OBJECTIVE: To investigate the relevance of blood activation and blood stasis method in the treatment of diabetic nephropathy. METHODS: To summarize, count and analyze the research progress of the method of activating blood circulation and removing blood stasis in the treatment of diabetic nephropathy in recent years. RESULTS: The treatment of diabetic nephropathy with the method of activating blood circulation and removing blood stasis can achieve good clinical efficacy. CONCLUSION: DN has hemodynamic changes at an early stage. In the treatment, the method of activating blood circulation and resolving blood stasis should be used throughout. Keywords: diabetic nephropathy; blood activation and stasis; blood stasis evidence Preface Diabetic nephropathy (DN) is a specific kidney damage caused by diabetes mellitus and is one of the common and serious complications of diabetes mellitus (DM). With the change of people’s living habits and other factors, the incidence of DM and DN in China is rapidly increasing. DN without active prevention and treatment eventually progresses to end-stage renal disease (ESRD). To date, the pathogenesis of DN is not fully understood. The treatment is still based on hypoglycemia, lipid regulation, rational diet and symptomatic treatment with ACEI and ARB, but the results are not significant, while Chinese medicine has a long history of treating this disease and has accumulated rich experience. In particular, the treatment of activating blood circulation and resolving blood stasis has been achieved. The research progress of DN treatment by activating blood circulation and resolving blood stasis in recent years is reviewed as follows. 1.1 DN belongs to “thirst”, “edema”, “guange”, “lumbago”, “lumbago” and “lumbago” in traditional Chinese medicine. The formation of DN is believed to be due to deficiency of endowment, alcohol and thick food, and injury caused by emotion and room strain, resulting in deficiency of essence and qi, resulting in yin deficiency and internal heat, and kidney deficiency and water flooding. Therefore, the pathological nature of the disease is based on the deficiency of both qi and yin, the deficiency of essence, and the deficiency of both yin and yang as the original deficiency, and the internal growth of dryness and heat, the retention of water and dampness, and the internal accumulation of dampness and turbidity as the standard reality, which is always the original deficiency and the standard reality. In the early stage, the deficiency of qi and fluid and the deficiency of spleen and kidney are the main causes. With the development of the disease, the deficiency of yin and dry heat injures the blood, and the deficiency of qi and blood stagnates into stasis, then there are pathological products such as blood stasis, water-dampness and phlegm turbidity. With the prolongation of the disease, it gradually develops to the advanced stage, with Qi and Yin deficiency, Yin and Yang deficiency, kidney deficiency, blood stasis and water flooding being the most common. Chinese medicine believes that the long duration of DN disease, long illness injures yin and consumes qi, deficiency of qi and yang is weak, unable to warm the blood vessels and blood flow is unfavorable, which can lead to stasis of veins and veins and internal stagnation of blood. According to the traditional theory of pathology, “prolonged disease will lead to deficiency, prolonged disease will lead to kidney disease, and prolonged disease will lead to luo” is fully reflected in DN. DN is based on the deficiency of kidney energy and is accompanied by the pathological process of blood stasis, presenting symptoms of multiple deficiencies and blood stasis. 1.2 Numerous medical scholars have made numerous observations and studies on the pathogenesis of DN: Huang Yanqin and Guo Dengzhou considered blood stasis as an important pathogenesis in the early stage of DN. In the early and middle stages of DN, the basic pathomechanism is stasis of blood and accumulation of obstruction. Wu Fan and Cao Hui suggested that the early mechanism of DN is based on yin deficiency and blood stasis, manifesting as deficiency of liver and kidney qi and yin, accompanied by internal obstruction of blood stasis and occlusion of veins and ligaments, and treatment must focus on activating blood and resolving blood stasis. According to Lu Renhe and Dai Jingzhang, DN is located in the “luo” of the kidney; the pathology is “luo-vessel Y obstruction”. The process of phlegm, heat, stagnation and stasis intermingling and blocking the ligaments, forming miniature Y obstruction, and the gradual formation of Y obstruction from Y obstruction to Y node. Wu Yiling discussed the pathological mechanism of DN from the theory of ligament pathology and concluded that “stagnation of ligaments and blood vessels and accumulation of phlegm” is the main pathological link, and “accumulation of kidney ligaments” is the main pathological change as well as the key factor for its development and aggravation. Zhao Jinxi and Li Lei divided the course of the disease into three stages: early, middle and late, each of which is accompanied by stasis of the ligaments and veins, and the treatment principle is to remove stasis and open the ligaments throughout. In addition, many physicians believe that blood stasis exists in the whole process of DN and that ligament stasis is the main pathological link of diabetic nephropathy, and advocate the method of activating blood stasis as an important rule in the treatment of DN. 1.3 In an overview of the pathogenesis of DN, Chinese medicine is characterized by the main pathology of blood stasis blocking the kidney ligaments. Although there is a lack of uniformity in the TCM typology of DN, many experts, based on the clinical symptoms of DN, also recognize that DN with Qi deficiency and Blood stasis is more common, and therefore medical practitioners mostly emphasize factors such as Qi and Blood, ligaments and stasis. The mechanism of blood stasis is that in the early stage of thirst, dryness and heat injure the fluid, which leads to stasis due to fluid deficiency and blood deficiency; secondly, qi deficiency and weakness in pushing, which leads to slow blood flow and stagnation; thirdly, yang deficiency and cold clotting, which leads to cold clotting and blood stasis; fourthly, the condition is lingering and difficult to heal, and the disease enters the luo for a long time, i.e. “the disease is long and deep, and the yingwei line is astringent”. The pathological process of “stasis” is both the causative factor and the pathological product, and the result of stasis causing stasis in the veins and ligaments and poor blood flow makes the stasis more significant, which in turn aggravates the kidney damage, thus forming a vicious circle, leading to recurrent clinical symptoms and eventually becoming a persistent disease difficult to treat. 2.Modern medical theory of blood stasis Modern medicine believes that DN patients have hyperlipidemia and hyperviscosity, and there are obvious local disorders of glomerular microcirculation and coagulation mechanism, which slow down renal blood flow, increase aggregation of red blood cells, and cause a large number of platelets with high activity to enter the blood circulation, resulting in elevated platelet adhesion and aggregation, and a large number of blood cells aggregation, which easily lead to microthrombus formation in glomeruli and tubules, making the glomerular filtration membrane This will increase the permeability of the glomerular filtration membrane, increase the matrix, produce or aggravate proteinuria, promote glomerulosclerosis, and accelerate the development of DN. Meanwhile, long-term hyperglycemia damages the vascular endothelial system, and the release of inflammatory factors and cytokines triggers vasculopathy, which aggravates renal blood stasis and worsens with the progression and prolongation of the disease. Jiao believes that the pathological mechanism of increased blood viscosity and microcirculatory disorders in modern medicine is similar to the basic pathological mechanism of Chinese medicine: “deficiency of both qi and yin and phlegm obstruction in the veins and ligaments”. At present, the mechanism of blood stasis has not yet been explained, but as modern medicine continues to conduct in-depth research, blood stasis in TCM will no longer be a mystery, and will provide more reliable clinical targets for diagnosis and treatment. The mechanism of blood stasis activation and elimination method The blood stasis activation and elimination method refers to the treatment method of blood circulation, promoting blood flow and dissipating blood stasis. By repairing the damage of vascular endothelial cells and inhibiting their proliferation, the method can effectively improve the state of “blood stasis” due to tissue ischemia and hypoxia, thus interfering with blood vessel renewal and preventing the development of disease. In addition, the blood stasis activation method can also promote angiogenesis, mainly by promoting the establishment of collateral circulation and improving blood supply and organ function at the lesion site. Wang Ruoguang et al. conducted an in-depth study on the relationship between blood stasis and microcirculation, and concluded that the imbalance of dynamic balance between meridians (blood vessels) and blood is the root cause of blood stasis, which is not only inhibited by microcirculatory function, but also hyperfunctional; their study showed that many blood-stasis-activating drugs have two-way effects, i.e., different effects of stopping and moving blood, depending on the dose, which means that the blood-stasis-activating method has both inhibiting (stopping blood) and protecting (moving blood) effects. The method of activating blood circulation and removing blood stasis has both inhibitory (hemostasis) and protective (blood circulation) angiogenic effects in both directions. The method of activating blood circulation and removing blood stasis can reduce glomerular capillary basement membrane thickening and glomerular thylakoid cell hyperplasia, thylakoid stroma increase and thylakoid area widening, which has a complex pathophysiological mechanism of multi-pathway and multi-link interaction, interfering with DN disease progression. The mechanisms of activating blood circulation and blood stasis therapy and activating blood stasis drugs against DN may include: lowering blood sugar, correcting lipid metabolism disorders, improving microcirculation, controlling blood pressure, lowering glomerular hyperfiltration, lowering inflammatory factors, regulating cytokines, and regulating immunity. In addition, blood activation and blood stasis treatment and blood stasis activation drugs also exist to directly or indirectly delay the progression of DN and protect renal function by mechanisms that have not yet been elucidated. 2. Clinical studies on activating blood circulation and removing blood stasis method 2.1 Zhou Hui et al. improved glomerular hyperfiltration state. The mechanism may be related to the improvement of lipid metabolism and blood rheology to improve the filtration and reabsorption function of glomerular basement membrane. 2.2 Huang Yanqin et al. used the method of invigorating blood and promoting blood circulation, adding Zeilan, Ghost Arrow, Danshen and Water Frog to invigorate blood circulation and resolve blood stasis, in order to eliminate the symptoms of blood stasis and toxicity; Mudanpi clears heat and cools the blood, and cooked rhubarb removes blood stasis and clears heat, and the above drugs together resolve the toxicity of phlegm, dampness, stasis and heat, as adjuvants. The whole scorpion is good at walking, detoxifying and invigorating the blood, so as to move the potential of the drug, and is the making drug. The method of tonifying the kidney, invigorating blood and promoting blood circulation has a good preventive effect on early DN. 2.3 Guo Dengzhou et al. treated DN when to activate blood circulation, eliminate blood stasis, eliminate Y and pass the ligaments, with the proposed Chinese medicine compound preparation (composed of Di Long, Turtle A, Dan Shen, Rhubarb and Huang Qi. In the formula, Di Long and Soft-shelled turtle nail promote blood circulation and blood circulation, softening and dispersing Y nodules as the ruler) have achieved good clinical efficacy in the treatment of early and middle DN. 2.4 Yang Nezhi emphasized early diagnosis and early treatment, timely adoption of TCM Yi Qi and Blood Activation method with additional treatment to intercept the disease and delay or even reverse the progression of diabetic nephropathy. 2.5 Fan Xin applied Yi Qi, tonifying the Kidney and invigorating the Blood to 68 diagnosed DN patients for clinical observation and treatment, and concluded that Yi Qi, tonifying the Kidney and invigorating the Blood has good therapeutic effect on DN patients and is worthy of clinical promotion. 2.6 Yuan Fei et al. treated early DN patients with the formula of strengthening the spleen, tonifying the kidney and invigorating blood on the basis of Western medical treatment, which could more obviously reduce proteinuria and improve clinical symptoms, thus delaying the process of renal decompensation. 2.7 Chen Zhigang and Ye Renzhan combined the use of Qi-enhancing, Blood-boosting and Kidney-supplementing herbs on top of conventional Western medicine treatment, which significantly improved the efficacy. 2.8 Hu Gu Bing’s method of tonifying the kidneys and talking about blood was effective in improving kidney function and reducing urine protein, which is worthy of clinical promotion. A large number of clinical and experimental studies have also shown that activating blood circulation and resolving blood stasis can improve the clinical efficacy of DN and reduce renal pathological damage. In summary, blood stasis pathological changes exist in the early stage of thirst and continue throughout its development. Blood stasis is not only a pathological product, but also influences the developmental changes and regression of DN. Once blood stasis is formed, it leads to microcirculatory disorders, microvascular dysregulation, and microenvironmental disorders, which aggravate the disease and make it difficult to heal, and in turn aggravate the development and evolution of DN, forming a vicious circle. Therefore, the active use of blood activation and blood stasis remedies can prevent DN and its complications by improving microcirculation, regulating body metabolism and anti-oxidation. In recent years, with the in-depth research on the pharmacology of modern traditional Chinese medicine (blood-activating drugs) in the pathogenesis of DN, many experts and scholars have paid attention to the identification and treatment of Chinese medicine, and have conducted more extensive and in-depth research and demonstration in activating blood circulation and removing blood stasis, and have achieved some results. Compared with western medicine, traditional Chinese medicine treatment of DN by activating blood circulation and removing blood stasis works through multiple links and pathways, and also has the unique advantages of flexible addition and reduction of formulae and less side effects, especially in the early and middle stages with better efficacy. If the basic, clinical and experimental aspects can be linked together scientifically and organically, and new technologies and methods can be fully utilized, the role of blood activating and stasis-transforming drugs can be understood from multiple angles and levels and the role and mechanism of blood activating and stasis-transforming drugs in the prevention and treatment of DN can be elaborated more deeply, and the level of blood activating and stasis-transforming drugs in the prevention and treatment of DN can be improved.