| Objective: To evaluate the clinical efficacy of Shen’an Tongluo Decoction based on "toxin impairing kidney collateral" in the treatment of diabetes kidney disease(deficiency of both spleen and kidney,syndrome of blood stasis and toxin blocking collateral),preliminarily explore its mechanism of kidney protection,enrich the scientific connotation of the theory of "toxin impairing kidney collateral",and provide new ideas for the treatment of clinical diabetes kidney disease.Methods: 1.Clinical study: 72 cases of diabetes kidney disease(spleen and kidney deficiency,blood stasis and toxin blocking collateral syndrome)were randomly divided into treatment group and control group with 36 cases each.The treatment group was treated with basic treatment combined with Shen’an Tongluo Decoction;The control group was treated with basic treatment combined with oral valsartan capsules.After 12 weeks of continuous treatment,observe the clinical efficacy,TCM symptom scores,renal function,blood glucose,blood lipids,and changes in serum levels of HIF-a,VEGF,KDR,Ang-1,and Tie2 in the two groups.2.Animal experiment: Sixty SD rats were divided into a blank group(8 rats)and a model group(52 rats).The model group was established by unilateral nephrectomy combined with low dose STZ injection,and fed with high fat and high sugar diet.After successful modeling,the model group was again divided into five groups: model group,control group,high,medium,and low dose groups of traditional Chinese medicine.The traditional Chinese medicine group was given high,medium,and low dose Shen’an Tongluo Decoction by gavage,and the control group was given valsartan solution by gavage,The model group and the blank group were given distilled water by gavage.After 8 weeks of continuous administration,blood creatinine,urinary protein,blood glucose,and other related indicators were detected,and the pathological morphology of the rat kidneys was observed.3.Metabolomics study: Rats in each experimental group took blood on an empty stomach in the early morning of the 12 th week,and took serum for 1HNMR metabolomics testing.The original nuclear magnetic data were processed using the software Mest Re Nova-12.0.3-21384;Differential Metabolites and Metabolic Pathways Analysis The metaba Analyst 4.0database was used to analyze the differential metabolites and metabolic pathways in each group after treatment using online metabolic data analysis tools.Results:1.Clinical research results: The total effective rate of Shen’an Tongluo Decoction in the treatment of diabetes kidney disease(syndrome of spleen and kidney deficiency,blood stasis and toxin blocking collaterals)is 84.99%,and the effective rate of the control group is 66.70%;After 12 weeks of treatment,the renal function and clinical symptoms of the two groups of patients were improved,and the treatment group was superior to the control group in improving clinical symptoms,reducing urinary protein,lowering blood sugar,and lowering blood lipids.However,there was no significant difference between the treatment group and the control group in reducing serum creatinine,and improving glomerular filtration rate.After treatment,the serum levels of HIF-a,VEGF,KDR,and Tie2 in the patients decreased,and the treatment group was superior to the control group.2.Animal experiment results: After modeling,the amount of drinking water,food intake,and urine of the rats increased,and their weight decreased.After 8 weeks of intervention in each group,the amount of drinking water,food intake,and urine decreased,and the weight loss of the rats was slower than that of the model group.Among them,the high and middle dose groups of traditional Chinese medicine were superior to the control group and the low dose group of traditional Chinese medicine;At the same time,compared with the model group,after intervention,each group showed varying degrees of regulatory effects on blood glucose,serum creatinine,and 24-hour urinary protein levels,with high and medium dose groups having better regulatory effects on blood glucose than the control group.HE staining of renal tissue showed that in the model group,the glomerulus increased and hardened,mesangial cells and stroma proliferated,and renal tubular epithelial cells showed vacuolar appearance.After drug intervention,the renal pathological morphology of rats in each group showed different degrees of improvement.3.The results of metabonomics analysis showed that there were 31 different metabolites between the model group and the blank group,mainly involving glucose and lipid metabolism disorders,amino acid metabolism disorders,and energy metabolism disorders.The high dose group of Shen’an Tongluo Decoction corrected the abnormal expression of24 metabolites,the medium dose group was able to correct the expression of 18 differential metabolites,and the low dose group corrected the expression of 15 metabolites,Analysis showed that there were 7 metabolic pathways with an impact factor greater than 0.1,and there were 3 metabolic pathways in each group of traditional Chinese medicine,including alanine and aspartic acid metabolic pathways,D-glutamine and D-glutamic acid metabolic pathways,and arginine and proline metabolic pathways.Conclusion: 1.Clinical research shows that Shen’an Tongluo Decoction based on "toxin impairing the kidney collateral" has a definite effect on diabetes kidney disease(syndrome of deficiency of both spleen and kidney,blood stasis and toxin blocking the collateral),can reduce blood creatinine,reduce proteinuria,improve renal function,improve patients’ clinical symptoms,and has a certain hypoglycemic and lipid-lowering effect.It can improve the hypoxia environment of the body and inhibit the formation of new blood vessels by regulating the expression of HIF-a,VEGF,KDR,Ang-1,and Tie2,Play a protective role in the kidneys.2.The results of animal experiments show that Shen’an Tongluo Decoction can improve the renal function of rats,reduce blood creatinine,urinary protein,slow down the rate of weight loss of rats,reduce the amount of water,food and urine of rats,have a positive effect on regulating blood sugar of rats,and can reduce the degree of renal damage of diabetes nephropathy to a certain extent,and delay the course of disease.3.Metabonomic studies have shown that Shen’an Tongluo Decoction can correct the disorder of glucose and lipid metabolism,amino acid metabolism,and energy metabolism caused by DKD,thereby protecting the kidney and delaying the course of disease.Its mechanism of action may be achieved by regulating major metabolic pathways such as alanine and aspartic acid metabolic pathways,D-glutamine and D-glutamic acid metabolic pathways,arginine and proline metabolism Among them,D-glutamine and D-glutamate metabolic pathways are of great significance for the treatment of DKD. |
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