叶酸联合维生素B12对高脂饮食大鼠脂质代谢的影响

摘要/Abstract

摘要：

目的了解叶酸联合维生素B₁₂对高脂饮食大鼠脂质代谢的影响，为脂质代谢相关疾病的防治提供参考。方法将30只雄性SD大鼠按体质量随机分为2组，10只作为空白对照组喂饲常规饲料，另外20只喂饲高脂饲料28天后，按血清总胆固醇与三酰甘油水平随机平均分为2组：叶酸联合维生素B₁₂干预组（叶酸剂量1.00 mg/kg+维生素B₁₂剂量0.06 mg/kg）和高脂饮食组。采用灌胃方式干预，干预期40天，高脂饮食组与空白对照组给予等量生理盐水，并继续喂饲对应饲料。干预第0、20、40天，测定血清三酰甘油、总胆固醇、低密度脂蛋白胆固醇（low density lipoprotein cholesterol，LDL-C）和高密度脂蛋白胆固醇（high density lipoprotein cholesterol，HDL-C）水平，记录动物体质量。实验末期，测定肝组织匀浆三酰甘油和总胆固醇水平，ELISA法测定血清脂联素、抵抗素及白细胞介素（interleukin，IL）6水平，qPCR法测定肝组织中脂质代谢酶胆固醇7α-羟化酶（cholesterol 7α-hydroxylase，CYP7A1）、3-羟基3-甲基戊二酰辅酶A还原酶（3-hydroxy-3-methyl glutaryl coenzyme A reductase，HMGCR）、脂肪酸合酶（fatty acid synthase，FAS）和乙酰辅酶A羧化酶（acetylcoenzyme A carboxylase，ACC）的mRNA表达水平。结果与空白对照组比较，干预第0、20、40天时，高脂饮食组血清总胆固醇、三酰甘油和LDL-C水平升高，差异均有统计学意义（均P<0.05）；与高脂饮食组比较，干预第20、40天，叶酸联合维生素B₁₂干预组血清总胆固醇、三酰甘油及LDL-C水平均降低，差异均有统计学意义（均P<0.05）。干预40天后，高脂饮食组肝脏总胆固醇、三酰甘油水平显著高于空白对照组（均P<0.05），血清脂联素水平显著低于空白对照组，血清抵抗素与IL-6水平显著高于空白对照组（均P<0.05），肝脏 CYP7A1 mRNA表达水平显著低于空白对照组，HMGCR、FAS及ACC mRNA表达水平显著高于空白对照组（均P<0.05）；与高脂饮食组相比，叶酸联合维生素B₁₂干预组肝脏三酰甘油、总胆固醇水平显著降低（均P<0.05），血清脂联素显著升高，抵抗素与IL-6水平显著降低（均P<0.05），肝脏HMGCR和FAS mRNA表达水平显著降低（均P<0.05）。结论叶酸联合维生素B₁₂能够影响高脂饮食大鼠脂质代谢，其作用机制可能与其下调关键脂质代谢酶HMGCR、FAS的表达，影响脂肪细胞因子脂联素、抵抗素与IL-6的分泌有关。

关键词: 叶酸, 维生素B₁₂, 联合作用, 高脂饮食, 脂质代谢, 大鼠

Abstract:

Objective To explore the effects of folic acid combined with vitamin B₁₂ on lipid metabolism in rats with high-fat diet，and to provide a reference for the prevention and treatment of lipid metabolism-related diseases. Methods Totally 30 SD rats were divided into 2 groups randomly by body weight，10 SD male rats were fed by conventional diet as control group. After 28 days of high fat diet，the other 20 rats were allotted into 2 groups equally depending on total cholesterol and triglyceride，including folic acid combined with vitamin B₁₂ group（folic acid dose 1.00 mg/kg and vitamin B₁₂ dose 0.06 mg/kg） and high-fat diet group. All rats were oral gavaged daily for 40 days. The high-fat diet group and the control group were given an equivalent amount of 0.9% saline solution. The levels of total cholesterol，triglyceride，low density lipoprotein cholesterol（LDL-C） and high density lipoprotein cholesterol（HDL-C） in the serum were measured on 0th day，20th day and 40th day of intervention，and the body weight of rats were recorded. At the end of intervention，the levels of total cholesterol and triglyceride in liver tissue homogenate were detected，and the level of adiponectin，resistin and interleukin（IL）-6 were measured using ELISA method. The qPCR method were used to determine the hepatic mRNA expression of lipid metabolism enzymes including cholesterol 7α-hydroxylase（CYP7A1），3-hydroxy-3-methyl glutaryl coenzyme A reductase（HMGCR），fatty acid synthase（FAS） and acetylcoenzyme A carboxylase（ACC）. Results At 0th，20th and 40th day of intervention，the levels of serum total cholesterol，triglyceride and LDL-C in high-fat diet group were higher than those in the control group，and the differences were statistically significant（all P<0.05）. At 20th day and 40th day of intervention，the levels of serum total cholesterol，triglyceride and LDL-C in folic acid combined with vitamin B₁₂ group were lower than those in the high fat diet group，and the differences were statistically significant（all P<0.05）. At 40th day of intervention，the levels of hepatic total cholesterol and triglyceride in high fat diet group were higher than those in the control group，the level of serum adiponectin in high fat diet group was lower than that in the control group，the level of serum resistin and IL-6 in high fat diet group were higher than those in the control group，the hepatic mRNA expression of CYP7A1 in high fat diet group was lower than that in the control group，the hepatic mRNA expression of HMGCR，FAS and ACC in high fat diet group were higher than those in the control group，and the differences were statistically significant（all P<0.05）. The levels of hepatic total cholesterol and triglyceride in folic acid combined with vitamin B₁₂ group was significantly lower than that in high fat group，the levels of serum adiponectin in folic acid combined with vitamin B₁₂ group was significantly higher than that in high fat group，and the levels of serum resistin and IL-6 in folic acid combined with vitamin B₁₂ group were significantly lower than those in the high-fat group（all P<0.05），and the hepatic mRNA expression of HMGCR and FAS were significantly lower than those in the high-fat group（all P<0.05）. Conclusion Folic acid combined with vitamin B₁₂ can improve the lipid metabolism in rats with high-fat diet. The possible molecular mechanism may be related to inhibiting the expression of key lipid metabolic enzymes including FAS and ACC，and regulating the secretion of adipokines such as adiponectin，resistin and IL-6.

Key words: Folic acid, Vitamin B₁₂, Combined effect, High-fat diet, Lipid metabolism, Rats

中图分类号:

R-332

张大龙, 周殿明, 张露, 李敏, 岳文博, 钱智勇. 叶酸联合维生素B₁₂对高脂饮食大鼠脂质代谢的影响. [J]职业与健康, 2026, 42(4): 459-464.

ZHANG Dalong, ZHOU Dianming, ZHANG Lu, LI Min, YUE Wenbo, QIAN Zhiyong. Effects of folic acid combined with vitamin B₁₂ on lipid metabolism in rats with high-fat diet. [J]OCCUPATION AND HEALTH, 2026, 42(4): 459-464.

图/表 8

参考文献 21

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组别	只数	第0 天	第20天	第40天
叶酸联合维生素B₁₂ 干预组	10	409.4±19.3	478.6±31.7	536.6±41.1
高脂饮食组	10	402.4±14.2	481.0±21.2	540.9±28.3
空白对照组	10	391.2±25.4	464.0±34.0	500.6±36.5
F值		1.773	0.985	2.321
P		>0.05	>0.05	>0.05

组别	只数	第0 天	第20天	第40天
叶酸联合维生素B₁₂ 干预组	10	409.4±19.3	478.6±31.7	536.6±41.1
高脂饮食组	10	402.4±14.2	481.0±21.2	540.9±28.3
空白对照组	10	391.2±25.4	464.0±34.0	500.6±36.5
F值		1.773	0.985	2.321
P		>0.05	>0.05	>0.05

组别	只数	第0天	第20天	第40天
叶酸联合维生素B₁₂ 干预组	10	2.24±0.40^a	2.39±0.44^ab	2.08±0.57^b
高脂饮食组	10	2.29±0.54^a	2.78±0.36^a	2.71±0.43^a
空白对照组	10	1.71±0.42	1.95±0.40	2.06±0.48
F值		5.002	10.767	5.553
P		<0.05	<0.01	<0.05

组别	只数	第0天	第20天	第40天
叶酸联合维生素B₁₂ 干预组	10	2.24±0.40^a	2.39±0.44^ab	2.08±0.57^b
高脂饮食组	10	2.29±0.54^a	2.78±0.36^a	2.71±0.43^a
空白对照组	10	1.71±0.42	1.95±0.40	2.06±0.48
F值		5.002	10.767	5.553
P		<0.05	<0.01	<0.05

组别	只数	第0天	第20天	第40天
叶酸联合维生素B₁₂ 干预组	10	0.80±0.16^a	0.59±0.19^b	0.59±0.23^b
高脂饮食组	10	0.81±0.13^a	0.80±0.18^a	0.84±0.33^a
空白对照组	10	0.59±0.10	0.54±0.17	0.54±0.18
F值		8.886	5.889	4.105
P		<0.01	<0.01	<0.05

叶酸联合维生素B₁₂对高脂饮食大鼠脂质代谢的影响

Effects of folic acid combined with vitamin B₁₂ on lipid metabolism in rats with high-fat diet

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Metrics

组别	只数	第0天	第20天	第40天
叶酸联合维生素B₁₂ 干预组	10	0.58±0.11^a	0.60±0.20^b	0.43±0.13^b
高脂饮食组	10	0.57±0.16^a	0.80±0.18^a	0.66±0.10^a
空白对照组	10	0.33±0.10	0.47±0.14	0.40±0.11
F值		13.461	8.696	15.718
P		<0.01	<0.01	<0.01

组别	只数	第0天	第20天	第40天
叶酸联合维生素B₁₂ 干预组	10	0.87±0.15	1.16±0.20	1.49±0.47
高脂饮食组	10	0.89±0.27	1.03±0.34	1.53±0.36
空白对照组	10	0.97±0.20	1.28±0.32	1.75±0.37
F值		0.623	1.824	1.215
P		>0.05	>0.05	>0.05

组别	只数	总胆固醇	三酰甘油
叶酸联合维生素B₁₂ 干预组	10	1.64±0.46^ab	5.63±0.99^ab
高脂饮食组	10	2.31±0.35^a	6.60±0.50^a
空白对照组	10	1.28±0.31	2.74±0.53
F值		18.540	79.804
P值		<0.01	<0.01

组别	只数	脂联素（mg/L）	抵抗素（pg/L）	IL-6（ng/L）
叶酸联合维生素B₁₂ 干预组	10	127.65±5.95^ab	203.25±8.48^ab	20.83±1.77^ab
高脂饮食组	10	116.10±12.98^a	257.87±37.27^a	27.71±1.07^a
空白对照组	10	131.90±6.49	174.55±34.17	16.73±4.67
F值		8.162	20.443	35.373
P值		<0.01	<0.01	<0.01

组别	只数	CYP7A1	HMGCR	FAS	ACC
叶酸联合维生素B₁₂ 干预组	5	0.59±0.21^a	2.41±0.56^b	3.22±1.14^ab	2.17±0.93^a
高脂饮食组	5	0.41±0.26^a	6.40±1.87^a	8.44±3.14^a	2.49±1.04^a
空白对照组	5	1.05±0.12	1.00±0.07	1.05±0.20	1.05±0.22
F值		12.668	30.932	19.293	4.329
P		<0.01	<0.01	<0.01	<0.05

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