葛仙米对高脂血症小鼠氧化应激的保护作用

刘银路; 杨丽涛; 毕萃萃; 魏芬芬; 张波

doi:10.13386/j.issn1002-0306.2020090140

Protective Effect of Nostoc sphaeroids Kütz on Oxidative Stress in Hyperlipidemic Mice

Beijing Key Laboratory of Bioactive Substance and Functional Food, Research Institute for Science and Technology of Functional Foods, Beijing Union University, Beijing100191, China

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Corresponding author:
ZHANG Bo: 张波（1962−），女，博士，教授，研究方向：生物活性物质的功能与毒理，Email：zhangbo_wl@buu.edu.cn

葛仙米对高脂血症小鼠氧化应激的保护作用

北京联合大学功能食品科学技术研究院, 生物活性物质与功能食品北京市重点实验室，北京 100191

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中图分类号: TS201.4
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出版历程
- 收稿日期: 2020-09-14
- 网络出版日期: 2021-05-13
- 刊出日期: 2021-07-14

摘要

Abstract: Most health problems associated with aging, such as wrinkles, heart disease and Alzheimer's disease were caused by excessive oxidative stress in the body. Hyperlipidemia caused by high-fat diet(HFD) would lead to lipid metabolism disorder, oxidative stress and so on. The purpose of this study was to investigate the protective effect of Nostoc sphaeroids Kütz(NSK) on diet-induced hyperlipidemia in mice. In the experiment, six-week-old C57BL/6j male mice were fed with high-fat diet(HFD) for 4 weeks, and then fed with high-fat diet supplemented with different doses of NSK for 6 weeks. Results showed that: High-fat diet could lead to hyperlipidemia and obvious dyslipidemia in mice. The addition of NSK to high-fat diet decreased serum triglyceride(TG), serum total cholesterol(TC), low density lipid cholesterol(LDL-C), while high density lipid cholesterol(HDL-C) increased significantly(P<0.05). It could also significantly reduce the liver index and the enzyme activities of alanine transaminase(ALT) and aspartate transaminase(AST). Through the results of this experiment, it was found that the level of malondialdehyde (MDA) in the liver tissue of 2.5% and 7.5% NSK group decreased, while total antioxidant capacity(T-AOC), hepatic superoxide dismutase(SOD) and glutathione(GSH) increased, and the difference was statistically significant(P<0.05). Furthermore, the expression of LDLR,CYP7a1 and LXR-α in liver tissue of mice supplemented with NSK in HFD significantly increased(P<0.05). In conclusion, NSK hadlipid-lowering effect on HFD-fed mice and it might be related to increase the antioxidant activity and gene expression of LDLR and CYP7a1.
- Nostoc sphaeroids Kütz /
- hyperlipidemia /
- mice /
- oxidative stress
摘要: 大多数与衰老相关的健康问题，如皱纹、心脏病和阿尔茨海默氏症，都是由体内过度的氧化应激引起的。高脂饮食（HFD）引起的高脂血症会导致机体脂质代谢紊乱、氧化应激等，为探究葛仙米对饮食诱导的小鼠高脂血症的保护作用，实验选用6周龄C57BL/6J雄性小鼠，先喂饲高脂饲料（HFD）4周，然后在高脂饲料中添加不同剂量的葛仙米饲喂6周。结果表明，高脂饮食可导致小鼠高脂血症和明显的血脂异常。高脂饮食中添加葛仙米可降低血清甘油三酯（TG）、总胆固醇（TC）、低密度脂蛋白胆固醇（LDL-C），升高高密度脂蛋白胆固醇（HDL-C），能显著降低肝指数和丙氨酸氨基转移酶（ALT）、天冬氨酸氨基转移酶（AST）活性。2.5%和7.5%葛仙米组小鼠肝组织丙二醛（MDA）含量显著降低，总抗氧化能力（T-AOC）、肝组织超氧化物歧化酶（SOD）和谷胱甘肽（GSH）含量显著升高（P<0.05）。此外，葛仙米还能显著增加肝组织低密度脂蛋白受体、CYP7a1和LXR-α的表达（P<0.05）。综上，葛仙米对高脂饲料喂养的小鼠具有降脂作用，其机制可能与提高LDLR和CYP7a1的抗氧化活性及基因表达有关。
- 葛仙米 /
- 高脂血症 /
- 小鼠 /
- 氧化应激

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Figure 1. Body weight and food utilization rate

Notes: (a). Body weight during modeling; (b). Body weight during NSK intervation; (c). Food utilization rate during modeling; (d). Food utilization rate during NSK intervation ( $\mathrm{F}\mathrm{o}\mathrm{o}\mathrm{d}\;\mathrm{ }\mathrm{u}\mathrm{t}\mathrm{i}\mathrm{l}\mathrm{i}\mathrm{z}\mathrm{a}\mathrm{t}\mathrm{i}\mathrm{o}\mathrm{n}\mathrm{ }\;\mathrm{r}\mathrm{a}\mathrm{t}\mathrm{e}\left(\text{%}\right)=\dfrac{{\rm{Food}}\; {\rm{intake}}\; {\rm{of}}\; {\rm{mice}}\left({\rm{g}}\right)}{{\rm{Mouse}}\; {\rm{weight}}\; {\rm{gain}}\left({\rm{g}}\right)}\times 100$ ). Bars marked with different letters represent statistically significant (P<0.05), whereas bars labeled with the same letter indicate no statistically significant difference between the groups (P>0.05).

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Figure 2. Effects of NSK on lipid levels in serum

Notes: (a).Lipid levels at week 1~4 , (b). Lipid levels at week 5~10; Values represent mean ± SEM; n=10 in each group. Bars marked with different letters represent statistically significant (P<0.05), whereas bars labeled with the same letter indicate no statistically significant difference between the groups (P>0.05).

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Figure 3. Effects of NSK on liver injury in mice with high-fat die

Notes: (a). Typical liver morphological images, C: Control, M: HFD, L:NSK (2.5%), H: NSK (7.5%); (b). ALT in serum; (c). AST in serum. Bars marked with different letters represent statistically significant (P<0.05), whereas bars labeled with the same letter indicate no statistically significant difference between the groups (P>0.05).

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Figure 4. Effect of NSK on lipid peroxidation and antioxidants in liver

Notes: (a).The concentration of T-AOC in liver; (b). The enzyme activity of SOD in liver; (c). The concentration of GSH in liver; (d). The concentration of MDA in liver; Values represent mean±SEM, n=10 in each group;Bars marked with different letters represent statistically significant (P<0.05), whereas bars labeled with the same letter indicate no statistically significant difference between the groups (P>0.05).

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Figure 5. Effect of NSK on liver mRNA expression in mice

Notes: Bars marked with different letters represent statistically significant (P<0.05), whereas bars labeled with the same letter indicate no statistically significant difference between the groups (P>0.05).

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Table 1 Composition of assay diets

Ingredient (g)	Control diet	HFD	NSK (2.5%)	NSK (7.5%)
Cornstarch	465.7	235.7	233.2	228.2
Casein	140	110	110	110
Dextrinized cornstarch	155	155	155	155
Sucrose	100	100	100	100
Soybean oil	40	40	40	40
Choline bitartrate	2.5	2.5	2.5	2.5
Fiber¹	50	50	50	50
Mineral mix²	35	35	35	35
Vitamin mix³	10	10	10	10
L-Cysteine	1.8	1.8	1.8	1.8
Lard	0	150	150	150
Cholesterol	0	10	10	10
yolk	0	100	100	100
NSK powder	0	0	25	75
Note:1: Solka-Floc cellulose. 2: AIN-93 mineral mix. 3: AIN-93 vitamin.

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Table 2 Primer pairs used for the real-time quantitative PCR analysis

Genbank ID	Gene Name	Primer Sequence (5' to 3')
NM_007393.3	β-actin	GTGACGTTGACATCCGTAAAGA
NM_007393.3	β-actin	GTAACAGTCCGCCTAGAAGCAC
NM_001252658.1	LDLR	ATTCAGTCCCAGGCAGCGTATC
NM_001252658.1	LDLR	TTCTTGATCTTGGCGGGTGTTC
NM_001278601.1	CYP7a1	GGGGATTGCTGTGGTAGTGAG
NM_001278601.1	CYP7a1	CAGGGAGTTTGTGATGAAGTGG
NM_001177730.1	LXR-α	CCCACGACCCACTGATGTTC
NM_001177730.1	LXR-α	CACAAAGGACACGGTGAAACA

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Table 3 Effect of Nostoc sphaeroides Kütz on liver index of mice

Dose	animals	body weight	liver weight	Liver index(%)
Control	10	24.73±0.88^c	0.86±0.27^c	3.45±0.94^d
HFD	10	28.73±1.08a	1.63±0.39^a	5.53±1.02^a
2.5%NSK	10	27.05±0.86^ab	1.53±0.42^a	5.16±1.37^ab
7.5%NSK	10	26.26±0.61^b	1.25±0.34^b	4.66±0.96^bc
Notes: Values represent mean ± SEM; n=10 in each group. Superscript letters represent statistically significant differences (P<0.05). Instances of the same letter between groups indicate that no statistically significant difference was found (P>0.05).

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