The Clinical Effcct Of YIQI YANGYIN HUOXUE Recipe In The Treatment Of Early Diabetic Nephropathy And Related Mechanism Research

ObjectiveBased on the guiding principles of TCM macroscopic syndrome differentiation and Western medicine micro diagnosis and examination,combined with TCM theory and Western medicine practice,summarize the understanding of TCM and Western medicine on early diabetic nephropathy,and combine clinical trials and animal experiments to explore the effect of Yiqi Yangyin Huoxue Fang on early diabetic nephropathy(Diabetic kidney disease,DKD)therapeutic effect.In terms of clinical research,observe the TCM syndrome scores(total scores of TCM syndromes and single main symptom scores of TCM syndromes),glucose and lipid metabolism,for patients with early diabetic nephropathy with deficiency of both qi and yin and collateral stasis syndrome.Blood pressure,urine microalbumin to urine creatinine ratio(UACR),blood creatinine(SCr),urea nitrogen(BUN),cystatin-C(Cys-C),glomerular filtration rate(GFR),interleukin-6(IL-6),tumor necrosis factor-α(TNF-α).In animal experiments,observe the effects of Yiqi Yangyin Huoxue Recipe on blood glucose,urine microalbumin,kidney tissue pathological changes and TRPC6,RhoA protein,transcription factor P300,silencing regulator SIRT1,miR-222 in early diabetic nephropathy rat models Influence of expression level.This study explores the clinical efficacy and mechanism of Yiqi Yangyin Huoxue Decoction in the treatment of early diabetic nephropathy,in order to find new ways of treating diabetic nephropathy with Chinese medicine,and in order to improve the clinical application value of this method in the treatment of early diabetic nephropathy.Method1.Clinical Research Randomly select 100 patients with early diabetic nephropathy with Qi-yin deficiency and collateral stasis syndrome that meet the diagnostic criteria.A randomized,controlled method was adopted.After the introduction period,they were enrolled into the group and divided into a traditional Chinese medicine treatment group and western medicine group as control with 50 cases each.The traditional Chinese medicine treatment group was treated with Yiqi Yangyin Huoxue Decoction,and the western medicine control group was treated with Western medicine valsartan.Both groups underwent a 12-week treatment observation.The main observation indicators are as follows:1)General observation indicators:age,gender,body mass index(BMI),disease course,blood pressure,etc.2)Curative effect observation index:TCM syndrome integra1.3)Glucose metabolism indicators including ①fasting blood glucose(FBG),②postprandial blood glucose(PBG)and ③glycated hemoglobin(HbA1C).4)Lipid metabolism indicators:serum total cholesterol(TC),triglycerides(TG),low-density lipoprotein cholesterol(LDL-C).5)Renal function indicators:UACR,SCr,BUN,Cys-C,GFR.6)Inflammatory cytokines:IL-6,TNF-α.7)Safety observation indicators:① incidence of hypoglycemia;②incidence of adverse reactions;③liver and kidney function indicators including alanine aminotransferase(ALT),aspartate aminotransferase(AST),creatinine(Scr).2.Animal experiments Ninety male SD rats that have completed adaptive feeding were randomly selected as healthy control group,80 of which were fed with high-fat and high-sugar diet for 6 weeks,and combined with low-dose streptozotocin(STZ)to destroy Pancreatic islet cells form a rat model of early diabetic nephropathy as the disease progresses.80 modules were made,and 6 of them were unsuccessful.The 74 SD rats that were successfully modeled were randomly divided into diabetes model group(STZ group),western medicine group as control(valsartan),low-dose group of Yiqi Yangyin Huoxue Decoction,and Yiqi Yangyin Huoxue Decoction.The middle-dose group and the 5 groups of the high-dose group of Yiqi Yangyin Huoxue Decoction included 14 in the western medicine control group and 15 in each group.Intragastric treatment according to the corresponding drug dosage for 12 weeks,monitoring the clinical manifestations and body changes of the rat models in each group,collecting blood from the tail vein to monitor the blood glucose level,enzyme-linked immunoassay kit one-step method to determine the urine microalbumin,HE staining optical microscope to examine the kidney tissue Pathological changes,Western Blot detected TRPC6,RhoA protein,transcription factor P300,silencing factor SIRT1,miR-222 expression levels.Result1.Clinical Research The main observation indexes of the treatment group and the control group were statistically analyzed,and the results were summarized as follows:1)There was no significant difference in age,gender,body mass index(BMI),course of disease,blood pressure,etc.between the two groups before treatment(P>0.05).But after treatment,the systolic and diastolic blood pressure of the two groups were improved much better when compared with before treatment.There is a statistical difference(P<0.05);comparing SBP and DBP between groups,the treatment group is better than the control group,and there is a statistical difference(P<0.05).2)TCM syndrome scores,both groups have a significant decrease compared with before treatment(P<0.05);comparison between the two groups has a significant decrease in the TCM treatment group than the western medicine control group(P<0.05),indicating its The difference is significant.3)Glucose metabolism indicators:FBG,PBG,HbA1C,both groups were lower than before treatment,with statistical differences(P<0.05);comparison between groups,the treatment group was better than the control group,with statistical differences(P<0.05).Compared with blood glucose curative effect,the effective rate of the treatment group was higher than that of the control group,with statistical difference(P<0.05).4)Lipid metabolism indexes:TC,TG and LDL-C decreased compared with before treatment,with statistical difference(P<0.05);comparison between groups,TC,LDL-C,LDL-C,the treatment group was better than the control Group,there is statistical difference(P<0.05).5)Renal function indicators:UACR,SCr,BUN,Cys-C,and GFR were all lower than before treatment,with statistical differences(P<0.05);comparison between groups,the treatment group was better than the control group,with statistical differences(P<0.05).6)Inflammatory cytokines:IL-6 and TNF-α both decreased compared with before treatment,with statistical difference(P<0.05);comparison between groups,the treatment group was better than the control group,with statistical difference(P<0.05)).7)Safety observation indicators:There was no hypoglycemia during the treatment of the two groups of patients,2 cases of mild adverse reactions occurred in the treatment group,accounting for 4.10%,the control group had no obvious adverse reactions,and there was no statistical difference between the groups(P>0.05).2.Animal experiments 1)Blood glucose level.Before therapy,the blood glucose of the remaining groups were significantly increased compared with the healthy control group,with significant statistical difference(P<0.05).After therapy,the blood glucose of the model group increased;the blood glucose levels of the western medicine control group and the low,medium and high dose groups of Yiqi Yangyin Huoxue Recipe decreased compared with before treatment,and the difference was statistically significant(P<0.05);Compared between groups,the blood glucose levels of rats in the western medicine control group and the low,medium and high dose groups of Yiqi Yangyin Huoxue Recipe were significantly decreased than those of the model group,and the difference was statistically significant(P<0.05).The improvement of blood glucose in the middle and high-dose groups of Yiqi Yangyin Huoxue Recipe was significantly better than that of the low-dose Yiqi Yangyin Huoxue Recipe group and the western medicine control group,the difference was statistically significant(P<0.05).2)The level of glycosylated hemoglobin(HbA1c)in healthy control group and model group was basically unchanged.The level of glycosylated hemoglobin in diabetic rats with early nephropathy model was lower than that before treatment.The western medicine control group remained stable after decreasing.The glycosylated hemoglobin level of diabetic rats with early nephropathy treated by Yiqi Yangyin Huoxue Decoction increased with time,and the better the improvement of glycosylated hemoglobin was.After 12 weeks of treatment,the level of glycosylated hemoglobin was basically consistent with that of healthy rats.However,the improvement of glycosylated hemoglobin level of middle and high dose Yiqi Yangyin Huoxue decoction was significantly better than that of Western medicine control group and low-dose Yiqi Yangyin Huoxue Decoction group(P<0.05).3)Urinary microalbumin levels,except for the healthy control group and the diabetes model group,the urine microalbumin levels of the early diabetic nephropathy rat models in each group decreased compared with before treatment,the difference was statistically significant(P<0.05).The middle and high-dose groups of Yiqi Yangyin Huoxue Decoction improved the level of urinary microprotein significantly higher than the western medicine control group and the low-dose Yiqi Yangyin Huoxue Decoction group,the difference was statistically significant(P<0.05).4)The pathological changes of kidney tissues.Observed by HE staining and optical microscope,except for the healthy control group,the kidney cells of the other groups have different degrees of pathological changes.After treatment,the degree of renal cell pathological changes in each administration group has different degrees improve.The kidney cell pathological changes of the middle and high dose groups of Yiqi Yangyin Huoxue Recipe were significantly relieved,which was close to that of the healthy control group.5)The expression levels of TRPC6 and RhoA in the middle and high dose groups of Yiqi Yangyin Huoxue Prescription were significantly decreased,with statistical significance(P<0.05).6)Yiqi Yangyin Huoxue Decoction down-regulated the level of transcription factor P300 and up-regulated the level of silence regulator SIRT1.7)The expression level of miR-222 in early diabetic nephropathy model of diabetic rats in three dosage groups of Yiqi Yangyin Huoxue recipe was significantly decreased compared with those in the western medicine group(P<0.05).Conclusion1.Yiqi Yangyin Huoxue Decoction can effectively reduce the scores of TCM syndromes of patients with deficiency of both Qi and Yin and stagnation of collaterals in early diabetic nephropathy,and improve the clinical symptoms of TCM.2.Yiqi Yangyin Huoxue Decoction can regulate the metabolism of sugar and lipid,reduce the excretion rate of urinary protein,protect the normal renal physiological function of patients,and delay the development of their disease3.Yiqi Yangyin Huoxue Decoction can reduce the blood sugar level,HbA1c,TRPC6,RhoA protein expression level in diabetic early nephropathy rats.4.Yiqi Yangyin Huoxue Decoction can down-regulate the expression of transcription factor P300,up-regulate the expression of silence regulator SIRT1,delay glomerulosclerosis and delay the development of patients’ condition.5.Yiqi Yangyin Huoxue Decoction can down-regulate the expression of microRNA-222 and inhibit the apoptosis of kidney cells.