Potential mechanism of Danggui Shaoyao Powder on renal protection in db/db mice based on transcriptomics
Objective To explore the renal protective mechanism of Danggui Shaoyao Powder(DGSYP)on diabetic nephropathy in db/db mice through transcriptomics and experimental verification.Methods A total of 25 eight-week-old db/db mice were randomized into model group(20 mL/kg distilled water),dapagliflozin group(1.3 mg/kg),low-dose DGSYP group(8.39 g/kg),medium-dose DGSYP group(16.77 g/kg),and high-dose DGSYP group(33.54 g/kg),with five mice in each group.Another five db/m mice of the same age were set as blank group(20 mL/kg distilled water),and each group was intragastrically administered once a day for six consecutive weeks.After administration,the body weight,fasting blood glucose(FBG),and area under the curve(AUC)of the oral glucose tolerance test(OGTT)were measured.Urine albumin creatinine ratio(UACR),triglyceride(TG),and total cholesterol(TC)were determined by automatic biochemical analyzer.Serum creatinine(Scr)was examined by creatinine colorimetry.The blood urea nitrogen(BUN)was checked by urea colorimetry.HE staining was used to observe the pathological morphology of renal tissue.The differential genes in mouse renal tissue were determined by transcriptome chip technology,and the differential genes of mice in DGSYP group were analyzed by KEGG enrichment analysis.The mRNA expression levels of core genes with TPM＞10 in renal tissue were determined by RT-PCR.Results Compared with the blank group,the model group showed significant increases in body weight,OGTT-AUC,FBG,UACR,Scr,BUN,TG,and TC(P＜0.01).Compared with the model group,the dapagliflozin group and DGSYP groups showed decreases in body weight,OGTT-AUC,FBG,UACR,Scr,BUN,TG,and TC(P＜0.05,P＜0.01).Compared with the blank group,a total of 1 129 differential genes were screened out in the model group,including 337 up-regulated differential genes and 792 down-regulated differential genes.Compared with the model group,a total of 271 differential genes were screened out in medium-dose DGSYP group,including 195 up-regulated differential genes and 76 down-regulated differential genes.There were 57 differentially expressed genes in the blank group,model group,and the medium-dose DGSYP group,among which there were 12 core genes with TPM＞10,including Gsta2,Cyp4a12a,Slc8a1,Abcc4,Cpeb4,Serpina1b,Npl,Aacs,Kap,Slc5a10,Tmem252,and Ifi27l2a.The mRNA expression levels of the 12 core genes were consistent with the transcriptome sequencing trend.Compared with the model group,the mRNA expression levels of Gsta2,Abcc4,Slc8a1,and NPL in the medium-dose DGSYP group increased(P＜0.05,P＜0.01),while the mRNA expression levels of Slc5a10 and Tmem252 decreased(P＜0.05).The differential genes in the medium-dose DGSYP group were enriched in drug metabolism-cytochrome P450,glutathione metabolism,and reactive oxygen species,and other related pathways.Conclusion DGSYP can improve the prognosis of diabetic nephropathy,and its mechanism may be related to regulating Gsta2,Slc5a10,Abcc4,Slc8a1,Tmem252,Npl,and other gene expressions as well as modulating cytochrome P450,glutathione metabolism,reactive oxygen species,and other signaling pathways.
万方数据
维普
