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人参皂苷Rg1对D-半乳糖所致小鼠心肌损伤的保护作用
Protective effects of ginsenoside Rg1 on cardiac muscle of aging mice induced by D-galactose
- 第三军医大学学报 2021年43卷第11期 页码：1074-1079
- 作者机构：
400016 重庆，重庆医科大学干细胞与组织工程研究室，基础医学院组织学与胚胎学教研室
- 作者简介：
[王亚平, E-mail：ypwangcq@aliyun.com WANG Yaping, E-mail: ypwangcq@aliyun.com
- 基金信息：国家自然科学基金面上项目(81673748);国家自然科学基金面上项目(81873103)
DOI：10.16016/j.1000-5404.202012240
中图分类号： R285.5;R542.2;R589.1收稿：2020-12-30，
修回：2021-02-07，
纸质出版：2021-06-15
- 稿件说明：
移动端阅览
李赓, 汪子铃, 候吉颖, 等. 人参皂苷Rg1对D-半乳糖所致小鼠心肌损伤的保护作用[J]. 第三军医大学学报, 2021,43(11):1074-1079.
Geng LI, Ziling WANG, Jiying HOU, et al. Protective effects of ginsenoside Rg1 on cardiac muscle of aging mice induced by D-galactose[J]. Journal of Third Military Medical University, 2021, 43(11): 1074-1079.
李赓, 汪子铃, 候吉颖, 等. 人参皂苷Rg1对D-半乳糖所致小鼠心肌损伤的保护作用[J]. 第三军医大学学报, 2021,43(11):1074-1079. DOI： 10.16016/j.1000-5404.202012240.
Geng LI, Ziling WANG, Jiying HOU, et al. Protective effects of ginsenoside Rg1 on cardiac muscle of aging mice induced by D-galactose[J]. Journal of Third Military Medical University, 2021, 43(11): 1074-1079. DOI： 10.16016/j.1000-5404.202012240.
摘要
目的
2
探讨人参皂苷Rg1对D-半乳糖(D-galactose
D-gal)所致小鼠心肌损伤的保护作用和初步机制。
方法
2
C57BL/6J小鼠按抽签法随机分为4组，每组10只。D-gal损伤模型组：给小鼠腹腔注射D-gal(200 mg·kg
-1
·d
-1
×42 d)；Rg1干预模型组：按D-gal损伤模型组小鼠处理，从建模第16天起腹腔注射Rg1(40 mg·kg
-1
·d
-1
×26 d)；对照组：腹腔注射等量生理盐水42 d；Rg1对照组：按对照组处理小鼠16 d，再腹腔注射Rg1(剂量同Rg1干预模型组)。各组处理完成后第2天，取心脏测定脏器指数；石蜡切片，HE染色观察心肌组织病理学，透射电镜观察心肌纤维超微结构；酶标比色法检测心肌组织匀浆中谷草转氨酶(AST)、乳酸脱氢酶(LDH)、总超氧化物歧化酶(T-SOD)、过氧化氢酶(CAT)活性和丙二醛(MDA)表达量；Western blot检测心肌组织中Nrf2、Keap1、HO-1蛋白表达。
结果
2
D-gal损伤模型组小鼠心脏指数明显升高(
P
<
0.01)；心肌纤维间胶原纤维沉积量增加；肌原纤维束排列紊乱，心肌纤维直径显著增大，线粒体形态异常伴有肿胀；心肌组织的AST、LDH活力显著升高，T-SOD、CAT活性显著降低，MDA表达量显著升高(
P
<
0.05)；Nrf2、HO-1蛋白表达量显著降低(
P
<
0.05)，Keap1蛋白表达量无显著变化。Rg1干预模型组小鼠心脏指数明显降低(
P
<
0.01)；胶原纤维沉积量减少，肌原纤维束排列较为整齐
心肌纤维直径与正常对照组相比无统计学差异，线粒体形态基本正常，无明显肿胀；AST、LDH活力显著降低，T-SOD、CAT活性显著升高，MDA表达量显著降低(
P
<
0.05)；Nrf2、HO-1蛋白表达量显著升高，Keap1蛋白表达量显著降低(
P
<
0.01)。
结论
2
Rg1能有效拮抗D-gal对小鼠心肌组织结构和超微结构的损伤，其机制可能与抑制氧化应激和上调Nrf2抗氧化信号通路有关。
Abstract
Objective
2
To investigate the protective effects and primary mechanism of ginsenoside Rg1 on cardiac muscle of aging mice induced by D-galactose (D-gal).
Methods
2
C57BL/6 J mice were randomly divided into normal control
model
Rg1 intervention and negative control groups
with 10 animals in each group. D-gal (200 mg/kg) was injected intraperitoneally to the mice for 42 d to establish the model group
and the mice of the Rg1 intervention group was given 40 mg/kg Rg1 per day for 26 d intraperitoneally from the 16th day of model establishment. The mice of the normal control group were given same amount of normal saline for 42 d
and those of the negative control group were treated with normal saline after model establishment. On the 2nd day after treatment
the hearts were taken to measure the organ index. HE staining and transmission electron microscopy were performed to observe the morphology and micro-structures of the heart tissue from each group. The activities of aspartate aminotransferase (AST)
lactate dehydrogenase (LDH)
total superoxide dismutase (T-SOD)
catalase (CAT) and contents of malondialdehyde (MDA) in the myocardial tissue homogenate were tested by enzyme-labeled colorimetry; The expression levels of Nrf2
Keap1 and HO-1 in the heart tissue were detected by Western blotting.
Results
2
Compared with the control group
the model group had significantly increased heart index (
P
<
0.01); larger amount of deposited collagen fibers between myocardial fibers
disordered myofibril bundles
thicker myocardial fibers
and abnormally swollen mitochondria; enhanced AST and LDH activities
declined T-SOD and CAT activities
and increased MDA content (
P
<
0.05); remarkably down-regulation of Nrf2 and HO-1 (
P
<
0.05)
and no changed Keap1 level. While in the Rg1 intervention group
all the above phenomena were greatly improved after the intervention
with obviously decreased heart index (
P
<
0.01)
not notable morphological changes with normal control mice
reversed AST
LDH
T-SOD and CAT activities and MDA contents(
P
<
0.05)
and elevated protein levels of Nrf2 and HO-1
and decreased level of Keap1 (
P
<
0.01).
Conclusion
2
Rg1 effectively alleviates the damage of D-gal to the morphology and ultrastructure of mouse myocardium
and its mechanism may be related to the inhibition of oxidative stress and the up-regulation of the Nrf2 antioxidant signal pathway.
关键词
Keywords
references
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