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PLoS One. 2014;9(6):e98232.

The effect of lithospermic acid, an antioxidant, on development of diabetic retinopathy in spontaneously obese diabetic rats.

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제1저자 Jin CJ · 교신저자 임수

PMID 24905410 PMC4048190 DOI 10.1371/journal.pone.0098232 IF 2.8 내분비대사내과
소속 (8)
  1. Department of Internal Medicine, Seoul National University College of Medicine and Seoul National University Bundang Hospital, Seongnam, Korea; Department of Endocrinology, The ZhongShan Hospital, DaLian University, Dalian, China.
  2. Department of Internal Medicine, Seoul National University College of Medicine and Seoul National University Bundang Hospital, Seongnam, Korea; Department of Internal Medicine, Hallym University Hangang Sacred Hospital, Seoul, Korea.
  3. Department of Endocrinology, The ZhongShan Hospital, DaLian University, Dalian, China.
  4. Department of Ophthalmology, Seoul National University College of Medicine and Seoul National University Bundang Hospital, Seongnam, Korea.
  5. Department of Pathology, Seoul National University College of Medicine and Seoul National University Bundang Hospital, Seongnam, Korea.
  6. Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea.
  7. Department of Internal Medicine, Seoul National University College of Medicine and Seoul National University Bundang Hospital, Seongnam, Korea.
  8. Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea.

Abstract

BACKGROUND Lithospermic acid B (LAB), an active component isolated from Salvia miltiorrhiza radix, has been reported to have antioxidant effects. We examined the effects of LAB on the prevention of diabetic retinopathy in Otsuka Long-Evans Tokushima Fatty (OLETF) rats, an animal model of type 2 diabetes.

METHODS AND FINDINGS LAB (10 or 20 mg/kg) or normal saline were given orally once daily to 24-week-old male OLETF rats for 52 weeks. At the end of treatment, fundoscopic findings, vascular endothelial growth factor (VEGF) expression in the eyeball, VEGF levels in the ocular fluid, and any structural abnormalities in the retina were assessed. Glucose metabolism, serum levels of high-sensitivity C-reactive protein (hsCRP), monocyte chemotactic protein-1 (MCP1), and tumor necrosis factor-alpha (TNFα) and urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels were also measured. Treatment with LAB prevented vascular leakage and basement membrane thickening in retinal capillaries in a dose-dependent manner. Insulin resistance and glucose intolerance were significantly improved by LAB treatment. The levels of serum hsCRP, MCP1, TNFα, and urinary 8-OHdG were lower in the LAB-treated OLETF rats than in the controls.

CONCLUSIONS Treatment with LAB had a preventive effect on the development of diabetic retinopathy in this animal model, probably because of its antioxidative effects and anti-inflammatory effects.

Figures

Figure 1
Figure 1 Vascular leakage in fluorescein angiography in study animals. A, B: Control group. C, D: 10mg/kg LAB group. E, F: 20mg/kg LAB group. Arrows indicate vascular leakage. G: Comparison of vascular leakage among three groups. *P<0.05 vs. control group, †P<0.05 vs. 10mg/kg LAB-treated group.
Figure 2
Figure 2 Histology of the rat retina using H&E staining. A: Control retina. B: 10mg/kg LAB-treated retina. C: 20mg/kg LAB-treated retina. Key: NFL, nerve fiber layer, GCL; ganglion cell layer; IPL, inner plexiform layer; INL, inner nuclear layer; OPL, outer plexiform layer; ONL, outer nuclear layer; PRL, photoreceptor layer.
Figure 3
Figure 3 Capillaries in rat retinas and in surrounding connective tissues (× 200). A, D: Control. B, E: 10mg/kg LAB treatment. C, F: 20m/kg LAB treatment. Arrows indicate capillaries.
Figure 4
Figure 4 Immunohistochemistry for VEGF and western blot analysis of VEGF expression in the retina. A: Control group. B: 10mg/kg LAB-treated group. C: 20mg/kg LAB-treated group. *P<0.05 vs. control group, †P<0.05 vs. 10mg/kg LAB-treated group.
Figure 5
Figure 5 VEGF concentrations in ocular fluid among three groups. Each column represents mean ± SE (n = 5–6). *P<0.05 vs. control group.
Figure 6
Figure 6 Retinal capillary basement membrane thickness assessed by electron microscopy. *P<0.05 vs. control group, †P<0.05 vs. 10mg/kg LAB group.

그림 출처: PubMed Central 공개 논문 (PMC4048190)

Conflict of interest statement

Competing Interests:The authors have declared that no competing interests exist.

그 밖의 정보
출판 형태
Journal Article, Research Support, Non-U.S. Gov't
저널
PloS one · eISSN 1932-6203
전자 출판
2014-06-06
MeSH
8-Hydroxy-2'-Deoxyguanosine · Animals · Antioxidants / therapeutic use · Benzofurans / therapeutic use · C-Reactive Protein / metabolism · Chemokine CCL2 / metabolism · Deoxyguanosine / analogs & derivatives / urine · Depsides / therapeutic use · Diabetic Retinopathy / metabolism / prevention & control · Glucose / metabolism · Glucose Intolerance / drug therapy · Insulin Resistance · Male · Obesity / complications · Rats · Rats, Long-Evans · Tumor Necrosis Factor-alpha / metabolism · Vascular Endothelial Growth Factor A / metabolism
Substances
Antioxidants · Benzofurans · Chemokine CCL2 · Depsides · Tumor Necrosis Factor-alpha · Vascular Endothelial Growth Factor A · lithospermic acid · 8-Hydroxy-2'-Deoxyguanosine · C-Reactive Protein · Deoxyguanosine · Glucose
참고문헌
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