Intervention of chronic renal failure disease by laxative method to dispel blood stasis

Chronic kidney disease (chronic kidney disease CKD) in the global incidence has been showing an upward trend, has become the world’s most concerned about one of the public health problems. 2007 published by the U.S. National Institutes of Health supported by a U.S. Health and Nutrition Examination Survey (NHANES) 1999-2004 analysis of the results showed that in the United States CKD is a disease is increasing. CKD is a growing disease in the United States. The prevalence of CKD in urban and rural populations over 18 years of age in Beijing, China is 13%, and CKD, if not effectively controlled, will eventually develop into Chronic Renal Failure (CRF). According to statistics, the number of dialysis patients due to chronic renal failure has been increasing worldwide: 426,000 in 1990, 1,065,000 in 2000, and is expected to reach more than 2 million in 2010, but developing countries, which account for 80% of the world’s population, have a higher prevalence of CKD. However, developing and underdeveloped countries, which account for 80% of the global population, account for 10% of the dialysis population, and the majority of patients with end-stage renal failure in these countries do not have access to dialysis treatment. In China, according to an incomplete survey in two major cities, Beijing and Shanghai, the number of new patients entering hemodialysis is around 4,000 cases every year. Meanwhile, although dialysis and transplantation can save patients’ lives and improve their quality of life, patients and their families, as well as the society, have to bear huge medical expenses regardless of dialysis or kidney transplantation. In China, there are still many uremic patients who do not have access to timely dialysis, and even fewer who can receive a kidney transplant. Especially in rural and western areas, patients still cannot get dialysis and transplantation treatment and die of uremia. Therefore, it has become a daunting task for medical workers to actively explore the non-replacement therapy of CRF, to alleviate the pain of patients, and to relieve the heavy burden of high treatment costs on families and society. Chronic renal failure can be developed from a variety of illnesses, the disease process is long, the pathogenesis is complex, both the depletion of positive qi, but also the real evil impediment, is a deficiency of the standard, mixed evidence of deficiency and reality. It is important to differentiate between the symptoms of the disease and the deficiency of the underlying principle, and the severity of the deficiency of the positive and the evil for evidence-based treatment. After years of clinical accumulation, this group summarizes that the main pathogenesis of chronic renal failure is spleen and kidney deficiency, turbid and stasis obstruction, according to which strengthening the spleen and tonifying the kidneys, eliminating turbid and stasis as the treatment principle, and formulates the Dispel Toxin Granules. Through clinical and experimental research, this study elucidated the efficacy and mechanism of Chinese medicine spleen and kidney tonifying, turbidity and stasis eliminating method in the treatment of CRF at the level of molecular biology, and confirmed that the method of spleen and kidney tonifying, turbidity and stasis eliminating method has the effect of anti-renal interstitial fibrosis and anti-glomerular sclerosis, and it can intervene in the long term (1-6 years) course of chronic renal failure and slow down the progression of chronic renal failure, and provide an effective method for the traditional Chinese medicine treatment of this disease. This subject achieves the expected purpose. I. Experimental study 1. Intervention effect of expectorant granules on renal interstitial fibrosis in rats with unilateral ureteral obstruction Objective: To observe the intervention effect of expectorant granules on renal interstitial fibrosis in rats with unilateral ureteral obstruction (UUO) and to explore the mechanism of its action. METHODS: Ninety male Wistar rats were randomly divided into five groups: sham operation group, model group, urotoxin clear group (control group), expectorant pellet low-dose group (low-dose group), expectorant pellet high-dose group (high-dose group), 18 rats in each group, except for the sham operation group, the rest of the groups were used to establish an animal model of interstitial fibrosis by the method of unilateral ureteral obstruction (UUO), and the groups were given the corresponding concentration and dose of drugs from the first day of the pre-operative period. The rats were put to death in batches at 3d, 7d and 14d after the operation, and the changes of urinary N-acetyl-β-glucosaminidase (NAG), blood creatinine (Scr) and urea nitrogen (BUN) were detected, and the renal tissues on the side of the infarct were subjected to HE staining and Masson staining, which was used for the observation of renal histopathological changes and semi-quantitatively calculation of tubulointerstitial injury index (TII). HE staining was used to observe the pathological changes of renal tissue and semi-quantitatively calculate the tubulointerstitial injury index (TII), Masson staining was used to determine the collagen area of the renal interstitium, and immunohistochemistry was used to detect the expression of connective tissue growth factor (CTGF), collagen type I (ColI), hepatocyte growth factor (HGF), and bone-forming protein (BMP)-7 in the renal tissues. RESULTS: Compared with the model and control groups, expectorant granules significantly reduced urinary NAG enzyme, Scr, and BUN in UUO rats at 14 days postoperatively (P<0.05); HE staining of renal tissues of the infarcted side for TII scoring revealed that the tubular injury index of rats in the 2 test groups was lower than that of the model and control groups at different time points (P<0.05-0.01); Masson staining to determine the renal interstitial collagen area, the renal interstitial collagen area of rats in the 2 experimental groups was less than that of the model and control groups (P<0.05~0.01); immunohistochemical staining method revealed that the expression of CTGF and ColI in renal tissues of rats in the 2 experimental groups was down-regulated in the 2 experimental groups compared with that of the model and control groups (P<0.05), and the expression of HGF and BMP-7 in renal tissues was up-regulated (P<0.05). CONCLUSION: Dispelling granules have the effect of improving renal interstitial fibrosis, and the mechanism may be related to the down-regulation of the expression of fibrogenic factors CTGF and ColI in the kidneys and the up-regulation of the expression of anti-fibrogenic factors HGF and BMP-7 in the kidneys of UUO rats. 2.Effects of expectorant granules on the ultrastructure of MMP-2, TIMP-2, ECM and podocytes in renal cortex of 5/6 nephrectomized rats Objective: To observe the effects of expectorant granules on matrix metalloproteinase-2 (MMP-2) and tissue inhibitor of metalloproteinase-2 (Tissue inhibitor of metalloproteinase-2) in renal cortex of 5/6 nephrectomized rats. The effects of matrix metalloproteinase-2 (MMP-2) and tissue inhibitor of metalloproteinase-2 (TIMP-2) protein expression, extracellular matrix (ECM) accumulation and ultrastructure of podocytes were investigated. METHODS: The 55 Wistar rats were randomly taken into 10 normal control groups, and the remaining 5/6 nephrectomy method was used to establish an animal model of chronic renal failure (CRF), and the rats were randomly divided into the model group, the urethane pellet group (referred to as the control group), the elimination pellet low dose group (referred to as the low-dose group) and the elimination pellet high-dose group (referred to as the high-dose group), with 10 rats in each group. Each group of 10 rats was given the corresponding concentration and dosage of drugs, and the urinary protein and renal function of the rats were measured during the experimental period, and the pathological changes of the kidneys were observed after 12 weeks of treatment, the degree of glomerulosclerosis was evaluated by PAS staining, the expression of glomerular collagen type IV (ColIV), fibronectin (FN), and MMP-2 and TIMP-2 were detected by immunohistochemistry, and ultrastructure of the podocytes was observed by electron microscopy. RESULTS: The expectorant granules significantly reduced the amount of urinary protein in 5/6 nephrectomized rats (P < 0.05), improved renal function, and alleviated the pathological damage of kidney; PAS staining showed that the ratio of glomerular positive area to total glomerular area and the glomerulosclerosis index were significantly decreased after treatment with expectorant granules (P<0.01); immunohistochemistry showed that expectorant granules suppressed the expression of FN, ColIV, FN, FN, and TIMP-2 proteins in renal tissues (P<0.01); immunohistochemistry showed that expectorant granules inhibited FN and ColIV expression in renal tissues (P<0.01). Immunohistochemical examination showed that Dispelling granules inhibited the expression of FN and ColIV in renal tissues (P<0.01), down-regulated the expression of TIMP-2 protein, increased the activity of MMP-2, and reduced the accumulation of ECM; electron microscopy showed that Dispelling granules reduced the detachment of podocytes, alleviated the fusion of pedicle protrusions, and protected the morphology of podocytes. Conclusion: By adjusting the expression of MMP-2 and TIMP-2 in the renal cortex of 5/6 nephrectomized rats, Dispelling granules can promote the degradation of ECM, reduce the accumulation of ECM, protect the podocytes and alleviate the effect of glomerulosclerosis. Clinical research 1, expectorant particles in the treatment of chronic renal failure clinical research Objective: to observe the clinical efficacy of expectorant particles in the treatment of chronic renal failure (Chronic Renal Failure, CRF). Methods: CRF patients with Chinese medicine diagnosis of spleen and kidney deficiency and obstruction of turbid and stagnant blood were randomly divided into test group and control group according to the numerical table method, and the test group was given Dispelling Toxin Granules, and the control group was given Urinary Toxin Cleansing Granules, both of which were given 1 sachet each time, 3 times a day. Before and after treatment, 24h urine protein quantification, N-acyl-β-glucosaminidase (NAG), hemoglobin (Hb), plasma albumin (Serum albumin, Alb), parathyroid hormone (PTH), and other parameters were observed in the two groups. hormone (PTH), fibrinogen (Fib), serum creatinine (Scr), urea nitrogen (BUN), uric acid (UA), β2- microglobulin (β2-MG), retinol-binding protein (RBP), and other parameters. binding protein (RBP) and Chinese medicine symptom score, and calculate CCr. The observation record was made once a month for a total of 3 months. Results: After excluding invalid cases, there were 122 cases in the experimental group and 121 cases in the control group. After treatment, 24h urine protein quantification, NAG, PTH, Fib, Scr, BUN, UA, β2-MG, and RBP of patients in both groups decreased compared with the pre-treatment period (P<0.01), and Hb, Alb, and CCr increased compared with the pre-treatment period (P<0.01); comparing with the same period of the post-treatment period, the improvement of the above indexes of the test group was better than that of the control group (P<0.05). The improvement of Chinese medicine symptoms by expectorant granules was also better than that of the control group (P<0.05). The total effective rate of the experimental group was better than that of the control group (90.16% vs 66.94%), X2=24.3, P<0.01. Conclusion: Dispelling toxin granules can effectively treat chronic renal failure, and have the effects of improving renal function, reducing urinary protein, elevating plasma albumin, correcting hyperparathyroidism and coagulation, and improving clinical symptoms. Clinical study on the intervention of expectorant granules in the course of chronic renal failure Objective: To observe the intervention of expectorant granules in the course of chronic renal failure (CRF) and to explore its mechanism. Methods: CRF patients who met the diagnostic criteria of CRF were randomly divided into test group and control group according to the numerical table method, and the test group was given expectorant granules, and the control group was given urethane granules, both of which were given 1 sachet each time, 3 times a day. Observe the blood pressure, 24h urine protein quantification, plasma albumin (Serum albumin , Alb), hemoglobin (Hemoglobin , Hb), serum creatinine (Serum creatinine, Scr), urea nitrogen (BUN), uric acid (UA) of the two groups of patients were observed and recorded every 3 months, and each patient was observed for more than 12 months. The slope and regression coefficient (b) of each group were observed and compared with each other by taking blood creatinine inverse (1/SCr) as the vertical coordinate and disease duration (months) as the horizontal coordinate, and the effects of changes in blood pressure, 24-hour urine protein quantification, plasma albumin, and hemoglobin on the course of the disease were analyzed. Results: 77 cases in the experimental group and 75 cases in the control group of complete cases, the observation time of the experimental group was longer than that of the control group (42.8±18.5 months vs. 34.2±12.7 months), P<0.01; 35 cases in the experimental group did not reach the endpoint of observation at 48 months, accounting for 45.45%, and 24 cases in the control group, accounting for 32%, and the rate of not reaching the endpoint of observation of the experimental group decreased by 13.45% compared with that of the control group, P<0.01. 0.01. The regression line was plotted according to the inverse of blood creatinine (1/Scr) and time, and the b-value of the experimental group was -0.00258±0.00132, and the b-value of the control group was -0.00386±0.00167, and the slope of the experimental group was significantly smaller than that of the control group (P<0.01). After treatment, the blood pressure and 24-hour urine protein quantification of the test group were lower than that of the control group (P<0.05), and plasma albumin was higher than that of the control group (P<0.05). CONCLUSION: Expectorant granules can delay the course of CRF, and the mechanism may be related to factors such as lowering blood pressure, reducing urinary protein excretion, and elevating plasma albumin.