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Journal of Chinese Integrative Medicine ›› 2009, Vol. 7 ›› Issue (5): 434-440.doi: 10.3736/jcim20090507

• Original Experimental Research • Previous Articles     Next Articles

Effects of Radix et Rhizoma Rhodiolae Kirilowii on expressions of von Willebrand factor, hypoxia-inducible factor 1 and vascular endothelial growth factor in myocardium of rats with acute myocardial infarction

Xiu-fang Gaoa,Hai-ming Shia,Tao Suna,Hong Aob   

  1. a Department of Cardiology, Huashan Hospital, Fudan University, Shanghai 200040, China
    b Department of Animal Research, Fudan University, Shanghai 200032, China
  • Received:2008-10-29 Accepted:2008-12-25 Online:2009-05-20 Published:2009-05-15

Objective

To investigate the effects of Radix et Rhizoma Rhodiolae Kirilowii on angiogenesis and expressions of hypoxia-inducible factor 1α (HIF-1α), hypoxia-inducible factor 1β (HIF-1β) and vascular endothelial growth factor (VEGF) in myocardium of rats with acute myocardial infarction (AMI), to elucidate the possible mechanism of Radix et Rhizoma Rhodiolae Kirilowii in promoting angiogenesis, and to investigate that whether or not salidroside could be considered as the effective component of Radix et Rhizoma Rhodiolae Kirilowii with regard to the effects mentioned above.
Methods

Thirty-six male Wistar rats had the anterior descending branch of coronary artery ligated as AMI model. Rats were fed with normal saline (untreated group), Radix et Rhizoma Rhodiolae Kirilowii solution (Radix et Rhizoma Rhodiolae Kirilowii group) or salidroside solution (salidroside group) from 7 days before until 7 days after the operation, with twelve rats in each group. All rats were sacrificed 7 days after the operation. Immunohistochemical assay (IHC) was used for detecting the expression of von Willebrand factor (vWF); TaqMan real-time quantitative polymerase chain reaction (PCR) assay was employed for detection of the levels of HIF-1α, HIF-1β and VEGF mRNAs; Western blot analysis was used for detection of the corresponding protein levels.
Results

Results of IHC index showed that both at infarct border zone and non-infarct zone, the expressions of vWF were significantly increased in Radix et Rhizoma Rhodiolae Kirilowii group as compared with the untreated group (P<0.05). The expressions of HIF-1α, HIF-1β and VEGF mRNAs and the expressions of HIF-1α and VEGF proteins were significantly increased in the Radix et Rhizoma Rhodiolae Kirilowii group as compared with the untreated group (P<0.01). The level of HIF-1β protein in the Radix et Rhizoma Rhodiolae Kirilowii group was also higher than that in the untreated group but the difference was not statistically significant (P>0.05). All the expression levels, including those of vWF, HIF-1α, HIF-1β and VEGF, in the salidroside group were higher than those in the untreated group while lower than those in the Radix et Rhizoma Rhodiolae Kirilowii group.
Conclusion

Radix et Rhizoma Rhodiolae Kirilowii may promote angiogenesis in myocardium of rats with AMI through elevating the expressions of HIF-1α, HIF-1β, and VEGF. Salidroside may be one of the effective components in Radix et Rhizoma Rhodiolae Kirilowii, which increases the expressions of HIF-1α, HIF-1β and VEGF during ischemia or hypoxia.

Key words: Radix et Rhizoma Rhodiolae Kirilowii, Salidroside, Hypoxia-inducible factor 1, Vascular endothelial growth factors, Acute myocardial infarction, Rats

"

Target gene Primer and probe Size of product (bp)
HIF-1α Forward: 5'-GTG TGT GTG AAT TAT GTT GTA AGT GGT ATT-3' 125
Reverse: 5'-TTA GTG AAC AGC TGG GTC ATT TTC-3'
Probe: FAM-CAG CAC GAC TTG ATT TTC TCC CTT CAA CAA-TAMRA
HIF-1β Forward: 5'-CTG TTT CCA TGA ATA GAC TGA GCT TTT-3' 91
Reverse: 5'-ACT ACC ACA AAG TGA GGC TCT CCT T-3'
Probe: FAM-AGG AAC AGA TGC AGG AAT GGA CTT GGC-TAMRA
VEGF Forward: 5'-GGA TCT TGG ACA AAC AAA TGC TT-3' (reverse complement) 83
Reverse: 5'-CGC AAG AAA TCC CGG TTT AA-3'
Probe: FAM-CTG AAC AAG GCT CAC AGT GAA CGC TCC-TAMRA
β-actin Forward: 5'-GTC AGG TCA TCA CTA TCG GCA AT-3' 147
Reverse: 5'-AGA GGT CTT TAC GGA TGT CAA CGT-3'
Probe: FAM-CCT TCC TTC CTG GGT ATG GAA TCC TGT GP-TAMRA

"

Group n Expression of vWF protein
Infarct border zone Non-infarct zone
Untreated 3 2.032±0.220▲▲ 0.616±0.075
Radix et Rhizoma Rhodiolae Kirilowii 4 4.410±0.485*△▲▲ 1.077±0.186*
Salidroside 4 3.217±0.292*▲▲ 0.854±0.147*

Figure 1

Expressions of vWF protein at infarct border zone or non-infarct zone in three groups detected by immunohistochemical SP method (Light microscopy, ×200) A: Untreated group, infarct border zone; B: Radix et Rhizoma Rhodiolae Kirilowii group, infarct border zone; C: Salidroside group, infarct border zone; D: Untreated group, non-infarct zone; E: Radix et Rhizoma Rhodiolae Kirilowii group, non-infarct zone; F: Salidroside group, non-infarct zone."

"

Group n HIF-1α/106 β-actin HIF-1β/106 β-actin VEGF/106 β-actin
Untreated 7 0.572 (0.372, 0.584) 0.254 (0.225, 0.265) 0.202 (0.136, 0.207)
Radix et Rhizoma Rhodiolae Kirilowii 8 10.200 (3.507, 10.575)**△△ 0.989 (0.770, 0.995)** 1.460 (0.853, 2.802)**
Salidroside 7 2.150 (1.100, 2.370)** 0.691 (0.563, 0.699)** 0.262 (0.255, 1.680)**

"

Group n HIF-1α/β-actin HIF-1β/β-actin VEGF/β-actin
Untreated 7 0.520 (0.006, 1.023) 0.474 (0.431, 1.093) 1.327 (1.051, 1.654)
Radix et Rhizoma Rhodiolae Kirilowii 8 2.024 (1.554, 2.128)** 1.014 (0.852, 1.660) 2.196 (1.747, 2.438)**
Salidroside 7 1.844 (1.496, 1.942)** 0.841 (0.394, 1.001) 1.416 (1.409, 1.541)

Figure 2

Expressions of HIF-1α, HIF-1β and VEGF proteins in three groups detected by Western blotting analysis 1: Untreated group; 2: Radix et Rhizoma Rhodiolae Kirilowii group; 3: Salidroside group."

[1] Syed IS, Sanborn TA, Rosengart TK . Therapeutic angiogenesis: a biologic bypass[J]. Cardiology, 2004,101(1-3):131-143
doi: 10.1159/000075994
[2] Ahn A, Frishman WH, Gutwein A, Passeri J, Nelson M . Therapeutic angiogenesis: a new treatment approach for ischemic heart disease - part Ⅰ[J]. Cardiol Rev, 2008,16(4):163-171
doi: 10.1097/CRD.0b013e3181620e3b
[3] Ahn A, Frishman WH, Gutwein A, Passeri J, Nelson M . Therapeutic angiogenesis: a new treatment approach for ischemic heart disease - Part Ⅱ[J]. Cardiol Rev, 2008,16(5):219-229
doi: 10.1097/CRD.0b013e3181620e50
[4] Wang S, Zheng Z, Weng Y, Yu Y, Zhang D, Fan W, Dai R, Hu Z . Angiogenesis and anti-angiogenesis activity of Chinese medicinal herbal extracts[J]. Life Sci, 2004,74(20):2467-2478
doi: 10.1016/j.lfs.2003.03.005
[5] Ke Q, Costa M . Hypoxia-inducible factor-1(HIF-1)[J]. Mol Pharmacol, 2006,70(5):1469-1480
doi: 10.1124/mol.106.027029
[6] Li J, Fan WH, Ao H, Huang AM, Luo XP, Shi HM, Li Y . Effect of Rhodiola on expressions of Flt-1, KDR and Tie-2 in rats with ischemic myocardium[J]. Zhongguo Zhong Xi Yi Jie He Za Zhi, 2005,25(5):445-448
李剑, 范维琥, 敖红, 黄爱民, 罗心平, 施海明, 李勇 . 中药红景天对大鼠缺血心肌Flt-1、KDR及Tie-2表达的影响[J]. 中国中西医结合杂志, 2005,25(5):445-448
[7] Zhao HY, Guan HH, Zhong XY, Chen YX . Making rat myocardial infarction model by thoracotomy and ligating coronary artery[J]. Guo Wai Yi Xue Nei Ke Xue Fen Ce, 2005,32(12):540-542
赵洪云, 管慧红, 钟雪云, 陈运贤 . 开胸冠状动脉结扎法制作大鼠心肌梗死模型[J]. 国外医学内科学分册, 2005,32(12):540-542
[8] Teng JR, Xiong JP, Xiao C, Wang X . Progress in modern pharmacology of Rhodiola[J]. Zhongguo Zhong Yi Ji Chu Yi Xue Za Zhi, 2006,12(4):319-320
滕静如, 熊佳鹏, 肖诚, 王昕 . 红景天的现代药理学研究进展[J]. 中国中医基础医学杂志, 2006,12(4):319-320
[9] Yuan Y, Zhang L, Li YF . Active components and pharmacological action of integripetal Rhodiola herb[J]. Shi Pin Yu Yao Pin, 2007,9(5):54-57
袁瑜, 张良, 李玉锋 . 红景天活性成分及药理作用[J]. 食品与药品, 2007,9(5):54-57
[10] Zanetta L, Marcus SG, Vasile J, Dobryansky M, Cohen H, Eng K, Shamamian P, Mignatti P . Expression of von Willebrand factor, an endothelial cell marker, is up-regulated by angiogenesis factors: a potential method for objective assessment of tumor angiogenesis[J]. Int J Cancer, 2000,85(2):281-288
doi: 10.1002/(ISSN)1097-0215
[11] Lee JW, Bae SH, Jeong JW, Kim SH, Kim KW . Hypoxia-inducible factor(HIF-1)α: its protein stability and biological functions[J]. Exp Mol Med, 2004,36(1):1-12
doi: 10.1038/emm.2004.1
[12] Déry MA, Michaud MD, Richard DE . Hypoxia-inducible factor 1: regulation by hypoxic and non-hypoxic activators[J]. Int J Biochem Cell Biol, 2005,37(3):535-540
doi: 10.1016/j.biocel.2004.08.012
[13] Kaur B, Khwaja FW, Severson EA, Matheny SL, Brat DJ, Van Meir EG . Hypoxia and the hypoxia-inducible-factor pathway in glioma growth and angiogenesis[J]. Neuro Oncol, 2005,7(2):134-153
doi: 10.1215/S1152851704001115
[14] Ferrara N . Vascular endothelial growth factor: basic science and clinical progress[J]. Endocr Rev, 2004,25(4):581-611
doi: 10.1210/er.2003-0027
[15] Josko J, Mazurek M .Transcription factors having impact on vascular endothelial growth factor (VEGF) gene expression in angiogenesis[J].Med Sci Monit, 2004, 10(4):RA89-RA98
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