• Mengjun Xie, Liping Deng, Yueting Yu, Xuejun Xie, and Mei Zhang.
• School of Pharmacy, Chengdu University of Traditional Chinese Medicine, No. 1166 Liutai Avenue, Wenjiang District, Chengdu, Sichuan, 611137, PR China. Electronic address: xiemengjun@stu.cdutcm.edu.cn.
• Biomed. Pharmacother. 2021 Jan 1; 133: 110920.

BackgroundDiabetic retinopathy (DR) is one of the most serious complications in the late stages of diabetes, with a complex mechanism. As a complication affecting local lesions, few studies have compared differences of cytokine expression in the serum and retina. Owing to the specific value of traditional Chinese medicine (TCM) to complex diseases, TCM research has recently boomed in the prevention and treatment of diabetes. Bushen Yiqi Huoxue (BYH) prescription is a Chinese herbal compound that has been independently developed by our research group and has been proved to have a positive effect on DR; however, its specific mechanism and compatibility rule remain to be further explored.ObjectiveTo construct a DR model of Sprague Dawley (SD) rats, simultaneously detect multiple factor expression in the serum and retina of rats, explore the effect of BYH prescription and its disassembled prescriptions on DR, and discuss the influence of various compatibility combinations.MethodsBYH prescription was disassembled into two new compatibilities in the absence of Rehmanniae Radix (Yiqi Huoxue prescription, YH prescription) or Ginseng Radix et Rhizoma (Bushen Huoxue prescription, BH prescription). Male SD rats were induced using streptozotocin + high-fat and high-sugar diet to establish DR models and were divided into groups, then the intragastric administration and sampling. The body weight and fasting blood glucose of rats were continuously recorded during feeding; pathophysiological status observation of the retina by haematoxylin and eosin (HE) staining; advanced glycation end products (AGEs) and haemoglobin A1c (HbA1c) level detection in the rat serum by enzyme-linked immunosorbent assay; and the Luminex technique was used to detect the ICAM-1, IL-1β, IL-6, TNF-α and vascular endothelial growth factor (VEGF) expression concentrations in the retinal tissue and serum.ResultsThe results of blood glucose, body weight and HE staining proved that the model was successfully constructed, and the three combinations could reduce the retinal injury in DR rats. Serum AGEs and HbA1c levels of the model group increased compared with the control group (CG). Compared with the DR model group, only AGEs decreased in the BYH group, while the AGEs and HbA1c levels were significantly inhibited in the YH and BH groups, showing a significant correlation between the expression of AGEs and HbA1c in the serum of DR rats. In the serum of rats, IL-1β, IL-6, TNF-α and VEGF concentrations in the DR model group increased, although no statistical difference was observed in the ICAM-1 data compared with the CG. Compared with the DR model group, the IL-1β, IL-6 and TNF-α expression decreased in the BYH group. Moreover, the IL-6 and TNF-α expression decreased in the YH group and only the IL-6 expression decreased in the BH group. In the retina tissue, the model group had higher ICAM-1, IL-1β, IL-6, TNF-α and VEGF levels than the CG. Compared with the DR model group, TNF-α in the BYH group rats decreased, and the ICAM-1, IL-6 and TNF-α concentrations decreased in the YH and BH groups. Furthermore, differences in the ICAM-1 and VEGF expression in the serum and retina existed.ConclusionBYH compound and its disassembled prescriptions could improve the DR model rats induced with streptozotocin + high-fat and high-sugar diet, respectively, by inhibiting chronic blood glucose, AGEs, or inflammation response. The expression level and location of each factor are different, confirming that the effect of TCM prescriptions is not the simple addition of each single drug or its chemical components, but the rationality of its internal compatibility combination. Further, ICAM-1 and VEGF have exactly different expression levels, suggesting more attention to be paid by other researchers or doctors in future studies.Copyright © 2020 The Authors. Published by Elsevier Masson SAS.. All rights reserved.

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