Effect of two human growth hormone receptor antagonists on glomerulosclerosis in streptozotocin-induced diabetic rats  

作　　者：WeiLI Li-huaZHU En-biWANG Zeng-canYE JunLIN Li-heGUO Fei-hongLUO Xi-hongLIU XinFANG Shui-xianSHEN 

机构地区：[1]InstituteofBiochemistryandCellBiology,ShanghaiInstitutesforBiologicalScience,ChineseAcademyofSciences [2]CorrespondencetoProfLi-heGUO [3]Children＇sHospitalofShanghaiMedicalUniversity,Shanghai200031,China

出　　处：《Acta Pharmacologica Sinica》2004年第4期490-495,共6页中国药理学报（英文版）

摘　　要：AIM: To explore the feasibility of human growth hormone (hGH) receptorantagonist in the treatment of end-stage diabetic renal complications. METHODS: Two hGH mutants,hGHA1 (Cys-hGH-dell-4, G120R, K168A, E174A, C182S, del186-191) and hGHA2 (hGH-H21A, G120R, E174A)were expressed in E coli. The IC_(50) (Mean+-SD) values for the mutants for inhibiting ^(125)I-hGHbinding to rabbit growth hormone receptor were (65+-10) ng for hGHA1, (27+-5.6) ng for hGHA2, and(10+-0.6) ng for wild type hGH, respectively. RESULTS: After treatment for 12 weeks, the renalhistology analysis showed that treatment with hGHA2 at 4 mg/kg body weight daily markedly suppressedglomerulosclerosis in streptozotocin-induced diabetic Sprague-Dawley (SD) rats; hGHA1 at the samedosage slightly increased the renal damage compared with saline; while wild type hGH at 1 U/kg bodyweight daily severely worsened the glomerulo-sclerosis in diabetic SD rats. CONCLUSION: The dataindicated that hGHA2 inhibited the end-stage glomerulosclerosis in diabetic rats, but hGHA1 mildlyincreased the glomerulosclerosis.AIM: To explore the feasibility of human growth hormone (hGH) receptorantagonist in the treatment of end-stage diabetic renal complications. METHODS: Two hGH mutants,hGHA1 (Cys-hGH-dell-4, G120R, K168A, E174A, C182S, del186-191) and hGHA2 (hGH-H21A, G120R, E174A)were expressed in E coli. The IC_(50) (Mean+-SD) values for the mutants for inhibiting ^(125)I-hGHbinding to rabbit growth hormone receptor were (65+-10) ng for hGHA1, (27+-5.6) ng for hGHA2, and(10+-0.6) ng for wild type hGH, respectively. RESULTS: After treatment for 12 weeks, the renalhistology analysis showed that treatment with hGHA2 at 4 mg/kg body weight daily markedly suppressedglomerulosclerosis in streptozotocin-induced diabetic Sprague-Dawley (SD) rats; hGHA1 at the samedosage slightly increased the renal damage compared with saline; while wild type hGH at 1 U/kg bodyweight daily severely worsened the glomerulo-sclerosis in diabetic SD rats. CONCLUSION: The dataindicated that hGHA2 inhibited the end-stage glomerulosclerosis in diabetic rats, but hGHA1 mildlyincreased the glomerulosclerosis.

关 键 词：growth hormone diabetic nephropathies MUTATION diabetes mellitus 

分 类 号：R692[医药卫生—泌尿科学] R587.2[医药卫生—外科学]