Search JIM Advanced Search

Journal of Chinese Integrative Medicine ›› 2008, Vol. 6 ›› Issue (5): 493-497.doi: 10.3736/jcim20080512

• Original Experimental Research • Previous Articles     Next Articles

Dilingdan Decoction prevents renal interstitial fibrosis in a rat model of unilateral ureteral obstruction

Hong-di Huan(), Jing-hong Zhang, Shi-rong Zheng, Wei-wei Meng, Jun-li Zhang   

  1. Department of Nephrology, the 85th Hospital of Peoples Liberation Army, Shanghai 200052, China
  • Received:2008-03-14 Online:2008-05-20 Published:2008-05-15
  • Contact: HUAN Hong-di

Objective: To investigate the preventive and therapeutic effects and the possible mechanisms of Dilingdan Decoction (DLDD), a compound Chinese herbal medicine, on rats with renal tubulointerstitial fibrosis induced by unilateral ureteral obstruction (UUO).
Methods: Sixty SD rats were randomly divided into sham-operated group, untreated group, enalapril-treated group and DLDD-treated group. Blood urea nitrogen (BUN), serum creatinine (SCr), urine protein quantization in 24 hours and pathological changes of the obstructed kidney were observed. The expressions of transforming growth factor-β1 (TGF-β1), alpha-smooth muscle actin (α-SMA), fibronectin (FN) and laminin (LN) were detected by immunohistochemical method and colored-multimedia pathological image analysis system.
Results: Massive inflammatory infiltrates and collagen expression in renal interstitial in the untreated group were observed on the 7th day. Compared with the sham-operated group, percentages of area of TGF-β1, α-SMA, FN and LN expressions in the untreated group were markedly increased (P<0.05), while the percentage of area of interstitial fibrosis was decreased in the DLDD-treated group as compared with the untreated group (P<0.05). On the 14th day, the percentages of area of TGF-β1, α-SMA, FN and LN expressions were declined in two treated groups as compared with the untreated group (P<0.05), but had no statistical difference in biochemical indicators, including BUN, SCr and 24-hour urinary protein. On the 21st day, the level of SCr and the percentage of area of TGF-β1 expression in the DLDD-treated group were lower than those of the enalapril-treated group (P<0.05).
Conclusion: DLDD can reduce the excretion of urinary protein and the degree of interstitial fibrosis, and significantly inhibit the expressions of TGF-β1, α-SMA, FN and LN. DLDD is superior to enalapril in protecting renal function after long-time application in rats.

Key words: Dilingdan Decoction, renal interstitial fibrosis, transforming growth factor-betal, alpha-smooth muscle actin, fibronectin, laminin, rats

CLC Number: 

  • R692.6


Results of BUN, SCr, and urine protein quantization in 24 hours in different groups ($\bar{x}$±s)"

Group n BUN (mmol/L) SCr (mmol/L) 24 h urine protein (mg/24 h)
Day 7 6 4.15±2.61 21.83±7.60 5.79±0.98
Day 7 6 4.57±0.57 24.33±2.73 5.81±2.30
Day 14 6 5.48±0.20 41.33±5.47 12.74±3.55
Day 21 6 6.18±0.72 68.00±17.11 12.64±4.77
Day 7 6 5.12±0.30 31.83±11.25 4.45±1.09
Day 14 6 5.58±0.44 55.50±26.85 11.02±3.48
Day 21 6 10.90±1.00 49.00±31.48 6.06±1.53
Day 7 6 4.62±0.42 32.33±16.05 5.37±2.41
Day 14 6 6.30±1.15 50.67±4.97 9.52±7.96
Day 21 6 9.73±1.45 32.83±9.26△▲ 6.06±3.20

Table 2

Percentages of interstitial fibrosis area in rats in different groups ($\bar{x}$±s, %)"

Group n Fibrosis area
Day 7 Day 14 Day 21
Sham-operated 6 0.66±0.49
Untreated 6 4.18±2.46* 3.06±1.03 4.87±0.71
Enalapril-treated 6 3.07±0.37* 1.46±0.61 2.26±1.47
DLDD-treated 6 2.38±0.70* 2.34±0.79 1.85±0.45△▲

Table 3

Percentages of area of TGF-β1 and α-SMA expressions in renal interstitium in different groups ($\bar{x}$±s, %)"

Group n TGF-β1 α-SMA
Day 7 Day 14 Day 21 Day 7 Day 14 Day 21
Sham-operated 6 4.82±1.61 1.64±0.61
Untreated 6 11.09±2.70* 9.73±0.70 9.76±2.26 9.00±1.69 9.85±1.72 12.46±2.49
Enalapril-treated 6 8.08±1.88 5.37±2.77 3.35±1.52 5.63±1.67 7.31±1.78 7.41±1.72
DLDD-treated 6 8.49±1.99 6.18±1.80 3.21±1.38△▲ 5.79±1.93 5.11±1.54△▲ 7.05±1.82

Table 4

Percentages of area of FN and LN expressions in renal interstitium in different groups ($\bar{x}$±s, %)"

Group n FN LN
Day 7 Day 14 Day 21 Day 7 Day 14 Day 21
Sham-operated 6 4.82±1.02 2.13±0.81
Untreated 6 11.99±2.00* 13.16±1.99 14.46±0.73 10.20±2.23* 12.87±2.15 13.78±2.76
Enalapril-treated 6 8.09±1.88 6.30±1.02 8.04±2.13 7.19±1.19 8.91±2.85 9.78±2.01
DLDD-treated 6 6.99±2.66 6.93±1.75 7.62±1.97 7.20±1.23 8.84±2.56 9.03±2.81
[1] Yang J, Liu Y . Dissection of key events in tubular epithelial to myofibroblast transition and its implications in renal interstitial fibrosis[J]. Am J Pathol, 2001,159(4):1465-1475
doi: 10.1016/S0002-9440(10)62533-3
[2] Gagliardini E, Benigni A . Role of anti-TGF-beta antibodies in the treatment of renal injury[J]. Cytokine Growth Factor Rev, 2006,17(1-2):89-96
doi: 10.1016/j.cytogfr.2005.09.005 pmid: 16257566
[3] You SX. Medical experimental methods of animals[M]. Beijing: People's Medical Publishing House, 1980: 103
猷施新 . 医学动物实验方法[M]. 北京: 人民卫生出版社, 1980: 103
[4] Wang G, Chen YP, Zou YQ. Current nephrology of traditional Chinese medicine[M]. Beijing: People's Medical Publishing House, 2003: 1057
王刚, 陈以平, 邹燕勤 . 现代中医肾脏病学[M]. 北京: 人民卫生出版社, 2003: 1057
[5] Lu ZL, Wang XQ . Comments on the pathogenesis of renal interstitial fibrosis[J]. Hubei Zhong Yi Za Zhi, 2004,26(11):18-19
doi: 10.3969/j.issn.1000-0704.2004.11.009
卢祖礼, 王小琴 . 浅析肾纤维化的中医病机[J]. 湖北中医杂志, 2004,26(11):18-19
doi: 10.3969/j.issn.1000-0704.2004.11.009
[6] Zheng SR, Zhu YQ, Cai G , et al. Effect of Dilingdan compound on renal function and histological changes in diabetic rats[J]. Zhong Yi Yao Yan Jiu, 1996,( 1):51-53
郑士荣, 朱宇清, 蔡淦 , 等. 地灵丹对糖尿病大鼠肾脏功能及组织病理学改变的影响[J]. 中医药研究, 1996,( 1):51-53
[7] Zheng SR, Cai G, Zhu YQ , et al. Effect of Dilingdan compound on neuro-endocrine system in diabetic rats[J]. Zhong Yi Yao Yan Jiu, 1997,13(5):52-54
郑士荣, 蔡淦; 朱宇清, 等. 地灵丹对糖尿病大鼠神经内分泌系统的调节作用[J]. 中医药研究, 1997,13(5):52-54
[8] Pantsulaia T . Role of TGF-beta in pathogenesis of diabetic nephropathy[J]. Georgian Med News, 2006,( 131):13-18
doi: 10.1159/000060149 pmid: 16575121
[9] Masszi A, Fan L, Rosivall L , et al. Integrity of cell-cell contacts is a critical regulator of TGF-beta 1-induced epithelial-to-myofibroblast transition: role for beta-catenin[J]. Am J Pathol, 2004,165(6):1955-1967
doi: 10.1016/S0002-9440(10)63247-6
[10] Quan G, Choi JY, Lee DS , et al. TGF-beta1 up-regulates transglutaminase two and fibronectin in dermal fibroblasts: a possible mechanism for the stabilization of tissue inflammation[J]. Arch Dermatol Res, 2005,297(2):84-90
doi: 10.1007/s00403-005-0582-8
[1] Bing-rong Li, Shi-yun Shao, Long Yuan, Ru Jia, Jian Sun, Qing Ji, Hua Sui, Li-hong Zhou, Yi Zhang, Hui Liu, Qi Li, Yan Wang, Bi-meng Zhang. Effects of mild moxibustion on intestinal microbiome and NLRP3 inflammasome in rats with 5-fluorouracil-induced intestinal mucositis. Journal of Integrative Medicine, 2021, 19(2): 144-157.
[2] Qing-lan Wang, Yan-yan Tao, Hong-dong Xie, Cheng-hai Liu, Ping Liu. Fuzheng Huayu recipe, a traditional Chinese compound herbal medicine, attenuates renal interstitial fibrosis via targeting the miR-21/PTEN/AKT axis. Journal of Integrative Medicine, 2020, 18(6): 505-513.
[3] Sitthichai Iamsaard, Supatcharee Arun, Jaturon Burawat, Supataechasit Yannasithinon, Saranya Tongpan, Sudtida Bunsueb, Natthapol Lapyuneyong, Pannawat Choowong-in, Nareelak Tangsrisakda, Chadaporn Chaimontri, Wannisa Sukhorum. Evaluation of antioxidant capacity and reproductive toxicity of aqueous extract of Thai Mucuna pruriens seeds. Journal of Integrative Medicine, 2020, 18(3): 265-273.
[4] Morufu Eyitayo Balogun, Elizabeth Enohnyaket Besong, Jacinta Nkechi Obimma, Ogochukwu Sophia Mbamalu, Fankou Serges Athanase Djobissie. Protective roles of Vigna subterranea (Bambara nut) in rats with aspirin-induced gastric mucosal injury. Journal of Integrative Medicine, 2018, 16(5): 342-349.
[5] Lucky Legbosi Nwidu, Raphael Ellis Teme. Hot aqueous leaf extract of Lasianthera africana (Icacinaceae) attenuates rifampicin-isoniazid-induced hepatotoxicity. Journal of Integrative Medicine, 2018, 16(4): 263-272.
[6] JiaXia, Li-qunHe, XiaoSu. Interventional mechanisms of herbs or herbal extracts on renal interstitial fibrosis. Journal of Integrative Medicine, 2016, 14(3): 165-173.
[7] Kylie Connolly, Douglas Jackson, Candice Pullen, Andrew Fenning. Alpha-adrenoceptor antagonism by Crassostrea gigas oyster extract inhibits noradrenaline-induced vascular contraction in Wistar rats. Journal of Integrative Medicine, 2015, 13(3): 194-200.
[8] Udhaya Lavinya Baskaran, Sherry Joseph Martin, Rasool Mahaboobkhan, Sabina Evan Prince. Protective role of Triphala, an Indian traditional herbal formulation, against the nephrotoxic effects of bromobenzene in Wistar albino rats. Journal of Integrative Medicine, 2015, 13(2): 115-121.
[9] Hussein O. B. Oloyede, Matthew C. Adaja, Taofeek O. Ajiboye, Musa O. Salawu. Anti-ulcerogenic activity of aqueous extract of Carica papaya seed on indomethacin-induced peptic ulcer in male albino rats. Journal of Integrative Medicine, 2015, 13(2): 105-114.
[10] Anirudha A. Lande, Shirishkumar D. Ambavade, Uma S. Swami, Prafulla P. Adkara Prashant D. Ambavade, Arun B. Waghamare. Saponins isolated from roots of Chlorophytum borivilianum reduce acute and chronic inflammation and histone deacetylase. Journal of Integrative Medicine, 2015, 13(1): 25-33.
[11] Elizabeth Abidemi Balogun, Sylvia Orume Malomo, Joseph Oluwatope Adebayo, Ahmed Adebayo Ishola, Ayodele Olufemi Soladoye, Lawrence Aderemi Olatunji, Olatunji Matthew Kolawole, Stephen Olubunmi Oguntoye, Abiola Samuel Babatunde, Oluwole Busayo Akinola . In vivo antimalarial activity and toxicological effects of methanolic extract of Cocos nucifera (Dwarf red variety) husk fibre. Journal of Integrative Medicine, 2014, 12(6): 504-511.
[12] Urmila Aswar, Mayuri Gurav, Ganesh More, Khaled Rashed, Manoj Aswar. Effect of aqueous extract of Solanum xanthocarpum Schrad. & Wendl. on postmenopausal syndrome in ovariectomized rats. Journal of Integrative Medicine, 2014, 12(5): 439-446.
[13] Xin-fang Zhang, Ji Zhu, Wen-ye Geng, Shu-jun Zhao, Chuan-wei Jiang, Sheng-rong Cai, Miao Cheng, Chuan-yun Zhou, Zi-bing Liu. Electroacupuncture at Feishu (BL13) and Zusanli (ST36) down-regulates the expression of orexins and their receptors in rats with chronic obstructive pulmonary disease. Journal of Integrative Medicine, 2014, 12(5): 417-424.
[14] Benjamin Perry, Junzeng Zhang, Tarek Saleh, Yanwen Wang. Liuwei Dihuang, a traditional Chinese herbal formula, suppresses chronic inflammation and oxidative stress in obese rats. Journal of Integrative Medicine, 2014, 12(5): 447-454.
[15] Upendarrao Golla, Praveen Kumar Gajam, Solomon Sunder Bhimathati. Evaluation of diuretic and laxative activity of hydro-alcoholic extract of Desmostachya bipinnata (L.) Stapf in rats. Journal of Integrative Medicine, 2014, 12(4): 372-378.
Full text



[1] Dong Yang, Yong-ping Du, Qing Shen, Wei Chen, Yan Yu, Guang-lei Chen. Expression of alpha-smooth muscle actin in renal tubulointerstitium in patients with kidney collateral stasis. Journal of Chinese Integrative Medicine, 2008, 6(1): 41-44
[2] Hai-feng Wei, Bai-liu Ya, Ling Zhao, Cui-fei Ye, Li Zhang, Lin Li. Evaluation of tongue manifestation of blood stasis syndrome and its relationship with blood rheological disorder in a rat model of transient brain ischemia. Journal of Chinese Integrative Medicine, 2008, 6(1): 73-76
[3] Xi Lin, Jian-ping Liu. Herbal medicines for viral myocarditis. Journal of Chinese Integrative Medicine, 2008, 6(1): 76
[4] Xi Lin, Jian-ping Liu. Tai chi for treating rheumatoid arthritis. Journal of Chinese Integrative Medicine, 2008, 6(1): 82
[5] Liang-ping Hu, Hui Gao. Discrimination of errors in statistical analysis of medical papers published in the first issue of 2006 in Journal of Chinese Integrative Medicine. Journal of Chinese Integrative Medicine, 2008, 6(1): 98-106
[6] Yan-bo Zhu , Qi Wang, Cheng-yu Wu, Guo-ming Pang, Jian-xiong Zhao, Shi-lin Shen, Zhong-yuan Xia , Xue Yan . Logistic regression analysis on relationships between traditional Chinese medicine constitutional types and overweight or obesity. Journal of Chinese Integrative Medicine, 2010, 8(11): 1023-1035
[7] Wei Xu, Meng Shi, Jian-gang Liu, Cheng-long Wang . Collagen protein expressions in ischemic myocardium of rats with acute myocardial infarction and effects of qi-tonifying, yin-tonifying and blood-activating herbs and detoxifying and blood-activating herbs. Journal of Chinese Integrative Medicine, 2010, 8(11): 1041-1047
[8] Tao Wang , Feng Qin. Effects of Chinese herbal medicine Xiaoyao Powder on monoamine neurotransmitters in hippocampus of rats with postpartum depression. Journal of Chinese Integrative Medicine, 2010, 8(11): 1075-1079
[9] Ying Xu , Chang-chun Zeng , Xiu-yu Cai , Rong-ping Guo , Guang Nie , Ying Jin. Chromaticity and optical spectrum colorimetry of the tongue color in different syndromes of primary hepatic carcinoma. Journal of Chinese Integrative Medicine, 2012, 10(11): 1263-1271
[10] Xiang-ying Mao , Qin Bian , Zi-yin Shen. Analysis of the osteogenetic effects exerted on mesenchymal stem cell strain C3H10T1/2 by icariin via MAPK signaling pathway in vitro. Journal of Chinese Integrative Medicine, 2012, 10(11): 1272-1278