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人参-三七-川芎提取物对高糖诱导小鼠血管老化后
α -SMA和Runx2蛋白表达的影响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- 中国实验方剂学杂志 2020年26卷第8期 页码：21-29
- 作者机构：
1.中国中医科学院 医学实验中心，北京市中医药防治重大疾病基础研究重点实验室，北京 100700
2.广东药科大学 中医药研究院，广东省代谢性疾病中西医结合研究中心，广州 510006
- 作者简介：
[第一作者] 胡艳红，在读博士，从事中西医结合心血管病研究，Tel：010-64089525，E-mail：huyanhong3737@163.com
*雷燕，博士，首席研究员，从事中西医结合心血管病研究，Tel：010-64089525，E-mail：13651217893@163.com
- 基金信息：国家自然科学基金面上项目(81673822);中国中医科学院自主选题项目(ZZ2018014;ZZ2017011)
DOI：10.13422/j.cnki.syfjx.20200702
中图分类号： R2-0; R22; R285.5收稿日期：2019-10-12，
网络出版日期：2019-12-18，
纸质出版日期：2020-04-20
- 稿件说明：
移动端阅览
胡艳红, 方靖漪, 王雪, 等. 人参-三七-川芎提取物对高糖诱导小鼠血管老化后
α -SMA和Runx2蛋白表达的影响[J]. 中国实验方剂学杂志, 2020,26(8):21-29.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.胡艳红, 方靖漪, 王雪, 等. 人参-三七-川芎提取物对高糖诱导小鼠血管老化后
α -SMA和Runx2蛋白表达的影响[J]. 中国实验方剂学杂志, 2020,26(8):21-29. DOI： 10.13422/j.cnki.syfjx.20200702.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.
摘要
目的：
2
为了研究人参-三七-川芎提取物(GNC)对高糖诱导小鼠血管老化后
α
-平滑肌肌动蛋白(
α
-SMA)和runt相关转录因子2(Runx2)蛋白表达的调控作用，阐明GNC延缓血管老化的保护作用机制。
方法：
2
C57BL/6小鼠，130只，雄性，随机分为正常组和高糖组。高糖组腹腔注射链脲佐菌素(STZ)，造模成功后，喂食高脂饲料7个月，之后再次随机分为模型组，GNC低、高剂量组(0.819，1.638 g·kg
-1
)及二甲双胍组(150 mg·kg
-1
)。灌胃给药，每天1次，连续9周。取材前7 d，新购一批4周龄雄性C57BL/6小鼠正常喂养1周，为青年组。观察小鼠一般情况，实验结束后分别用苏木素-伊红(HE)染色结合透射电镜(TEM)观察小鼠颈总动脉形态学变化，马松(Masson)染色观察小鼠颈总动脉纤维化，免疫组化检测小鼠颈总动脉中基质金属蛋白酶-2(MMP-2)，周期蛋白依赖激酶抑制因子2A(p16)，周期依赖性蛋白激酶抑制因子1A(p21)，
α
-SMA与Runx2蛋白表达。
结果：
2
HE，TEM，Masson 3个实验结果显示：与青年组比较，正常组小鼠颈总动脉中内外膜厚度、超微结构和血管壁中胶原和弹性纤维的相对含量几乎无变化；与正常组比较，模型组小鼠颈总动脉内膜不光滑，内皮细胞几乎完全脱落，胞质裂解，内弹性膜变薄、断裂、甚至脱离，可见增生的胶原纤维潜入中膜，中外膜增生明显且排列紊乱(
P
<
0.01)，血管平滑肌细胞变形、突起、分叉增多、甚至碎裂，并可见局灶性坏死，细胞内空泡和溶酶体等大量增多，并可见明显的自噬泡。血管壁中外膜胶原和弹性纤维的相对含量增加明显(
P
<
0.01)；与模型组比较，各给药组以上病理情况均有所改善(
P
<
0.01)。免疫组化结果显示：与正常组比较，模型组小鼠颈总动脉MMP-2，p16，p21，Runx2高表达(
P
<
0.01)，
α
-SMA低表达(
P
<
0.01)；与模型组比较，各给药组各蛋白表达趋于正常(
P
<
0.05，
P
<
0.01)。
结论：
2
高糖能够诱导小鼠颈总动脉血管老化，改变
α
-SMA，Runx2蛋白表达。GNC可通过调节
α
-SMA，Runx2蛋白表达，延缓血管老化。
Abstract
Objective:
2
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
α
-SMA and Runx2.
关键词
Keywords
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