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1.150001 哈尔滨, 哈尔滨工业大学化工与化学学院食品科学与工程系
2.150040 哈尔滨, 黑龙江中医药大学药物安全评价中心
[单毓娟,E-mail:yujuan72@163.com SHAN Yujuan, E-mail: yujuan72@163.com
[李宝龙,E-mail:lbl73@163.com LI Baolong, E-mail: lbl73@163.com
收稿:2018-12-05,
修回:2019-02-12,
纸质出版:2019-06-30
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田思聪, 雷鹏, 孙瑶, 等. 莱菔硫烷下调DGAT2和ACAT1表达抑制肝脂肪变的研究[J]. 第三军医大学学报, 2019,41(12):1102-1109.
Sicong TIAN, Peng LEI, Yao SUN, et al. Sulforaphane inhibits hepatic steatosis in rats by down-regulating DGAT2 and ACAT1 expression[J]. Journal of Third Military Medical University, 2019, 41(12): 1102-1109.
田思聪, 雷鹏, 孙瑶, 等. 莱菔硫烷下调DGAT2和ACAT1表达抑制肝脂肪变的研究[J]. 第三军医大学学报, 2019,41(12):1102-1109. DOI: 10.16016/j.1000-5404.201812039.
Sicong TIAN, Peng LEI, Yao SUN, et al. Sulforaphane inhibits hepatic steatosis in rats by down-regulating DGAT2 and ACAT1 expression[J]. Journal of Third Military Medical University, 2019, 41(12): 1102-1109. DOI: 10.16016/j.1000-5404.201812039.
目的
2
研究莱菔硫烷(sulforaphane,SFN)对脂肪滴和脂滴外周蛋白的影响,阐明莱菔硫烷抑制高脂摄入引起的非酒精性脂肪肝的作用机制。
方法
2
建立高脂膳食诱导大鼠肝脏脂肪变性模型,用莱菔硫烷干预。根据体质量将60只雄性
Wistar大鼠按随机数表法分为6组(
n
=10):正常食物组、高脂饲料组、高脂饲料+高剂量莱菔硫烷(20 mg/kg)处理组、高脂饲料+中剂量莱菔硫烷(10 mg/kg)处理组、高脂饲料+低剂量莱菔硫烷(5 mg/kg)处理组和高脂饲料+阳性药物(30 mg/kg)组。检测各组大鼠肝组织中甘油三酯和总胆固醇的含量,采用油红O染色观察大鼠肝脏内脂滴形态;Western blot检测大鼠肝脏中甘油三酯和胆固醇的关键合成酶DGAT2和ACAT1蛋白的表达;免疫组化和实时定量PCR检测脂滴外周蛋白PLIN1、PLIN2、PLIN3和PLIN5的表达。
结果
2
莱菔硫烷能够减轻高脂饲料引起的大鼠体质量的增加,降低大鼠肝脏内甘油三酯和总胆固醇的含量,减少脂肪滴积累,缩小脂肪滴体积。各剂量莱菔硫烷均显著下调大鼠肝脏中DGAT2和ACAT1蛋白的表达(
P
<
0.01)。高剂量莱菔硫烷组大鼠肝组织中PLIN2、PLIN5 mRNA和蛋白表达明显下调(
P
<
0.01,
P
<
0.05)。
结论
2
莱菔硫烷可以通过降低大鼠肝组织中DGAT2、ACAT1的表达以及脂滴外周蛋白PLIN2、PLIN5的表达,抑制脂滴的生成。
Objective
2
To study the effects of sulforaphane (SFN) on the deposition of lipid droplets and the expression of their peripheral proteins in the liver and elucidate the mechanism by which SFN inhibits non-alcoholic fatty liver caused by high-fat diet.
Methods
2
Sixty male Wistar rats were randomized into 6 equal groups (
n
=10)
including
a
normal food group
a
high-fat diet group
3 high-fat diet groups treated with high (20 mg/kg)
moderate (10 mg/kg) and low (5 mg/kg) doses of SFN
and
a
high-fat diet group treated with
a
positive drug (30 mg/kg). Triglyceride and total cholesterol contents were examined and the deposition of lipid droplets in the liver was detected with oil red
O
staining in all the rats. The protein expression of DGAT2 and ACAT1 (the key synthases of triglyceride and cholesterol
respectively) in the liver tissues were detected with Western blotting; immunohistochemistry and real-time PCR were performed to examine the expression of the PAT proteins (PLIN1
PLIN2
PLIN3 and PLIN5) at both the protein and mRNA levels in the liver.
Results
2
SFN treatment obviously reduced high-fat diet-induced bodyweight g
ain in the rats
lowered the levels of triglyceride and total cholesterol
lessened lipid droplet deposition in the liver and reduced the volume of the lipid droplets. Treatment with SFN at all the 3 doses significantly down-regulated the expression of ACAT1 and DGAT2 in the liver of the rats (
P
<
0.01). SFN at the high doses significantly down-regulated the expression of PLIN2 and PLIN5 in liver tissue at both the mRNA and protein levels (
P
<
0.01
P
<
0.05).
Conclusion
2
SFN can inhibit the formation of lipid droplets by reducing the expressions of DGAT2
ACAT1
PLIN2 and PLIN5 in the liver of rats.
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