| ObjectivesThe purpose of this study was to observe the effects of Huoxue Jiangtang Decoction on glucose and lipid metabolism,creatinine,24-hour urinary albumin excretion rate and neutrophil gelatinase-associated lipocalin in patients with diabetic nephropathy,and to establish a rat model of diabetic nephropathy,to observe the general biochemical indicators and pathological changes of kidney tissue in rats after the intervention of Huoxue Jiangtang Decoction,and to analyze the bioinformatics of kidney tissue.To explore the molecular mechanism of Huoxue Jiangtang Decoction in treating diabetic nephropathy.Methods1.Clinical research part60 cases with early diabetic nephropathy of deficiency of both Qi and Yin with blood stasis syndrome were randomly divided into control group and treatment group from October 2017 to October 2018.Each group of 30 case.The control group was treated with Perindopril indapamide tablets,while the treatment group was treated with Huoxue Jiangtang Yin on the basis of the control group for 8 weeks.Glycated hemoglobin(HbAlc),fasting blood glucose(FPG),triglyceride(TG),total cholesterol(TC),high density lipoprotein cholesterol(HDL-C),low density lipoprotein cholesterol(LDL-C),creatinine(Scr),serum cystatin C(Cys-C),24-hour urinary albumin excretion rate(UAER),neutrophil gelatinase-associated lipocalin(NGAL)and TCM symptom scores were observed before and after treatment.2.Experimental research partWistar rats were fed with high fat diet and injected with streptozotocin(STZ)into tail vein to establish diabetic model.The rats were divided into model group(DN),Metformin+traditional Chinese medicine group(DN+Met+ZY)and Metformin+captopril group(DN+Met+Cap).The rats in each group were given corresponding drugs by gavage,and another normal control group(Control)was set up.After 16 weeks of intervention,the fasting blood glucose(FPG),blood lipid(TC,TG,HDL-C,LDL-C),Nitrogen(BUN),creatinine(Scr),24-hour urinary protein(24h UTP)and urine microalbumin(24h mALB)were observed in each group.At the same time,pathological changes of kidney tissue were observed by electron microscopy,HE staining,PAS staining and Masson staining.RNA-seq was sequenced in kidney tissues of rats in normal group,model group and biguanide plus traditional Chinese medicine group.Results1.Clinical research partBaseline characteristics were well balanced between the two groups before treatment(P>0.05);After treatment,HbAlc,FPG,TG,TC,LDL-C,Scr,Cys-C,UAER,NGAL and TCM symptoms scores of the two groups decreased significantly(P<0.05),and the treatment group was better than the control group(P<0.05);after treatment,the HDL-C of the two groups did not change significantly(P>0.05).There were no adverse reactions during the treatment.2.Experimental research part(1)General biochemical indicators:Compared with the normal group,FPG,TC,TG,LDL-C,Scr,BUN,24h UTP,24h mALB in the model group increased significantly(P<0.01),while HDL-C decreased significantly(P<0.01);after treatment,FPG,TC,TG,LDL-C,Scr,BUN,24h UTP,24h mALB decreased significantly(P<0.01?P<0.05),but HDL-C did not.Compared with the Met+Cap,FPG,TC,TG and LDL-C in the group of Met+ZY were significantly lower(P<0.01,P<0.05).There were no significant differences in HDL-c,Scr,BUN,24h UTP and 24h mALB between the two groups(P>0.05).(2)HE staining,Masson staining,PAS staining and electron microscopy showed that compared with the normal group,the pathological changes of kidneys in the model group were obvious;compared with the model group,the pathological changes of kidneys in the two groups(DN+Met+ZY?DN+Met+Cap)were significantly improved.(3)The results of transcriptome sequencing showed that the total number of genes in DNvs.Control and DN+Met+ZYvs.DN transcripts was close,and 10 bidirectional regulatory genes with the most obvious difference in expression were screened out;GO enrichment analysis showed that the differentially expressed genes in DNvs.Control and DN+Met+ZYvs.DN were mainly annotated to the biological process category;analysis of the first 20 significant enrichment pathways in KEGG showed that there were metabolic related pathways and cAMP signal pathways in the interaction of DNvs.Control and DN+Met+ZYvs.DN.ConclusionsHuoxue Jiangtang Decoction in the treatment of diabetic nephropathy can effectively correct the disorder of glycolipid metabolism,reduce the excretion of urinary albumin,improve renal function,and improve the pathological changes of kidney in diabetic nephropathy,alleviate the progress of diabetic nephropathy.It may be mediated by multiple targets such as Cftr,Pdk4,Angptl4 and Hmgcs2. |
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