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

  
@article{APS8090,
	author = {Wei LI and Li-hua ZHU and En-bi WANG and Zeng-can YE and Jun LIN and Li-he GUO and Fei-hong LUO and Xi-hong LIU and Xin FANG and Shui-xian SHEN},
	title = {Effect of two human growth hormone receptor antagonists on glomerulosclerosis in streptozotocin-induced diabetic rats},
	journal = {Acta Pharmacologica Sinica},
	volume = {25},
	number = {4},
	year = {2016},
	keywords = {},
	abstract = {AIM:
To explore the feasibility of human growth hormone (hGH) receptor antagonist in the treatment of end-stage diabetic renal complications.
METHODS:
Two hGH mutants, hGHA1 (Cys-hGH-del1-4, G120R, K168A, E174A, C182S, del186-191) and hGHA2 (hGH-H21A, G120R, E174A) were expressed in E coli. The IC50 (Mean+/-SD) values for the mutants for inhibiting 125I-hGH binding 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 renal histology analysis showed that treatment with hGHA2 at 4 mg/kg body weight daily markedly suppressed glomerulosclerosis in streptozotocin-induced diabetic Sprague-Dawley (SD) rats; hGHA1 at the same dosage slightly increased the renal damage compared with saline; while wild type hGH at 1 U/kg body weight daily severely worsened the glomerulo-sclerosis in diabetic SD rats.
CONCLUSION:
The data indicated that hGHA2 inhibited the end-stage glomerulosclerosis in diabetic rats, but hGHA1 mildly increased the glomerulosclerosis.},
	issn = {1745-7254},	url = {http://www.chinaphar.com/article/view/8090}
}