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.
Highlights
422 million people have been diagnosed with diabetes, of which, approximately 15% develop leg ulcers [1].Early treatment is the key to reducing the amputation rate in diabetic foot patients [2].Many traditional Chinese medicine (TCM) ointments effectively treat diabetic ulcers, and they show a moreEvidence-Based Complementary and Alternative Medicine significant curative effect during the early stages of treatment than in the later stages [3]
Macroscopic Evaluation Results of Traditional Chinese Medicine. e heat map of rats orally administered with 0.6 g/d for three days was presented in pink, representing Yang syndrome. e heat map of rats orally administered with 0.6 g/d for six days was presented in dark purple during the first four days, representing semi-Yin and semi-Yang (SYSY) syndrome
On termination of intragastric administration, the heat map turned red, representing Yang syndrome. e heat map of rats orally administered with 0.9 g/d for three days was presented in purple, representing SYSY syndrome. e heat map of rats orally administered with 0.9 g/d for six days became black on the 8th day, and Yin syndrome was revealed after eight days (Figure 2(a))
Summary
422 million people have been diagnosed with diabetes, of which, approximately 15% develop leg ulcers [1].Early treatment is the key to reducing the amputation rate in diabetic foot patients [2].Many traditional Chinese medicine (TCM) ointments effectively treat diabetic ulcers, and they show a moreEvidence-Based Complementary and Alternative Medicine significant curative effect during the early stages of treatment than in the later stages [3]. Many traditional Chinese medicine (TCM) ointments effectively treat diabetic ulcers, and they show a more. 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. 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. 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. CD163, CD31, IL-10, and citric acid can be used as potential specific markers for the recovery and progression of SYSY syndrome
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