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Comparative Study
. 2020 Dec;58(1):1123-1130.
doi: 10.1080/13880209.2020.1844242.

Effects of HuoxueJiangtang decoction alone or in combination with metformin on renal function and renal cortical mRNA expression in diabetic nephropathy rats

Xuemei Liu  1 , Deliang Liu  1 , Youyou Shuai  1 , Huilin Li  1 , Hengxia Zhao  1 , Xin Qu  1 , Shufang Chu  1 , Xuewen Zhang  2
Affiliations
Comparative Study

Effects of HuoxueJiangtang decoction alone or in combination with metformin on renal function and renal cortical mRNA expression in diabetic nephropathy rats

Xuemei Liu et al. Pharm Biol. 2020 Dec.

Abstract

Context: HuoxueJiangtang decoction (ZY) is a traditional Chinese medicine for the treatment of diabetes.

Objective: The protective effect of ZY on renal injury in diabetic nephropathy rats was investigated in this study.

Materials and methods: Fifty 4-week-old SPF Wistar male rats were selected to construct diabetic nephropathy model rats (DN) group by continuous high-fat feeding for 4 weeks, followed by a tail vein injection of 30 mg/kg streptozotocin for 1 week. The experimental rats were divided into six groups of 10 rats: normal (control), DN, DN + ZY, DN + metformin, DN + metformin + ZY, and DN + metformin + captopril (positive control) groups. Among the groups, 6.25 g/kg ZY, 250 mg/kg metformin, and 17.5 mg/kg captopril were given to the rats by gavage once a day for 16 weeks. Blood glucose, dietary behaviour, biochemical indicators, and gene expression changes were measured in each group.

Results: Metformin + ZY treatment significantly lowered blood glucose, water intake, urine total protein, urine albumin, urine volume, serum triglyceride, and serum cholesterol levels in the DN group. The pathological changes of kidney tissue showed that the DN + metformin + ZY group had a protective effect on kidney tissue damage. And ZY and metformin + ZY treatments repaired the expression of genes in the DN group.

Discussion and conclusion: The ZY and metformin combined treatment showed a clear therapeutic effect on kidney damage in DN. This study provides a potential mechanism for the treatment of diabetic nephropathy with ZY combined with metformin.

Keywords: Blood glucose; biochemical indicator; kidney; pathological change.

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Conflict of interest statement

No potential conflict of interest was reported by the author(s).

Figures

Figure 1.
Figure 1.
OGTT showed blood glucose levels in diabetic model rats and normal rats (control). OGTT: oral glucose tolerance test; *p < 0.05 vs. control.
Figure 2.
Figure 2.
Effects of ZY on blood glucose, food intake, water intake, and biochemical parameters of DN. (A) Blood glucose, (B) food intake, (C) water intake, (D) 24 h urine total protein, (E) urine albumin, (F) urine volume, (G) serum triglyceride, (H) serum cholesterol, (I) serum HDL-CH, (J) serum LDL-CH, (K) serum urea, and (L) serum creatinine levels in the normal rats (control) and in DN with different treatments. ZY: HuoxueJiangtang decoction; DN: diabetic nephropathy model rat; HDL-CH: high-density lipoprotein-CHOL; LDL-CH: low-density lipoprotein-CHOL; DN + ZY: DN treated with ZY; DN + metformin: DN treated with metformin; DN + metformin + ZY: DN treated with metformin combined with ZY; DN + metformin + captopril: DN treated with metformin combined with captopril. *p < 0.05 vs. control; #p < 0.05 vs. DN.
Figure 3.
Figure 3.
Histopathological analysis showed changes in the renal cortex in response to different drug treatments. (A) H&E staining, PAS staining, and Masson’s trichrome staining showed changes in the normal rats (control) and model rats with different drug treatments. (B) Transmission electron microscopy showed the effects of different drug treatments on the glomerular ultrastructure. GBMs were quantified based on these representative images. H&E: haematoxylin and eosin; PAS: Periodic Acid–Schiff; GBMs: glomerular basement membranes; ZY: HuoxueJiangtang decoction; DN: diabetic nephropathy model rat; control + ZY: normal rats treated with ZY; DN + ZY: DN treated with ZY; DN + metformin: DN treated with metformin; DN + metformin + ZY: DN treated with metformin combined with ZY; DN + metformin + captopril: DN treated with metformin combined with captopril. Bars represent 10 and 20 μm. *p < 0.05 vs. control; **p < 0.01 vs. control; #p < 0.05 vs. DN.
Figure 4.
Figure 4.
RNA sequencing indicated differentially expressed genes in DN and DN treated with different drugs. (A) The heatmap showed the differentially expressed genes. (B) The Venn diagram showed commonly and specifically expressed genes in each group of rats. (C) KEGG enrichment analysis showed the top 20 most differentially expressed genes in the control group compared with the DN group. (D) KEGG enrichment analysis showed the top 20 most differentially expressed genes in the DN + metformin group compared with the DN + metformin + ZY group. ZY: HuoxueJiangtang decoction; DN: diabetic nephropathy model rat; KEGG: Kyoto Encyclopaedia of Genes and Genomes; DN + ZY: DN treated with ZY; DN + metformin: DN treated with metformin; DN + metformin + ZY: DN treated with metformin combined with ZY; DN + metformin + captopril: DN treated with metformin combined with captopril.
Figure 5.
Figure 5.
The heatmap generated with RNA sequencing data showed the differentially expressed genes in DN treated with different drugs. ZY: HuoxueJiangtang decoction; DN: diabetic nephropathy model rat; DN + ZY: DN treated with ZY; DN + metformin + ZY: DN treated with metformin combined with ZY.
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References

    1. Alhaider AA, Korashy HM, Sayed-Ahmed MM, Mobark M, Kfoury H, Mansour MA.. 2011. Metformin attenuates streptozotocin-induced diabetic nephropathy in rats through modulation of oxidative stress genes expression. Chem Biol Interact. 192(3):233–242. - PubMed
    1. Alpers CE, Hudkins KL.. 2018. Pathology identifies glomerular treatment targets in diabetic nephropathy. Kidney Res Clin Pract. 37(2):106–111. - PMC - PubMed
    1. American Diabetes Association. 2014. Diagnosis and classification of diabetes mellitus. Diabetes Care. 37(Suppl 1):S81–S90. - PubMed
    1. Arcaro CA, Assis RP, Zanon NM, Paula-Gomes S, Navegantes LCC, Kettelhut IC, Brunetti IL, Baviera AM.. 2018. Involvement of cAMP/EPAC/Akt signaling in the antiproteolytic effects of pentoxifylline on skeletal muscles of diabetic rats. J Appl Physiol. 124(3):704–716. - PubMed
    1. Basta-Jovanovic G, Venkataseshan VS, Gil J, Kim DU, Dikman SH, Churg J.. 1990. Morphometric analysis of glomerular basement membranes (GBM) in thin basement membrane disease (TBMD). Clin Nephrol. 33(3):110–114. - PubMed

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