Production of an Animal Model of Semi-Yin and Semi-Yang Syndrome with Diabetic Ulcers and Study of Its Pathological and Metabolic Features

Abstract

Background. To create an animal model for diabetic ulcers with semi-Yin and semi-Yang (SYSY) syndrome and to study the pathological and metabolic features of SYSY syndrome. Methods. Firstly, based on the clinical characteristics of the SYSY syndrome of diabetic ulcer, an animal model of diabetic ulcers with SYSY syndrome being full-thickness skin defects was created by injecting streptozotocin (STZ) intraperitoneally, infecting with Staphylococcus aureus, and gastrically administering senna. Secondly, the content and distribution patterns of collagen fibers, the expression of neutrophils and macrophage markers, angiogenesis, and the expression of IL-1β and IL-10 in the rats with Yang syndrome, Yin syndrome, and SYSY syndrome of diabetic ulcers at different time points were detected. Representative traditional Chinese medicine (TCM) ointment of Yang syndrome, Yin syndrome, and SYSY syndrome was used to treat this animal model. The above indexes in each treatment group were detected. Finally, metabonomics was used to detect and analyze the changes of differential metabolites related to macrophage metabolism in Yang, Yin, and SYSY syndromes at different time points. Results. An animal model of diabetic ulcers with SYSY syndrome was established. The pathological features of the SYSY syndrome group were chronic low-grade inflammatory reactions. On the third day, the SYSY syndrome group displayed lower expression of CD16, CD68, CD163, IL-1β, and metabolites related to M1-type macrophages compared with other groups. On the seventh day, the SYSY syndrome group showed lower expression of CD31, IL-10, myeloperoxidase, and metabolites related to M2-type macrophages. Treatment with Chong He Ointment, a representative TCM ointment for SYSY syndrome, reversed the expression levels of these indexes and promoted wound healing in the SYSY group. Conclusion. SYSY syndrome presents a persistent pathological state of low inflammation, which may be caused by an insufficient activation of the M1-type metabolic pathway in macrophages in the early acute inflammatory stage, resulting in the incomplete clearance of pathogens and debris and continuous stimulation of macrophages to initiate the M1-type metabolic pathway. CD163, CD31, IL-10, and citric acid can be used as potential specific markers for the recovery and progression of SYSY syndrome.

VAP-PLGA microspheres (VAP-PLGA) promote adipose-derived stem cells (ADSCs)-induced wound healing in chronic skin ulcers in mice via PI3K/Akt/HIF-1α pathway

“…Recent years have witnessed the development of chronic skin ulcers including venous leg ulcers, pressure sores and diabetic ulcers into a primary global health problem, initially appearing in the lower extremities, especially in the elderly [ 1 ]. Traditional Chinese Medicine (TCM) science categorizes ‘sore and ulcer’ into three syndromes as following: Yang syndrome, Yin syndrome (dull skin, stasis, coldness, and numbness), and semi-Yin and semi-Yang syndrome [ 2 ]. Chronic skin ulcers are considered to belong to Yin syndrome (a term in traditional Chinese medicine) skin ulcers [ 3 ].…”