Please wait a minute...
Traditional Medicine Research  2018, Vol. 3 Issue (4): 173-180    DOI: 10.12032/TMR201812076
Modernization of Traditional Medicine     
Influence of astragalus polysaccharide on kidney status and fibrosis indices of a rat model of streptozotocin-induced diabetic nephropathy
Yue Ji1, Xue-Rou Yan1, Hong-Tao Yang2,*(), Kang Yang1, Qing-Yun Zhao1, Shou-Ci Hu1, Qi-Hang Su1
1 Tianjin University of Traditional Chinese Medicine, Tianjin, China.
2 The First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, China.
Download: HTML     PDF(779KB)
Export: BibTeX | EndNote (RIS)      

Highlights
Though no down-regulation effect on blood sugar was observed, astragalus polysaccharide could improve renal tubular interstitial injury in diabetic nephropathy rats and the early stage of renal function damage, which may be related to downregulation of the TGF-β1 and α-SMA.

Editor’s Summary
The application of traditional Chinese medicine in the protection and treatment of the complication of diabetic nephropathy needs further research.

Abstract
Object:To examine the effect of astragalus polysaccharide (APS) on kidney status and fibrosis indices of rats with diabetic nephropathy. Methods:72 male rats were randomly divided into three groups: negative control group (NC, n = 24); diabetic nephropathy model group (DNM, n = 24); and diabetic nephropathy model with APS group (DNM + APS, n = 24). Rats of the DNM and DNM + APS groups were subjected to both unilateral nephrectomy and administered streptozotocin (STZ) injection (65 mg/kg). DNM + APS group rats were administered 50 IU/kg/d APS by subcutaneous injection from the first week after operation until death. The NC and DNM group rats were subcutaneously injected with an identical volume of physiological saline. At weeks 3, 8, and 13 after the operation, 6 rats from each group were randomly sacrificed and blood was collected to measure serum creatinine and blood urea nitrogen. On the day before sacrifice, the rats were placed in a metabolic cage for 24 h to collect urine. At week 14 after the operation, 6 rats from each group were randomly selected to measure body weight and kidney index. Blood was collected to measure blood glucose. The kidneys were harvested to detect pathological changes by hematoxylin and eosin staining. Results:Histological assessment of DNM rats suggested damage symptoms as evidenced by hyperplasia of the glomerular mesangial matrix, atrophia of the kidney tubules, and thickening of the basement membrane. In contrast, STZ-induced diabetic nephropathy rats treated with APS (50 IU/kg/d) showed significantly improved histological results, suggesting that APS has beneficial effect on renal tissues in STZ-induced DNM rats. Our results also indicated that APS relieved renal injury and effectively improved body weight in DNM rats. The ratio of kidney weight to body weight was reduced and the early stage of renal function damage was improved after APS treatment. In the later stages of the disease, the 24 h urinary protein significantly decreased. Moreover, APS down-regulated TGF-β1 and α-SMA expression of the kidney.



Key wordsDiabetic Nephropathy      Astragalus polysaccharide      Renal index      Fibrosis      TGF-β1      α-SMA     
Published: 04 July 2018
Fund:  This work was performed at Tianjin University of Traditional Chinese Medicine, China, and was supported bya grant from the National Natural Science Fundation of China (81403218).
Corresponding Authors: Yang Hong-Tao     E-mail: dd2114@163.com
About author: They contributed equally to this work.
Cite this article:

Yue Ji, Xue-Rou Yan, Hong-Tao Yang, Kang Yang, Qing-Yun Zhao, Shou-Ci Hu, Qi-Hang Su. Influence of astragalus polysaccharide on kidney status and fibrosis indices of a rat model of streptozotocin-induced diabetic nephropathy. Traditional Medicine Research, 2018, 3(4): 173-180. doi: 10.12032/TMR201812076

URL:

https://www.tmrjournals.com/tmr/EN/10.12032/TMR201812076     OR     https://www.tmrjournals.com/tmr/EN/Y2018/V3/I4/173

Body weight (g) Kidney index (%) Blood glucose (mmol/L)
NC group 315.27 ± 51.92 0.49 ± 0.08 5.58 ± 1.05
DNM group 179.89 ± 41.03a 1.19 ± 0.18b 18.25 ± 2.89c
DNM + APS group 188.73 ± 35.66d 0.83 ± 0.16e 18.04 ± 1.12
Table 1 General statement
3w 8w 13w
NC group 6.01 ± 1.74 5.94 ± 1.87 5.64 ± 1.35
DNM group 10.39 ± 1.04a 10.81 ± 1.91b 11.10 ± 3.28c
DNM + APS group 5.89 ± 0.82d 6.96 ± 1.21e 11.03 ± 3.53
Table 2 Blood urea nitrogen changes (mmol/L)
3w 8w 13w
NC group 57.25 ± 2.45 62.43 ± 10.13 61.12 ± 9.49
DNM group 70.63 ± 5.25a 76.64 ± 6.69b 75.07 ± 12.31c
DNM + APS group 65.76 ± 6.04 64.88 ± 3.93d 71.26 ± 6.29
Table 3 Serum creatinine changes (μmol/L)
3w 8w 13w
NC group 29.50 ± 12.50 28.72 ± 9.58 30.60 ± 9.89
DNM group 43.12 ± 9.45a 34.47 ± 15.59b 56.07 ± 19.19c,d
DNM + APS group 41.55 ± 11.07 29.13 ± 13.01 31.59 ± 13.47e
Table 4 24 h proteinuria (mg/24 h)
Figure 1 HE staining
A: NC group; B: DNM group; C: DNM + APS group. NC, Negative control; DNM, Diabetic nephropathy model;DNM + APS, Diabetic nephropathy model with astragalus polysaccharide; HE, Hematoxylin and eosin.
Figure 2 Immunostaining effect of TGF-β1 and α-SMA in kidney
A: TGF-β1 expression in NC group; B: TGF-β1 expression in DMN group; C: TGF-β1 expression in DMN + APS group; D: α-SMA expression in NC group; E: α-SMA expression in DNM group; F: α-SMA expression in DNM + APS group. NC, Negative control; DNM, Diabetic nephropathy model; DNM + APS, Diabetic nephropathy model with astragalus polysaccharide; α-SMA, α-smooth muscle actin; TGF-β1, Transforming growth factor-β1.
1. Pang GM, Yan Y, Zhu P, et al. Clinic draft specification of traditional Chinese medicine about diabetic peripheral neuropathy. Chin J Tradit Chin Med Pharm 2010, 2: 260-264.
2. Wang YZ, Zhang ZH.Mechanism of diabetic Nephropathy. Chin Rem Clin 2008, 8: 58-60.
3. Xiang HD.Pathological in diabetic nephropathy. Int J Endocrinol 2004, 24: 125-136.
4. Min XL, Lan LG.Effect of Shu-Tong injection on diabetic nephropathy. Shanxi J Tradit Chin Med 2008, 29: 407-409.
5. Gao ZT, Wang G, .Effect of Huangkui capsule on micro-inflammation in diabetes patients. Chin J Integr Tradit West Nephrol 2011, 12: 1104-1105.
6. Lin L,Ni Q ,Lin XM. Tang-Wei-Kang capsule reverse diabetic nephropathy in 132 patients. J Med Res 2008, 37: 46-50.
7. Wang HW, Qing N, Pang JL, et al. Study of the Rule about Chinese Medicine in Treating Diabetic Nephropathy. Chin Arch Tradit Chin Med 2008, 26: 2365-2368.
8. Lin L, Guo L.Effect of TWK on Expression of MMP -9 in Renal Cortex in Streptozotocin - Induced Diabetic Rats. J Shanxi Coll Tradit Chin Med 2003, 4: 8-18.
9. Lin L, Qing Q, Liu XM.Effects and mechanisms of Tang-Wei-Kang capsule protecting kidney function in diabetes rat. Chin J Chin Mat Med 2003, 28: 62-66.
10. Wang W, Koka V, Lan HY.Transforming growth factor-beta and Smad signalling in kid-ney diseases. Nephrol 2005, 10: 48-56.
11. Alexopoulos E, Gionanlis L, Papayianni E, et al. Predictors of outcome in idiopathic rapi-dly progressive glomerulonephritis. BMC Nephrol 2006, 7: 1-13.
12. Wang HG.Decoction and Material Medica. People’s Medical Publishing House, 1986.
13. Wu Q.The Golden Mirror Of Medicine. Chinese Medicine Press, 2002.
14. Ji Y, Li JC, Meng JY, et al. Study of dual-directional regulatory effect of Banxia (Pinellia ternata) and Huanglian (Coptis chinensis) drug pair on gastrointestinal movement of mice. Tradit Med Res 2018, 3: 148-156.
15. Ji Y, Wang TR, Zhang KX, et al. Literature analysis of the regularity and adverse reaction of cinnamon and its prescription preparations. Chin J Pharmacovigil 2018, 15: 163-168.
16. Zhou Y, Wu Y.Effects of astragalus polysaccharide on insulin signal transduction in renal tissue of type 2 diabetic rats. J Hubei Med Univ 2005, 18: 242-247.
17. Xu Y, Zhou SW, Tang JL, et al. Optimal selection of rat models of experimental diabetic nephropathy. Acta Acad Med Milita 2006, 28: 2247-2249.
18. Li ZJ, Zhang Y.The advances in research on animal model of diabetic nephropathy. Chin B Life Sci 2011, 23: 90-95.
19. Yang F, Tang LQ, Wang FL, et al. Influential factors on the establishment of experimental diabetic nephropathy in rats. Anhui Med Pharma J 2012, 16: 735-738.
20. Yaribeygi H, Mohammadi MT, Rezaee R, et al. Fenofibrate improves renal function by amelioration of NOX-4, IL-18, and p53 expression in an experimental model of diabetic nephropathy. J Cell Biochem 2018.
21. Zhao Y, Huang W, Wang J, et al. Taxifolin attenuates diabetic nephropathy in streptozotocin-induced diabetic rats. Am J Transl Res 2018, 10: 1205-1210.
22. Boukhalfa G, Desmouliere A, Rondeau E, et al. Relationship between alpha-smooth mu-scle actin expression and fibrotic changes in human kidney. Exp Nephrol 1996, 4: 241-247.
23. Hewitson TD, Becker GJ.Interstitial myofibroblasts in IgA Glomerulonephritis. Am J Nephrol 1995, 15: 111-117.
24. Tang WW, Van GY, Qi M.Myofibroblast and alpha 1 (III) collagen in experimental tub-ulointerstitial nephritis. Kidney Int 1997, 51: 926-931.
25. Iwano M, Plieth D, Danoff TM, et al. Evidence that fibroblasts derive from epithelium d-uring tissue fibrosis. J Clin Invest 2002, 110: 341-350.
26. Grupp C, Lottermoser J, Cohen DI, et al. Transformation of rat inner medullary fibroblasts to myofibroblasts in vitro. Kidney Int 1997, 52: 1279-1290.
27. Ina K, Kitamura H, Tatsukawa S, et al. Significance of α-SMA in myofibroblasts emerge-ng in renal tubulointerstitial fibrosis. Histol Histopathol 2011, 26: 855-866.
28. Murphy JT, Duffy SL, Hybki DL,et al. Thrombin-mediated permeability of human micr-ovascular pulmo-nary endothelial cells is calcium dependent. J Trauma 2001, 50: 213-222.
29. Satpathy M, Gallagher P, Lizotte-Waniewski M, et al. Thrombin-induced phosphorylati-on of the regulatorylight chain of myosin II in cultured bovine corneal en-dothelial cells. Exp Eye Res 2004, 79: 477-486.
30. Birukova AA, Smurova K, Birukov KG, et al. Role of Rho GT pases in thrombin-induced lung vascular endothelial cells barrier dysfunction. Microvasc Res 2004, 67: 64-77.
31. Z Chen,Y Yuan,X Zou, et al. Radix Puerariae and Fructus Crataegi mixture inhibits renal injury in type 2 diabetes via decreasing of AKT/PI3K. Bmc Complementary & Alternative Medicine 2017, 17: 454-458.
32. Zhang YU,Zhou N ,Wang H,S Wang, et al. Effect of Shenkang granules on the progression of chronic renal failure in 5/6 nephrectomized rats. Experimental & Therapeutic Medicine 2015, 9: 2034-2042.
33 33.Y Lian, L Xie, M Chen, et al. Effects of an astragalus polysaccharide, and rhein combination on apoptosis in rats with chronic renal failure[J]. Evid Based Complement Alternat Med 2014, 27:1862-1868.
34. Lai YN, Yu MH, Zhu QY, et al. Effect of astragalus polysoccharidde on TGF-β1 in renal tissue of diabetic rats. Fudan Univ J Med Sci 2002, 29: 255-257.
35. Li ZJ, Zhang Y, Liu YM, et al. Effect of astragalus polysaccharin on expression of nephrin and podocin in podocytes of early diabetic nephropathy rats. Chin J Pathophysiol 2011, 27: 1772-1776.
[1] Rui Tang, Qia-Qia Li, Di Wang, Jing Chen, Jin-Hua Huang, Qing-Hai Zeng. The protective effect of Dendrobium officinale polysaccharides on photoaging fibroblasts by scavenging reactive oxygen species and promoting the expression of TGF-β1[J]. Traditional Medicine Research, 2018, 3(3): 131-139.
[2] Nie Hai-Yang, Chen Rui, Zhang Hong-Na, Pan Zhi. Effects of saponin from the seed of Litchi chinensis Sonn on TGF-β1, FN and SOCS-1 in renal tubular epithelial cells under high glucose[J]. Traditional Medicine Research, 2017, 2(3): 144-148.