Search JIM Advanced Search

Journal of Chinese Integrative Medicine ›› 2005, Vol. 3 ›› Issue (6): 459-462.doi: 10.3736/jcim20050610

• Original Clinical Research • Previous Articles     Next Articles

Protective effects of Salvia miltiorrhiza on rats with streptozotocin diabetes and its mechanism

Gang Liu1,Guang-ju Guan1,Tong-gang Qi2,Yu-qin Fu1,Xue-gang Li1,Yun Sun1,Tao Wu1,Rong-zhu Wen1   

  1. 1. Department of Nephrology, Second Hospital, Shandong University, Jinan, Shandong Province 250033, China
    2. Laboratory of Molecular Biology, Second Hospital, Shandong University, Jinan, Shandong Province 250033, China
  • Received:2005-04-21 Online:2005-11-20 Published:2005-11-20
  • Contact: Guang-Ju GUAN E-mail:guangj@sdu.edu.cn

Objective

To explore the effects of Salvia miltiorrhiza on renal morphology and renal function of rats with streptozotocin diabetes.

Methods

Thirty male Wistar rats were randomly divided into three groups, which were normal control group, untreated group and Salvia miltiorrhiza-treated group. Diabetic nephropathy was induced in rats of the last two groups by intraperitoneal injection of streptozotocin after unilateral nephrectomy. Then the rats in the normal control and untreated groups were fed with normal saline while those in the Salvia miltiorrhiza-treated group were fed Salvia miltiorrhiza preparation for 8 weeks. The glomerular volume (VG), kidney-to-body weight ratio (KW/BW), urinary albumin excretion rate (UAER) and creatinine clearance (Ccr) were observed. The expression levels of transforming growth factor-beta1 (TGF-β1), connective tissue growth factor (CTGF), fibronectin (FN) and plasminogen activator inhibitor-1 (PAI-1) were detected by real-time quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) at the end of the experiment.

Results

UAER, Ccr, VG and KW/BW ratio were significantly higher in the untreated group than those in the normal control group (P<0.05). The expression levels of TGF-β1, CTGF, PAI-1 and FN in the untreated group were also significantly higher as compared with those in the normal control group (P<0.05). UAER, Ccr, VG, KW/BW ratio and the levels of TGF-β1, CTGF, PAI-1 and FN in the Salvia miltiorrhiza-treated group were obviously lower than those in the untreated group (P<0.05).

Conclusion

Salvia miltiorrhiza can protect rats with streptozotocin diabetes from diabetic nephropathy by suppressing the over-expressions of TGF-β1, CTGF, PAI-1 and FN in renal cortex.

Key words: Streptozotocin diabetes, Salvia miltiorrhiza, Transforming growth factor-beta1, Connective tissue growth factor, Plasminogen activator inhibitor-1

CLC Number: 

  • R587.1

Tab 1

Primers for quantitative real-time PCR"

Target gene Primer sequence Amplified fragment length
CTGF sense 5’ AGA ACT GTG CAC GGA GCG TG 3’ 526 bp
antisense 5’CCT GAC CAT TCA GAG ACG AC 3’
TGF-β1 sense 5’GCC TCC GCA TCC CAC CTT TG 3’ 396 bp
antisense 5’GCG GGT GAC TTC TTT GGC GT 3’
PAI-1 sense 5’ATG AGA TCA GTA CTG CGG ACG CCA TCT TTG 3’ 333 bp
antisense 5’GCA CGG AGA TGG TGC TAC CAT CAG ACT TGT 3’
FN sense 5’TTA TGA CGA TGG GAA GAC CTA 3’ 295 bp
antisense 5’GTG GGG CTG GAA AGA TTA CTC 3’
GAPDH sense 5’ACC ACA GTC CAT GCC ATC AC 3’ 450 bp
antisense 5’TCC ACC ACC CTG TTG CTG TA 3’

Tab 2

Changes of body weight and blood glucose level of rats in 3 groups ($\bar{x}$±s )"

Group n Body weight (g) Blood glucose (mmol/L)
4th week 8th week 4th week 8th week
Normal control 10 275.6±19.8 344.2±20.6 4.52±0.32 4.88±0.39
Untreated 9 229.3±14.5* 241.8±16.9* 21.60±2.83* 22.65±2.97*
Salvia miltiorrhiza-treated 9 218.6±13.1* 246.4±15.2* 20.75±2.33* 21.49±3.12*

Tab 3

Renal morphology and renal function of rats in 3 groups ($\bar{x}$±s )"

Group n KW/BW (×10-3) VG (×106 μm3) UAER (mg/24 h) Ccr (ml·min–1·100 g-1
Normal control 10 3.6±0.2 0.48±0.06 0.28±0.05 0.52±0.04
Untreated 9 9.4±0.8* 1.16±0.18* 5.47±0.42* 0.95±0.16*
Salvia miltiorrhiza-treated 9 7.0±0.5* 0.80±0.05* 3.25±0.19* 0.76±0.06*

Tab 4

Expression levels of TGF-β1, CTGF, PAI-1 and FN in kidney cortex of rats in 3 groups ($\bar{x}$±s )"

Group n TGF-β1 CTGF PAI-1 FN
Normal control 10 0.309±0.081 0.394±0.060 0.209±0.056 0.462±0.082
Untreated 9 4.820±0.241* 1.827±0.352* 0.981±0.317* 3.134±0.516*
Salvia miltiorrhiza-treated 9 2.014±0.121* 1.309±0.223* 0.509±0.084* 1.948±0.253*
[1] Molitch ME , DeFronzo RA, Franz MJ, et al.Nephropathy in diabetes[J]. Diabetes Care, 2004,27(Suppl 1):S79-S83
doi: 10.2337/diacare.27.2007.S79
[2] Eikmans M , Baelde JJ, de Heer E, et al.ECM homeostasis in renal diseases: a genomic approach[J]. J Pathol, 2003,200(4):526-536
doi: 10.1002/path.1417
[3] Wolf G . Growth factors and the development of diabetic nephropathy[J]. Curr Diab Rep, 2003,3(6):485-490
doi: 10.1007/s11892-003-0012-2
[4] 柳刚, 关广聚 . 结缔组织生长因子与糖尿病肾病[J]. 中国中西医结合肾病杂志, 2004,5(5):305-307
[5] Duncan MR, Frazier KS, Abramson S , et al. Connective tissue growth factor mediates transforming growth factor beta-induced collagen synjournal: down-regulation by cAMP[J]. FASEB J, 1999,13(13):1774-1786
doi: 10.1096/fasebj.13.13.1774
[6] Ito Y, Bende RJ, Oemar BS , et al. Expression of connective tissue growth factor in human renal fibrosis[J]. Kidney Int, 1998,53(4):853-861
doi: 10.1111/j.1523-1755.1998.00820.x
[7] Riser BL, Cortes P . Connective tissue growth factor and its regulation: a new element in diabetic glomerulosclerosis[J]. Ren Fail, 2001,23(3-4):459-470
doi: 10.1081/JDI-100104729
[8] Rerolle JP, Hertig A, Nguyen G , et al. Plasminogen activator inhibitor type 1 is a potential target in renal fibrogenesis[J]. Kidney Int, 2000,58(5):1841-1850
doi: 10.1111/j.1523-1755.2000.00355.x
[9] 孙玉凤, 姚希贤, 蒋树林 . 肝纤维化的中医中药研究[J]. 世界华人消化杂志, 2000,8(6):686-687
[10] 彭佑铭, 刘伏友, 罗季安 , 等. 丹参及生脉液对阿霉素所致大鼠肾小球硬化的实验性治疗作用[J]. 湖南医科大学学报, 1999,24(4):332-334
[11] 王晓玲, 刘平, 刘成海 , 等. 丹酚酸A对成纤维细胞活力、增殖及胶原合成的影响[J]. 中西医结合肝病杂志, 2000,10(1):24-25
[12] 林琼真, 于洁, 邓英辉 , 等. 丹参注射液对大鼠梗阻性肾间质纤维化的保护作用[J]. 中国中西医结合肾病杂志, 2003,4(2):71-73
[1] Qing-lan Wang, Yan-yan Tao , Li Shen , Hong-yan Cui , Cheng-hai Liu. Chinese herbal medicine Fuzheng Huayu recipe inhibits liver fibrosis by mediating the transforming growth factor-β1/Smads signaling pathway. Journal of Chinese Integrative Medicine, 2012, 10(5): 561-568.
[2] Yong-mei Liu, Rui-hua Liu, Wen-jun Liu, Li Liu , Zhi-kui Wu, Yu-ying Chen. Effects of Chinese herbal medicine Yiqi Huoxue Formula on TGF-p/smad signal transduction pathway and connective tissue growth factor in rats with renal interstitial fibrosis. Journal of Chinese Integrative Medicine, 2010, 8(12): 1165-1173.
[3] Jun-ming Chen, Lei Wang, Tao Liu, Lian-jun Xing, Pei-yong Zheng, Guang Ji. Effects of Qinggan Huoxue Recipe and its separated recipes on urokinase-type plasminogen activator and plasminogen activator inhibitor-1 fibrinolytic system in rats with alcoholic liver fibrosis. Journal of Chinese Integrative Medicine, 2009, 7(7): 642-650.
[4] Ya-hui Liang, Ping Li , Qi-fu Huang , Jing-xia Zhao , Xin Liu , Miao-ke Dai. Salvianolic acid B in vitro inhibited matrix metalloproteinases-1, -2, and -9 activities. Journal of Chinese Integrative Medicine, 2009, 7(2): 145-150.
[5] Bin Zhang, Ling-tai Wang. Bushen Rougan Recipe in prevention of hepatic fibrosis in rats induced by dimethylnitrosamine: a study on its preliminary mechanism. Journal of Chinese Integrative Medicine, 2008, 6(9): 934-938.
[6] Ji-hong Chen, Wei Sun, Dong Zhou, Kun Gao, Wei-ming He, Li Liu. Effects of Dahuang Zhechong Pill on expressions of tissue inhibitor of metalloproteinase-1 and plasminogen activator inhibitor-1 in rats with glomerulosclerosis. Journal of Chinese Integrative Medicine, 2008, 6(5): 512-516.
[7] Dan Zhang, Jing Shu, Yi Wang. Salvia Miltiorrhiza injection relieves peritoneal dialysis solution-induced injuries of peritoneal structure and function in rats. Journal of Chinese Integrative Medicine, 2008, 6(5): 517-523.
[8] Zong-jiang Zhao, Qi Qiu, Xin-xue Zhang, Mei-juan Yang. Effect of compound Biejia Ruangan tablet on expressions of connective tissue growth factor mRNA and protein in kidney tissue of rats with adriamycin-induced nephropathy. Journal of Chinese Integrative Medicine, 2007, 5(6): 651-655.
[9] ZHOU Yang, GU Jie, XU Lie-ming. Effect and mechanism of salvianolic acid B in attenuating elevated portal pressure in a rat model of portal hypertension induced by endothelin-1. Journal of Chinese Integrative Medicine, 2007, 5(1): 61-64.
[10] Guo-lin Peng, Xiao-yun Zhang. Effects of Salvia miltiorrhiza on serum levels of inflammatory cytokines in patients with severe acute pancreatitis. Journal of Chinese Integrative Medicine, 2007, 5(1): 28-31.
[11] Xue-lin He​, Jian-ping Li​, Yi-ping Chen​, Zhi-gang Zhang​, Wei-qin Lin​, Jiang-hua Chen​. Effects of Tangshenling Mixture and benazepril on rats with diabetic nephropathy and its mechanism. Journal of Chinese Integrative Medicine, 2006, 4(1): 43-47.
Viewed
Full text


Abstract

Cited

  Shared   
  Discussed   
[1] Jin-zhou Tian, Jing Shi, Xin-qing Zhang, Qi Bi, Xin Ma, Zhi-liang Wang, Xiao-bin Li, Shu-li Shen, Lin Li, Zhen-yun Wu, Li-yan Fang, Xiao-dong Zhao, Ying-chun Miao, Peng-wen Wang, Ying Ren, Jun-xiang Yin, Yong-yan Wang, Beijing United Study Group on MCI of the Capital Foundation of Medical Developments. An explanation on "guiding principles of clinical research on mild cognitive impairment (protocol)". Journal of Chinese Integrative Medicine, 2008, 6(1): 15-21
[2] Yi-ting He, Qing-lin Zha, Jian-ping Yu, Yong Tan, Cheng Lu, Ai-ping Lv. Principal factor analysis of symptoms of rheumatoid arthritis and their correlations with efficacy of traditional Chinese medicine and Western medicine. Journal of Chinese Integrative Medicine, 2008, 6(1): 32-36
[3] Jun Cai, Hua Wang, Sheng Zhou, Bin Wu, Hua-rong Song, Zheng-rong Xuan. Effect of Sijunzi Decoction and enteral nutrition on T-cell subsets and nutritional status in patients with gastric cancer after operation: A randomized controlled trial. Journal of Chinese Integrative Medicine, 2008, 6(1): 37-40
[4] Wei Zhang, Xiang-feng Lu, Xiao-mei Zhang, Jian-jun Wu, Liang-duo Jiang. A rat model of pulmonary fibrosis induced by infusing bleomycin quickly through tracheal intubation. Journal of Chinese Integrative Medicine, 2008, 6(1): 60-67
[5] A-gao Zhou, Yong Zhang, Gang Kui, De-Yun Kong, Hai-liang Ge, Qiu-hua Ren, Jia-rong Dong, Sheng Hong, Xu-ming Mao, Yin Wang, Hui-zheng Zhang, Shu-jun Wang. Influence of traditional Chinese compound recipes with different efficacy on body weight, tumor weight and immune function in H22 cancer-bearing mice. Journal of Chinese Integrative Medicine, 2008, 6(1): 77-82
[6] Guo-hong Yuan, Xiao-jing Pang, He-chao Ma. Synergic effects of Danggui Buxue Decoction in reducing toxicity of cytoxan in tumor-bearing mice. Journal of Chinese Integrative Medicine, 2008, 6(1): 83-88
[7] Li Zhou, Hong-xing Zhang, Ling-guang Liu, Wen-jun Wan. Effect of electro-acupuncture at Fenglong (GV 16) on nitric oxide and endothelin in rats with hyperlipidemia. Journal of Chinese Integrative Medicine, 2008, 6(1): 89-92
[8] Jin-zhou Tian, Jing Shi, Xin-qing Zhang, Qi Bi, Xin Ma, Zhi-liang Wang, Xiao-bin Li, Shu-li Shen, Lin Li, Zhen-yun Wu, Li-yan Fang, Xiao-dong Zhao, Ying-chun Miao, Peng-wen Wang, Ying Ren, Jun-xiang Yin, Yong-yan Wang, Beijing United Study Group on MCI of the Capital Foundation of Medical Developments. Guiding principles of clinical research on mild cognitive impairment (protocol). Journal of Chinese Integrative Medicine, 2008, 6(1): 9-14
[9] Xin-jun Wang, Ling-ling Wang . A mechanism of endogenous opioid peptides for rapid onset of acupuncture effect in treatment of depression. Journal of Chinese Integrative Medicine, 2010, 8(11): 1014-1017
[10] Bo Wang , Wei Yan , Li-hui Hou, Xiao-ke Wu. Disorder of Tiangui (kidney essence) and reproductive dysfunction in patients with polycystic ovary syndrome. Journal of Chinese Integrative Medicine, 2010, 8(11): 1018-1022