Effect of Shuangyu Tiaozhi Decoction on NPC1L1 and ABCG8 in Intestine of Hyperlipemic Model Rats

Ruo-qi LI; Jing-jing SHI; Hai-fei LU; Lu YU; Feng-xia ZHANG

doi:10.13422/j.cnki.syfjx.20191402

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Effect of Shuangyu Tiaozhi Decoction on NPC1L1 and ABCG8 in Intestine of Hyperlipemic Model Rats

Pharmacology | 更新时间：2021-02-09

- Effect of Shuangyu Tiaozhi Decoction on NPC1L1 and ABCG8 in Intestine of Hyperlipemic Model Rats
- Chinese Journal of Experimental Traditional Medical Formulae Vol. 25, Issue 14, Pages: 77-83(2019)
- 作者机构：
  
  1.山东中医药大学，济南　 250355；
  2.山东中医药大学　附属医院，济南　 250011
- 作者简介：
- 基金信息：
- DOI：10.13422/j.cnki.syfjx.20191402
  CLC： R2-0; R22; R285.5; R289
- Received：28 December 2018，
  
  Published Online：04 April 2019，
  
  Published：20 July 2019
- 稿件说明：
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Ruo-qi LI, Jing-jing SHI, Hai-fei LU, et al. Effect of Shuangyu Tiaozhi Decoction on NPC1L1 and ABCG8 in Intestine of Hyperlipemic Model Rats[J]. Chinese journal of experimental traditional medical formulae, 2019, 25(14): 77-83.
DOI：

Ruo-qi LI, Jing-jing SHI, Hai-fei LU, et al. Effect of Shuangyu Tiaozhi Decoction on NPC1L1 and ABCG8 in Intestine of Hyperlipemic Model Rats[J]. Chinese journal of experimental traditional medical formulae, 2019, 25(14): 77-83. DOI： 10.13422/j.cnki.syfjx.20191402.

摘要

目的：

观察高脂血症模型大鼠小肠组织中尼曼-匹克C1型类蛋白1(NPC1L1)及三磷酸腺苷结合盒转运体G8(ABCG8)的表达水平，探讨双蓣调脂汤对高脂血症的治疗机制。

方法：

选取40只雄性SD大鼠，随机选取8只大鼠为正常组，其余32只建立高脂血症大鼠模型，造模成功后随机分为模型组(等量生理盐水)，双蓣调脂汤高、低剂量组(15.6，7.8 g·kg

－1

)，辛伐他汀组(4 mg·kg

－1

)，共4组，每组8只，灌胃给药8周。生化法和酶法测定各组大鼠血清总胆固醇(TC)，甘油三酯(TG)及肝脏总胆固醇(TTC)，游离胆固醇(FTC)的含量；采用苏木素-伊红(HE)染色光镜下观察肝组织形态学的变化；运用逆转录-聚合酶链式反应(RT-PCR)和蛋白免疫印迹法(Western blot)检测大鼠小肠组织NPC1L1，ABCG8及肝X受体

(LXR-

)表达水平；免疫组化法测定ABCG8蛋白表达的水平。

结果：

高脂血症大鼠模型复制成功。与正常组比较，模型组血脂水平明显增高，肝脏脂肪变性明显，NPC1L1，LXR-

及ABCG8表达水平明显升高(

0.05，

0.01)；与模型组比较，双蓣调脂汤组血脂水平明显下降，NPC1L1和LXR-

的表达明显下调，ABCG8的表达明显上调，呈现一定的剂量依赖性(

0.05，

0.01)。免疫组化法检测结果显示，与正常组比较，模型组小肠中ABCG8蛋白表达水平升高(

0.01)；与模型组比较，各给药组ABCG8蛋白表达水平显著上调(

0.05，

0.01)，其中双蓣调脂汤高剂量组效果最为显著(

0.05)。

结论：

双蓣调脂汤通过减少胆固醇的吸收来降低高脂血症模型大鼠的血脂水平，其机制可能与下调NPC1L1的表达，上调ABCG8的表达有关。

Abstract

Objective:

To observe the expression levels of niemann-pick C1-like 1 (NPC1L1) and adenosine triphosphate-binding cassette transporters G8 (ABCG8) in intestine of hyperlipidemic model rats

in order to investigate the therapeutic mechanism of Shuangyu Tiaozhi decoction on hyperlipidemia.

Method:

A total of 40 SD rats were selected

including 8 for normal control group. The remaining 32 rats were used to establish hyperlipemic model. After modeling

the rats were randomly divided into the model group (equivalent normal saline)

the high and low-dose Shuangyu Tiaozhi groups (15.6

7.8 g·kg

-1

)

and the Simvastatin group (4 mg·kg

-1

)

with 8 in each group. They were given drugs by gavage for 8 weeks. The levels of total cholesterol (TC)

triglyceride (TG) in serum and total cholesterol (TTC)

free cholesterol (FTC) in liver of rats in each group were determined by biochemical and enzymatic methods. The morphological changes of liver were observed by hematoxylin-eosin (HE) staining

and the levels of expressions of NPC1L1

ABCG8 and liver X receptor-

(LXR-

) in intestine were detected by Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) and Western blot. The expression of ABCG8 protein was determined by immunohistochemistry.

Result:

After successful replication of the hyperlipidemia model

the blood lipid level was abnormally increased

and the liver steatosis became obvious in the model group compared with the normal control group. The expression levels of NPC1L1

LXR-

and ABCG8 increased significantly (

0.05

0.01). Compared with the model group

the blood lipid levels were significantly reduced in the Shuangyu Tiaozhi decoction group. The expressions of NPC1L1 and LXR-

were significantly down-regulated

but ABCG8 was obviously up-regulated in a dose-dependent manner (

0.05

0.01). The results of immunohistochemistry indicated that the protein expression of ABCG8 in intestine of the model group increased significantly (

0.01). Compared with the model group

the expression of ABCG8 in each drug-administered groups increased obviously (

0.05

0.01)

especially in high-dose Shuangyu Tiaozhi group (

0.05).

Conclusion:

Shuangyu Tiaozhi decoction can reduce the blood lipid level of hyperlipemic rat model by reducing the absorption of cholesterol. Its mechanism may be correlated with the down-regulation of NPC1L1 expression and the up-regulation of ABCG8 expression.

关键词

Keywords

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