The effect of spleen tyrosine kinase inhibitor R406 on diabetic retinopathy in experimental diabetic rats
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ORIGINAL PAPER
The effect of spleen tyrosine kinase inhibitor R406 on diabetic retinopathy in experimental diabetic rats Xian Su . Zhao-Hui Sun . Qian Ren . Jun-Ru Liu . Li Yin . Na Liang . Ling Meng . Rui-Xue Sun
Received: 20 February 2020 / Accepted: 11 May 2020 Ó Springer Nature B.V. 2020
Abstract Purpose To investigate the effect of spleen tyrosine kinase (Syk) inhibitor R406 on diabetic retinopathy (DR) in diabetic mellitus (DM) rats. Methods Rats were randomized into Normal, DM, DM ? 5 mg/kg R406 and DM ? 10 mg/kg R406 groups. DM rats were established via injection of streptozotocin (STZ). One week after model establishment, rats in treatment groups received 5 mg/kg or 10 mg/kg R406 by gavage administration for 12 weeks consecutively, followed by the detection with hematoxylin-eosin (HE) staining, Evans blue angiography, retinal trypsin digestion assay, Western blotting, immunohistochemistry, TUNEL assay, immunofluorescence assay and quantitative reverse transcriptase real-time polymerase chain reaction (qRT-PCR). Results The retina of DM rats presented different degree of edema, disordered and loose structure,
swollen cells with enlarged intercellular space, and dilated and congested capillaries. Besides, the retinal vessels of DM rats showed high fluorescence leakage. However, R406 alleviated the above-mentioned conditions, which was much better with high concentration of R406 (10 mg/kg). R406 also reversed the down-regulations of occludin, claudin-5, ZO-1 and the up-regulation of and VEGF in retinal tissues of DM rats; inhibited retinal cell apoptosis; strengthened retinal cell proliferation; and reduced expressions of IL-1b, IL-6, TNF-a and nuclear p65 NF-jB in retinal tissues. The improvement in all these indexes was much more significant in rats of DM ? 10 mg/kg R406 group than in rats of DM ? 5 mg/kg R406 group. Conclusion Syk inhibitor R406 could attenuate retinal inflammation in DR rats via the repression of NF-jB activation. Keywords Diabetic retinopathy Spleen tyrosine kinase R406 NF-jB
X. Su Z.-H. Sun Q. Ren L. Yin N. Liang L. Meng R.-X. Sun (&) Department of Ophthalmology, The First Hospital of Shijiazhuang City, No. 12, Pingan North Street, Shijiazhuang 050000, Hebei Province, China e-mail: [email protected] J.-R. Liu Department of Ophthalmology, The Third Hospital of Shijiazhuang City, Shijiazhuang 050011, Hebei Province, China
Introduction As we know, diabetic mellitus (DM) is one of the most common chronic diseases mainly caused by insufficient insulin synthesis or insulin dysfunction, with the characteristics of metabolic disorder of carbohydrates,
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lipids and proteins [1]. In recent years, we have witnessed the sharp increase in DM patients worldwide, and its prevalence rate would be estimated to reach up to 550 million by 2030 [2]. Generally, longterm hyperglycemia may lead to microvascular diseases in DM and induce the occurrence of various relevant complications, while diabetic retinopathy (DR),
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