ABSTRACT
The long-term existence of hyperglycemia leads to the occurrence of metabolic memory effect， which is an important reason for the formation of diabetic macrovascular disease， so the early control of metabolic memory is the key to the prevention and treatment of diabetes and its complications. The excessive formation of advanced glycation end products （AGEs） is not only an important factor to cause metabolic memory， but also the core mechanism for diabetic macrovascular disease. It is believed in traditional Chinese medicine（TCM） that Fu-xie （incubative pathogen） is the key pathogenesis of the formation of diabetic vascular diseases， and it is necessary to adopt the principle of removing pathogenic factors and opening collaterals as early as possible to prevent and cure the disease. During the Spring and Autumn Period and the Warring States Period， the theory of Fu-xie was germinated， and got mature in the Ming and Qing dynasties after the continuous development. The so-called Fu-xie means that the pathogens are of a potential nature but not cause diseases immediately. The theory of Fu-xie first appeared in Huangdi Neijing， with an original meaning of epidemic febrile disease occurring after incubation， and then its meaning continues to expand， now referring to all potential pathogenic factors that would not immediately cause diseases. As the cause and pathogenesis of many diseases， the theory of Fu-xie is widely used in clinical practice to guide the treatment of diseases. In the body， the accumulation of AEGs can induce the subsequent cascade effect in the body， and finally promote the formation and development of diabetic macrovascular diseases. This is very similar to the process of inducing metabolic disorder and disease in TCM due to the accumulation of phlegm and silt. Therefore， under the guidance of Fu-xie theory， the mechanism of AEGs in blocking metabolic memory and preventing and treating diabetic macrovascular disease was analyzed in this paper. On the one hand， it will provide a scientific basis for the exploration of Fu-xie theory affecting the disease course of diabetic macrovascular disease by regulating the generation of AEGs. On the other hand， it can also provide the material change basis for the development of Fu-xie theory in the occurrence and development of diabetic macroangiopathy.
ABSTRACT
This study was aimed to investigate the mechanism of Danzhi Jiangtang Capsules( DJC) in the treatment of diabetic macrovascular disease in Goto-Kakizaki( GK) rats. The diabetic macrovascular disease rat model was induced by feeding high-fat and high-sugar combined with endothelial nitric oxide synthase( NOS) inhibitor N-nitro-L-arginine methyl ester( L-NAME)( 0. 1 g·L-1·d-1). According to the random array table,the model rats were randomly divided into the model group,DJC groups( 1 260,630,320 mg·kg-1),atorvastatin group( 105 mg·kg-1) and metformin group( 10 mg·kg-1),with 12 rats in each group. The rats received gavage administration for 8 weeks. Twelve Wistar rats were selected as the normal control group. The changes of body weight,water intake,blood glucose,plasma total cholesterol( TC),triglyceride( TG),high density lipoprotein( HDL-C),low density lipoprotein( LDL-C),interleukin( IL-1β),IL-6,tumor necrosis factor( TNF-α),nitric oxide( NO),endothelin( ET-1) were observed in these rats. Aortic tissue was taken and the pathological changes were observed by HE staining. RT-PCR was used to detect the mRNA levels of IL-1β,IL-6,and TNF-α in rat aorta. RT-PCR of the stem loop was used to detect the levels of miRNA-126,miRNA-155,miRNA-146 a,and miRNA-21 in rat plasma and aortic tissue. The canonical correlation between miRNAs and inflammatory factors was then analyzed. The results showed that DJC increased the rat body weight,lowered water intake,reduced the random blood glucose,reversed the rat aorta tissue damage,reduced serum TC,TG,LDL-C,ET-1,IL-1β,IL-6,TNF-α,as well as miRNA-155,miRNA-146 a and miRNA-21 levels in serum,elevated plasma HDL-C,NO content,reduced the aorta mRNA of IL-1β,IL-6,TNF-α,and the miRNA-155,miRNA-146 a and miRNA-21,elevated miRNA-126 expression in aorta. Aortic miRNA-126,miRNA-155,miRNA-146 a and miRNA-21 expression levels were typically correlated with the expression of inflammatory factors,among which miRNA-126 was negatively correlated,miRNA-155,miRNA-146 a and miRNA-21 were positively correlated with the factors. These results suggested that DJC had therapeutic effects on diabetic macrovascular diseases,and the mechanism of action may be related to the regulation of miRNA-126,miRNA-155,miRNA-146 a and miRNA-21 levels,as well as the reduction of inflammatory factors and vascular inflammatory response.