PMID- 22932337
OWN - NLM
STAT- MEDLINE
DCOM- 20130905
LR  - 20131121
IS  - 0412-4081 (Print)
IS  - 0412-4081 (Linking)
VI  - 48
IP  - 5
DP  - 2012 May
TI  - [Effects of simvastatin on expression of connective tissue growth factor in 
      vitreous and retina of diabetic rats].
PG  - 444-9
AB  - 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 microg/L, 478.47 microg/L and 210.78 microg/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.
FAU - Hu, Yan-bin
AU  - Hu YB
AD  - Department of Ophthalmology, General Hospital, Tianjin Medical University, 
      Tianjin 300052, China.
FAU - Zhang, Jing-kai
AU  - Zhang JK
FAU - Sun, Zhi-yong
AU  - Sun ZY
FAU - Liu, Yu-mei
AU  - Liu YM
FAU - Yan, Hua
AU  - Yan H
LA  - chi
PT  - English Abstract
PT  - Journal Article
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PL  - China
TA  - Zhonghua Yan Ke Za Zhi
JT  - [Zhonghua yan ke za zhi] Chinese journal of ophthalmology
JID - 16210540R
RN  - 139568-91-5 (Connective Tissue Growth Factor)
RN  - AGG2FN16EV (Simvastatin)
SB  - IM
MH  - Animals
MH  - Connective Tissue Growth Factor/*metabolism
MH  - Diabetes Mellitus, Experimental/*metabolism
MH  - Diabetic Retinopathy/metabolism
MH  - Male
MH  - Rats
MH  - Rats, Wistar
MH  - Retina/metabolism
MH  - Simvastatin/*pharmacology
MH  - Vitreous Body/metabolism
EDAT- 2012/08/31 06:00
MHDA- 2013/09/06 06:00
CRDT- 2012/08/31 06:00
PHST- 2012/08/31 06:00 [entrez]
PHST- 2012/08/31 06:00 [pubmed]
PHST- 2013/09/06 06:00 [medline]
PST - ppublish
SO  - Zhonghua Yan Ke Za Zhi. 2012 May;48(5):444-9.