c. injections in Hpx rats for 6 days, which its total doses were same as PEG-GH. Model group (Hpx rats, n = 10) received 0.1% bovine serum albumin of normal saline only. Body-weight gain, tail-length gain, tibial epiphyseal growth plate width and liver-weight gain were tested in the end. RESULTS: The body-weight gain, tail-length gain tibial epiphyseal growth plate width and liver-weightgain were induced by single s.c. injection PEG-GH increased significantly than model group (P 〈 0.01 ), and no different from daily s.c. injections equimolar doses of rhGH solution for 6 days ( P 〉 0.05. There were doseresponses relation. The bioactivities for 4.2 IU·kg^-1 of PEG-GH were greater than that for 8.4 IU·kg^-1 of rhGH by daily for 6 days. The biopotency of PEG-GH was 5.0 IU·mg^-1 in bioassay using Hpx rats, which was increased by about 1-fold compared with unmodified rhGH. CONCLUSION: Single s.c. injection of PEG-GH shows the effects on body and organ growth and long-acting greater than those by daily s.c. injections of rhGH in Hpx rats.
出处
《中国临床药理学与治疗学》
CAS
CSCD
2005年第11期1270-1274,共5页
Chinese Journal of Clinical Pharmacology and Therapeutics