Journal of Traditional Chinese Medicine ›› 2022, Vol. 42 ›› Issue (5): 723-731.DOI: 10.19852/j.cnki.jtcm.2022.05.006
• Research Articles • Previous Articles Next Articles
ZHAO Jie1,3, WANG Li3, CAO Ai-li3, WANG Yun-man2, CHI Yang-feng2, WANG Yi2, WANG Hao2,3(), PENG Wen2,3()
Received:
2021-07-12
Accepted:
2021-10-14
Online:
2022-10-15
Published:
2022-09-02
Contact:
WANG Hao,PENG Wen
About author:
Prof. WANG Hao, Department of Nephrology, Laboratory of Renal Disease, Putuo Hospital, Shanghai University of Chinese Medicine, Shanghai 200062, China. wang402hao@163.comSupported by:
ZHAO Jie, WANG Li, CAO Ai-li, WANG Yun-man, CHI Yang-feng, WANG Yi, WANG Hao, PENG Wen. Huangqi decoction (黄芪汤) attenuates renal interstitial fibrosis via transforming growth factor-β1/mitogen-activated protein kinase signaling pathways in 5/6 nephrectomy mice[J]. Journal of Traditional Chinese Medicine, 2022, 42(5): 723-731.
Group | Week 1 | Week 4 | Week 8 | Week 12 | Week 16 |
---|---|---|---|---|---|
Sh | 116.9±6.4 | 119.8±6.8 | 125.8±7.6 | 125.3±7.1 | 125.7±2.5 |
Nx | 112.8±7.0 | 129.9±7.5 | 150.5±2.3a | 151.9±6.5a | 155.0±4.8a |
En | 110.4±6.4 | 121.4±6.5 | 130.0±5.2b | 121.8±4.0b | 122.9±3.9c |
Hl | 114.0±5.3 | 139.9±8.9 | 140.8±6.4 | 141.5±7.4 | 147.9±7.1 |
Hm | 118.3±6.6 | 136.0±10.0 | 143.4±7.9 | 142.6±5.5 | 147.7±3.3 |
Hh | 115.8±6.8 | 128.3±9.3 | 138.9±10.1 | 142.0±7.2 | 145.3±8.6 |
Table 1 Effect of Huangqi decotion on the blood pressure of the mice (mean, n = 6)
Group | Week 1 | Week 4 | Week 8 | Week 12 | Week 16 |
---|---|---|---|---|---|
Sh | 116.9±6.4 | 119.8±6.8 | 125.8±7.6 | 125.3±7.1 | 125.7±2.5 |
Nx | 112.8±7.0 | 129.9±7.5 | 150.5±2.3a | 151.9±6.5a | 155.0±4.8a |
En | 110.4±6.4 | 121.4±6.5 | 130.0±5.2b | 121.8±4.0b | 122.9±3.9c |
Hl | 114.0±5.3 | 139.9±8.9 | 140.8±6.4 | 141.5±7.4 | 147.9±7.1 |
Hm | 118.3±6.6 | 136.0±10.0 | 143.4±7.9 | 142.6±5.5 | 147.7±3.3 |
Hh | 115.8±6.8 | 128.3±9.3 | 138.9±10.1 | 142.0±7.2 | 145.3±8.6 |
Figure 1 Effect of Huangqi decotion on weight,kidney index and blood pressure changes. A: the body weight during the first week; B: the body weight at the end of week17; C: the body weight during the whole process; D: the weight of the remanent kidney; E: the kidney index of the mice. Sh group was the control group; Nx group was the 5/6 nephrectomy model group; En group was the control group by Enalapri; Hl group was the Low dosing of Huangqi decotion group (Hl, 0.12g /kg, n = 20); Hm group was the Medium dosing of Huangqi decotion group (Hm, 0.36g/kg, n = 20); HH group was the High dosing of Huangqi decotion group (HH, 1.08g/kg, n = 20). Sh: Sham group; En: Enalapri group; Nx: 5/6 nephrectomy model group; Hh: High dosing of Huangqi decotion group; Hm: Medium dosing of Huangqi decotion group; Hl: Low dosing of Huangqi decotion group. aP < 0.05, compared with Sham group; bP < 0.01 or cP < 0.05, compared with Nx group, n = 8-11.
Group | Week 1 | Week 4 | Week 8 | Week 12 | Week 16 |
---|---|---|---|---|---|
Sh | 4.0±0.4 | 3.8±0.4 | 3.5±0.2 | 3.4±0.3 | 3.9±0.3 |
Nx | 4.0±0.4 | 1.3±0.2a | 1.3±0.2a | 16.9±0.7a | 16.8±0.6a |
En | 3.9±0.3 | 1.9±0.3 | 1.4±0.1 | 10.6±0.6b | 9.4±0.2c |
Hl | 4.0±0.4 | 1.0±0.2 | 1.4±0.2 | 17.2±0.7 | 16.4±0.6 |
Hm | 3.9±0.3 | 1.0±0.1 | 2.5±0.2b | 16.4±0.6 | 15.8±0.5 |
Hh | 3.9±0.2 | 1.6±0.2 | 2.8±0.2c | 16.8±0.5 | 13.8±0.5b |
Table 2 Effect of Huangqi decotion on 24 h urinary protein (s, n = 6)
Group | Week 1 | Week 4 | Week 8 | Week 12 | Week 16 |
---|---|---|---|---|---|
Sh | 4.0±0.4 | 3.8±0.4 | 3.5±0.2 | 3.4±0.3 | 3.9±0.3 |
Nx | 4.0±0.4 | 1.3±0.2a | 1.3±0.2a | 16.9±0.7a | 16.8±0.6a |
En | 3.9±0.3 | 1.9±0.3 | 1.4±0.1 | 10.6±0.6b | 9.4±0.2c |
Hl | 4.0±0.4 | 1.0±0.2 | 1.4±0.2 | 17.2±0.7 | 16.4±0.6 |
Hm | 3.9±0.3 | 1.0±0.1 | 2.5±0.2b | 16.4±0.6 | 15.8±0.5 |
Hh | 3.9±0.2 | 1.6±0.2 | 2.8±0.2c | 16.8±0.5 | 13.8±0.5b |
Figure 2 Effect of Huangqi decotion on renal function. A: effect of Huangqi decotion on serum creatinine; B: effect of Huangqi decotion on blood urea nitrogen. Sh group was the control group; Nx group was the 5/6 nephrectomy model group; En group was the control group by Enalapri; Hl group was the Low dosing of Huangqi decotion group (Hl, 0.12g /kg, n = 20); Hm group was the Medium dosing of Huangqi decotion group (Hm, 0.36g/kg, n = 20); HH group was the High dosing of Huangqi decotion group (HH, 1.08g/kg, n = 20). Sh: Sham group; En: Enalapri group; Nx: 5/6 nephrectomy model group; Hh: High dosing of Huangqi decotion group; Hm: Medium dosing of Huangqi decotion group; Hl: Low dosing of Huangqi decotion group. aP < 0.05, compared with Sham group; bP < 0.01 or cP < 0.05, compared with Nx group, n = 8-11.
Figure 3 Huangqi treatment attenuates renal damage in a dosage-dependent manner in Nx mice A: representative PAS-stained kidney sections from Sham, Nx, enalapril, Hl, Hm, Hh groups; B: histopathological scores and inflammatory cells count within the tubulointerstitium from sections similar to those shown in (A); C: representative Masson's modified trichrome stained kidney sections from Sham, Nx, enalapril, Hl, Hm, Hh groups; D: quantitative analysis of the extent of renal interstitial expansion (area %) from sections similar to those shown in. Sh group was the control group; Nx group was the 5/6 nephrectomy model group; En group was the control group by Enalapri; Hl group was the Low dosing of Huangqi decotion group (Hl, 0.12g /kg, n = 20); Hm group was the Medium dosing of Huangqi decotion group (Hm, 0.36g/kg, n = 20); HH group was the High dosing of Huangqi decotion group (HH, 1.08g/kg, n = 20). Sh: Sham group; En: Enalapri group; Nx: 5/6 nephrectomy model group; Hh: High dosing of Huangqi decotion group; Hm: Medium dosing of Huangqi decotion group; Hl: Low dosing of Huangqi decotion group. aP < 0.05, compared with Sham group; bP < 0.01 or cP < 0.05, compared with Nx group, n = 8-11. Magnification: (× 400).
Figure 4 Huangqi decoction decreases the Nx kidneys' CTGF and Collagen III expression by immunohistochemistry A, C: representative photomicrographs of CTGF and Collagen III immunohistochemistry on kidney sections from the Sham, Nx, enalapril, Hl, Hm, Hh groups; B, D: quantitative analysis of CTGF and Collagen III expression from sections similar to those shown in A, C. Sh group was the control group; Nx group was the 5/6 nephrectomy model group; En group was the control group by Enalapri; Hl group was the Low dosing of Huangqi decotion group (Hl, 0.12g /kg, n = 20); Hm group was the Medium dosing of Huangqi decotion group (Hm, 0.36g/kg, n = 20); HH group was the High dosing of Huangqi decotion group (HH, 1.08g/kg, n = 20). Sh: Sham group; En: Enalapri group; Nx: 5/6 nephrectomy model group; Hh: High dosing of Huangqi decotion group; Hm: Medium dosing of Huangqi decotion group; Hl: Low dosing of Huangqi decotion group. aP < 0.05, compared with Sham group; bP < 0.01 or cP < 0.05, compared with Nx group, n = 8-11. Magnification: (× 400).
Figure 5 Huangqi decotion alleviates matrix accumulation in Nx kidneys A: protein expressions of TGF-β1, FSP-1 and α-SMA by Western Blot; B-D: statistical analyses versus A. E: representative photomicrographs of FSP-1by immunohistochemistry on kidney sections from the Sham, Nx, enalapril, Hl, Hm, Hh groups; F: quantitative analysis of FSP-1 expression from sections similar to those shown in E. Sh group was the control group; Nx group was the 5/6 nephrectomy model group; En group was the control group by Enalapri; Hl group was the Low dosing of Huangqi decotion group (Hl, 0.12g /kg, n = 20); Hm group was the Medium dosing of Huangqi decotion group (Hm, 0.36g/kg, n = 20); HH group was the High dosing of Huangqi decotion group (HH, 1.08g/kg, n = 20).Sh: Sham group; En: Enalapri group; Nx: 5/6 nephrectomy model group; Hh: High dosing of Huangqi decotion group; Hm: Medium dosing of Huangqi decotion group; Hl: Low dosing of Huangqi decotion group. aP < 0.05, compared with Sham grou;. bP < 0.01 or cP < 0.05, compared with Nx group, n = 8-11. Magnification: (× 400).
Figure 6 Huangqi decotion downregulats MAPK signaling pathway on kidney sections A: protein expressions of P-P38, P-JNK, P-ERK, Bax and Bcl-2 by Western Blot; B-F: statistical analyses versus A. Sh group was the control group; Nx group was the 5/6 nephrectomy model group; En group was the control group by Enalapri; Hl group was the Low dosing of Huangqi decotion group (Hl, 0.12g /kg, n = 20); Hm group was the Medium dosing of Huangqi decotion group (Hm, 0.36g/kg, n = 20); HH group was the High dosing of Huangqi decotion group (HH, 1.08g/kg, n = 20).Sh: Sham group; En: Enalapri group; Nx: 5/6 nephrectomy model group; Hh: High dosing of Huangqi decotion group; Hm: Medium dosing of Huangqi decotion group; Hl: Low dosing of Huangqi decotion group. aP < 0.05, compared with Sham group. bP < 0.01 or cP < 0.05, compared with Nx group, n = 8-11.
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