Effect of Ginseng Radix et Rhizoma, Notoginseng Radix et Rhizoma and Chuanxiong Rhizoma Extracts on Expression of α-SMA and Runx2 Protein After High Glucose-induced Vascular aging in Mice
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Effect of Ginseng Radix et Rhizoma, Notoginseng Radix et Rhizoma and Chuanxiong Rhizoma Extracts on Expression of α-SMA and Runx2 Protein After High Glucose-induced Vascular aging in Mice
Chinese Journal of Experimental Traditional Medical FormulaeVol. 26, Issue 8, Pages: 21-29(2020)
Yan-hong HU, Jing-yi FANG, Xue WANG, et al. Effect of Ginseng Radix et Rhizoma, Notoginseng Radix et Rhizoma and Chuanxiong Rhizoma Extracts on Expression of α-SMA and Runx2 Protein After High Glucose-induced Vascular aging in Mice[J]. Chinese journal of experimental traditional medical formulae, 2020, 26(8): 21-29.
DOI:
Yan-hong HU, Jing-yi FANG, Xue WANG, et al. Effect of Ginseng Radix et Rhizoma, Notoginseng Radix et Rhizoma and Chuanxiong Rhizoma Extracts on Expression of α-SMA and Runx2 Protein After High Glucose-induced Vascular aging in Mice[J]. Chinese journal of experimental traditional medical formulae, 2020, 26(8): 21-29. DOI: 10.13422/j.cnki.syfjx.20200702.
Effect of Ginseng Radix et Rhizoma, Notoginseng Radix et Rhizoma and Chuanxiong Rhizoma Extracts on Expression of α-SMA and Runx2 Protein After High Glucose-induced Vascular aging in Mice
To investigate the effects of Ginseng Radix et Rhizoma
Notoginseng Radix et Rhizoma and Chuanxiong Rhizoma extracts (GNC) on the protein expression of
α
-smooth muscle actin (
α
-SMA) and runt-related transcription factor2(Runx2) after high glucose-induced vascular aging in mice
and elucidate the protective mechanism of GNC in delaying vascular aging.
Method:
2
Totally 130 male C57BL/6 mice were randomly divided into normal control group and high glucose group. The mice in high glucose group were intraperitoneally injected with streptozotocin (STZ). After successful modeling
the mice received high-fat diet for 7 months
and then they were randomly divided into model group
GNC low-dose and high-dose groups (0.819
1.638 g·kg
-1
)
and metformin group (150 mg·kg
-1
). The drug was given by intragastric administration once a day for 9 weeks. Seven days before tissues collection
a new batch of 4-week-old male C57BL/6 mice were purchased and fed normally for 1 week as a youth group. The general condition of the mice was observed. Morphological changes of the common carotid artery in mice were determined by hematoxylin-eosin (HE) staining and transmission electron microscopy (TEM). Masson trichromatic staining was used to observe the fibrosis of common carotid artery in mice. The expression levels of matrix metalloproteinases-2 (MMP-2)
cyclin-dependent kinase inhibitor 2A (p16)
cyclic-dependent kinase inhibitor 1A (p21)
α
-SMA and Runx2 in the common carotid arteries of mice were detected by immunohistochemistry.
Result:
2
The results of HE
TEM and Masson showed that there was almost no change in the inimal and adventitial thickness
ultrastructure and relative contents of collagen and elastic fibers in the common carotid arteries of mice between the youth group and normal control group. As compared with the normal control group
the intima of the common carotid artery in the model group was not smooth
the endothelial cells were almost completely detached
the cytoplasm was lysed
the inner elastic membrane became thinner
fractured
or even detached
and the proliferating collagen fibers sneaked into the tunica media. The hyperplasia of tunica media and tunica adventitia was obvious and disordered (
P
<
0.01). The vascular smooth muscle cells showed deformations
protuberances
bifurcations
and even fragmentation
and focal necrosis was observed. There were significantly more vacuoles
lysosomes
and obvious autophagy vesicles. The relative content of collagen and elastic fibers in vascular walls increased significantly (
P
<
0.01). Compared with the model group
the above situation was relieved in each administration group (
P
<
0.01). The results of immunohistochemistry showed that high glucose induced high expression of MMP-2
p16
p21 and Runx2 in the common carotid arteries(
P
<
0.01)
low expression of
α
-SMA(
P
<
0.01)
and the protein expression tended to be normal after drug intervention(
P
<
0.05
P
<
0.01).
Conclusion:
2
High glucose can induce the aging of common carotid artery in mice and change the expression of
α
-SMA and Runx2 proteins. The Ginseng Radix et Rhizoma
Notoginseng Radix et Rhizoma and Chuanxiong Rhizoma extracts can delay vascular aging by regulating the protein expression of
M F NEVES , A R CUNHA , M R CUNHA , et al . The role of renin-angiotensin-aldosterone system and its new components in arterial stiffness and vascular aging [J]. High Blood Press Cardiovasc Prev , 2018 , 16 ( 61 ): 1 - 9 .
A CHAUHAN , M A AL , G SPIEGEL , et al . Splenectomy protects aged mice from injury after experimental stroke [J]. Neurobiol Aging , 2018 , 61 ( 1 ): 102 - 111 .
R J HODES , F Sierra , S N Austad , et al . Disease drivers of aging [J]. Ann Ny Acad Sci , 2016 , 1386 ( 1 ): 45 .
R A HAYWARD , P D REAVEN , W L WIITALA , et al . Follow-up of glycemic control and cardiovascular outcomes in type 2 diabetes [J]. New Engl J Med , 2015 , 372 ( 23 ): 2197 - 2206 .
M M XU , H Y DENG , H H LI . MicroRNA-27a regulates angiotensin Ⅱ-induced vascular smooth muscle cell proliferation and migration by targeting α -smooth muscle-actin in vitro [J]. Biochem Bioph Res Co , 2019 , 509 ( 4 ): 973 - 977 .
F BARTOLI-LEONARD , F L WILKINSON , A SCHIRO , et al . Suppression of SIRT1 in diabetic conditions induces osteogenic differentiation of human vascular smooth muscle cells via RUNX2 signalling [J]. Sci Rep-UK , 2019 , 9 ( 1 ): 878 .
G CARRICK-RANSON , F G SPINALE , P S BHELLA , et al . Plasma matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs and aging and lifelong exercise adaptations in ventricular and arterial stiffness [J]. Exp Gerontol , 2019 , 123 : 36 - 44 .
G JIA , A R AROOR , C JIA , et al . Endothelial cell senescence in aging-related vascular dysfunction [J]. BBA-Mol Basis Dis , 2019 , 1865 ( 7 ): 1802 - 1809 .
G SUN , H SONG , S WU . miR19a promotes vascular smooth muscle cell proliferation, migration and invasion through regulation of Ras homolog family member B [J]. Int J Mol Med , 2019 , 44 ( 6 ): 1991 - 2002 .
M WANG , R E MONTICONE , K R MCGRAW . Proinflammatory arterial stiffness syndrome: a signature of large arterial aging [J]. J Vasc Res , 2018 , 55 ( 4 ): 210 - 223 .
L ZHANG , C WEI , Y RUAN , et al . Serum containing Buyang Huanwu decoction prevents age-associated migration and invasion of human vascular smooth muscle cells by up regulating SIRT1 expression [J]. Biosci Trends , 2018 , 12 ( 3 ): 282 - 290 .
F WILLECKE , B RUPPRECHT , M C GISSLER , et al . Tumor necrosis factor receptor-associated factor 5 promotes arterial neointima formation through smooth muscle cell proliferation [J]. J Vasc Res , 2019 , undefined : 1 - 12 .
A F PRADO , L PERNOMIAN , A AZEVEDO , et al . Matrix metalloproteinase-2-induced epidermal growth factor receptor transactivation impairs redox balance in vascular smooth muscle cells and facilitates vascular contraction [J]. Redox Biol , 2018 , 18 : 181 - 190 .
K E WEBB , A M HENNEY , S ANGLIN , et al . Expression of matrix metalloproteinases and their inhibitor TIMP-1 in the rat carotid artery after balloon injury [J]. Arterioscl Throm Vas , 1997 , 17 ( 9 ): 1837 - 1844 .
L ZHANG , C WEI , Y RUAN , et al . Serum containing Buyang Huanwu decoction prevents age-associated migration and invasion of human vascular smooth muscle cells by up regulating SIRT1 expression [J]. Biosci Trends , 2018 , 12 ( 3 ): 282 - 290 .
F BRINGOLD , M SERRANO . Tumor suppressors and oncogenes in cellular senescence [J]. Exp Gerontol , 2000 , 35 ( 3 ): 317 - 329 .
J DUAN , Z ZHANG , T TONG . Senescence delay of human diploid fibroblast induced by anti-sense p16INK4a expression [J]. J Biol Chem , 2001 , 276 ( 51 ): 48325 - 48331 .
G XIAO , D JIANG , C GE , et al . Cooperative interactions between activating transcription factor 4 and Runx2/Cbfa1 stimulate osteoblast-specific osteocalcin gene expression [J]. J Biol Chem , 2005 , 280 ( 35 ): 30689 - 30696 .
R T FRANCESCHI , G XIAO . Regulation of the osteoblast-specific transcription factor, Runx2: responsiveness to multiple signal transduction pathways [J]. J Cell Biochem , 2003 , 88 ( 3 ): 446 - 454 .
I AL-HUSEINI , N ASHIDA , T KIMURA . Deletion of I κ B-Kinase β in smooth muscle cells induces vascular calcification through β -Catenin-Runt-related transcription factor 2 signaling [J]. J Am Heart Assoc , 2018 , 7 ( 1 ): e007405 .
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Related Author
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Cheng-kui XIU
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Jia-li WANG
Yi-qing LIU
Yan LEI
Yan-hong HU
Related Institution
School of Pharmacy, Jiangxi University of Chinese Medicine
Tianjin Medical University Chu Hsien-I Memorial Hospital, Tianjin Institute of Endocrinology,NHC Key Laboratory of Hormones and Development, Tianjin Institute of Endocrinology
Beijing University of Chinese Medicine
Minzu University of China
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