title: [Effects of simvastatin on expression of connective tissue growth factor in vitreous and retina of diabetic rats].
abstract: OBJECTIVE
  To study the effects of simvastatin on the expression of connective tissue growth factor (CTGF) that cause fibrosis in the vitreous and retina after intravitreal injection in diabetic rats, and to explore the safety of this procedure.
  
  
  METHODS
  It was an experimental study. Forty adult male Wistar rats were randomly divided into normal control group (10 rats) and diabetes mellitus group (30 rats). Four months later, according to whether treated with simvastatin or not, the diabetes mellitus group randomly divided into simvastatin intervention group (20 rats) and diabetic positive control group (10 rats). Simvastatin was injected into the vitreous in the simvastatin intervention group, but not in the diabetic positive control group. Seven days later, after the examination of electroretinogram (ERG), all rats were sacrificed, and their eyeballs were enucleated. Enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry method were performed to determine the expression of CTGF in the vitreous and retina. Terminal DNA transferase-mediated dUTP nick end labeling (TUNEL) method was used to detect apoptosis of retina cells. Concentration of CTGF in the vitreous, retinal expression of CTGF, retinal cellular apoptosis index, ERG-b wave and oscillatory potentials (OPs) of rats in each group were compared using analysis of variance LSD test methods.
  
  
  RESULTS
  No systemic toxic reactions, no lens opacity and no endophthalmitis occurred after injection of simvastatin into the vitreous of rats. Concentrations of CTGF in vitreous of simvastatin intervention group, diabetes positive control group and normal control group rats were 359.21 µg/L, 478.47 µg/L and 210.78 µg/L, respectively (F = 252.366, P < 0.05). The levels of CTGF in the vitreous of simvastatin intervention group and diabetic positive control group was significantly higher than that of the normal control group and showed significant difference (t = 12.123, 23.816;P < 0.05). CTGF levels in simvastatin intervention group were significantly lower than those in diabetic positive control group, and the difference was statistically significant. (t = 11.693, P < 0.05). The results of immunohistochemical staining and TUNEL staining were negative in the normal control group. Retinal expression of CTGF in simvastatin intervention group and diabetic positive control group were (26.60 ± 2.95)% and (42.31 ± 2.59)%, respectively. Retinal expression of CTGF in simvastatin intervention group was reduced as compared to the diabetic positive control group, the difference was statistically significant (t = 12.112, P < 0.05). Retinal cellular apoptosis index of simvastatin intervention group and diabetic positive control group was 0.19 ± 0.02 and 0.25 ± 0.03, respectively. Retinal cellular apoptosis index of simvastatin intervention group was significantly lower than that in diabetic positive control group (t = 4.745, P < 0.05). ERG revealed no significant changes. In simvastatin intervention group as compared with diabetic positive control group.
  
  
  CONCLUSIONS
  Simvastatin could inhibit the expression of CTGF in the vitreous body and retina in diabetic rats. Intravitreal injection of simvastatin is a relatively safe procedure.
authors.affiliation: Department of Ophthalmology, General Hospital, Tianjin Medical University, Tianjin 300052, China.
authors.forename: Yan-bin
authors.initials: YB
authors.lastname: Hu
authors.forename: Jing-kai
authors.initials: JK
authors.lastname: Zhang
authors.forename: Zhi-yong
authors.initials: ZY
authors.lastname: Sun
authors.forename: Yu-mei
authors.initials: YM
authors.lastname: Liu
authors.forename: Hua
authors.initials: H
authors.lastname: Yan
mesh_terms: D000818:Animals; D055513:Connective Tissue Growth Factor / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D003930:Diabetic Retinopathy / Q000378:metabolism; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D012160:Retina / Q000378:metabolism; D019821:Simvastatin / Q000494:pharmacology*; D014822:Vitreous Body / Q000378:metabolism
chemical_list: D055513:Connective Tissue Growth Factor; D019821:Simvastatin