Cyclosporine-a attenuates retinal inflammation by inhibiting HMGB-1 formation in rats with type 2 diabetes mellitus

被引：11

作者：

Wang, Peng ^{[1
]}

Chen, Fei ^{[1
]}

Zhang, Xuedong ^{[1
]}

机构：

[1] Chongqing Med Univ, Chongqing Eye Inst, Affiliated Hosp 1, Dept Ophthalmol,Chongqing Key Lab Ophthalmol, 1 You Yi Rd, Chongqing 400016, Peoples R China

来源：

BMC PHARMACOLOGY & TOXICOLOGY | 2020年 / 21卷 / 01期

基金：

中国国家自然科学基金;

关键词：

Cyclosporine-a; Diabetic retinopathy; HMGB-1; Inflammation; IL-1; beta; TNF-alpha; RETINOPATHY; INTERLEUKIN-1-BETA; PATHOGENESIS; ALPHA;

D O I：

10.1186/s40360-020-0387-6

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

Background Cyclosporine-A has been regarded as an immunoregulatory and anti-inflammatory drug for the treatment of various immune inflammatory diseases. However, the effect of Cyclosporine-A on the retina of type 2 diabetic rats and the underlying mechanism remains to be elucidated. The objective of the present study was to investigate the effect and mechanism of Cyclosporine-A on diabetic retinopathy. Methods Male Sprague-Dawley rats were established to type 2 diabetic model. After 6 weeks, diabetic rats and normal controls were intravitreally injected with. Cs-A (42 ng/2 mu L) to the left eye, and 2 mu L DMSO to the right eye for the control.. Another group of normal wild-type rats was subjected to intravitreal injections into. The left eyes with 5 mu L PBS or HMGB-1 (5 ng/5 mu L) or HMGB-1(5 ng/5 mu L) plus. Cs-A (42 ng/2 mu L), respectively. Retinal morphological changes were observed with. Hematoxylin-eosin staining. Expressions of HMGB-1, IL-1 beta and TNF-alpha were. Detected by immunohistochemistry, ELISA or Western blot or RT-PCR. Results Retinal expression levels of IL-1 beta and TNF-alpha were upregulated in type 2. diabetic rats and in normal rats with intravitreal injection of HMGB-1, which were. Attenuated by intravitreal Cs-A. Moreover, Cs-A decreased HMGB-1 expression in. diabetic retina and relieved the retinopathy in type 2 diabetic rats. Conclusions Intravitreal administration of Cs-A showed a protective effect on retina. of diabetic rats, possibly by downregulating retinal expressions of IL-1 beta and TNF-alpha. via the suppression of HMGB-1.

引用

页数：7