Effect of Linggui Zhugan Tang on Hepatic FXR/FGF15/SHP Pathway in ob/ob Mice with Leptin-deficient

LIU Li-ping; LI Ran; ZHANG Li-de; ZHANG Lan-chuan; XU Shuang

doi:10.13422/j.cnki.syfjx.20182218

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Effect of Linggui Zhugan Tang on Hepatic FXR/FGF15/SHP Pathway in ob/ob Mice with Leptin-deficient

更新时间：2024-09-23

- Effect of Linggui Zhugan Tang on Hepatic FXR/FGF15/SHP Pathway in ob/ob Mice with Leptin-deficient
- Chinese Journal of Experimental Traditional Medical Formulae Vol. 24, Issue 22, Pages: 107-111(2018)
- 作者机构：
- 作者简介：
- 基金信息：
- DOI：10.13422/j.cnki.syfjx.20182218
  CLC： R285.5
- Published：2018
- 稿件说明：
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LIU Li-ping, LI Ran, ZHANG Li-de, et al. Effect of Linggui Zhugan Tang on Hepatic FXR/FGF15/SHP Pathway in ob/ob Mice with Leptin-deficient[J]. Chinese journal of experimental traditional medical formulae, 2018, 24(22): 107-111.
DOI：

LIU Li-ping, LI Ran, ZHANG Li-de, et al. Effect of Linggui Zhugan Tang on Hepatic FXR/FGF15/SHP Pathway in ob/ob Mice with Leptin-deficient[J]. Chinese journal of experimental traditional medical formulae, 2018, 24(22): 107-111. DOI： 10.13422/j.cnki.syfjx.20182218.

摘要

目的：观察苓桂术甘汤对瘦素基因缺陷小鼠肝脏的影响，探讨其保护作用机制是否与其干预肝法尼醇X受体（FXR）/成纤维细胞生长因子15（FGF15）/小异源二聚体伴侣（SHP）途径有关。方法：将雌性C57小鼠和ob/ob小鼠随机分为正常组，模型组，苓桂术甘汤高、低剂量组（23.1，7.7 g·kg-1），阳性药组（立普妥，0.002 6 g·kg-1），每组各8只。治疗4周后处死小鼠，取小鼠肝脏组织，称量小鼠体质量和肝脏质量，计算肝脏指数；苏木素-伊红（HE）染色和油红O染色观察肝脏组织形态和脂质沉积情况，免疫荧光染色检测肝脏组织法尼醇X受体（farnesoid X receptor，FXR）和蛋白免疫印迹法（Western blot）检测成纤维细胞生长因子15（FGF15）和酪氨酸磷酸酶（SHP）蛋白表达。结果：与正常组比较，模型组体质量和肝脏指数显著增高（P<0.01），肝脏脂质沉积严重，肝脏组织FXR，FGF15和SHP蛋白表达下调（P<0.01）；与模型组比较，苓桂术甘汤组小鼠体质量和肝脏指数降低（P<0.05，P<0.01），肝脏脂质沉积减少，上调肝脏组织FXR，FGF15和SHP蛋白表达（P<0.05，P<0.01）。结论：苓桂术甘汤能够抗瘦素基因缺陷模型小鼠的肝损伤，其作用机制可能与其干预肝FXR-FGF15-SHP途径有关。

Abstract

Objective:To investigate the effect of Linggui Zhugan Tang on the hepatic steatosis in leptin-deficient mice

in order to explore the possible mechanism of Linggui Zhugan Tang on farnesoid X receptor(FXR)fibroblast growth factor 15(FGF15)-small heterodimer partner(SHP) pathway. Method:The mice were divided into five groups:normal group

model group

high-dose Linggui Zhugan Tang group(23.1 g·kg-1)

low-dose Linggui Zhugan Tang group(7.7 g·kg-1)

and positive drug group(0.002 6 g·kg-1). After 4 weeks of treatment

the weight of body was recorded

and the liver organ coefficient was calculated. The effect of Linggui Zhugan Tang on hepatic steatosis was investigated by htoxylin eosin(HE) and oil red O staining. The protein expressions of FXR

FGF15

and SHP in the liver were detected by immunofluorescence staining and Western blot. Result:Compared with normal group

the body weight and liver index were significantly increased

with serious hepatic steatosis

while the protein expression level of FXR

FGF15 and SHP were significantly lower in ob/ob mice(P<0.01). Compared with model group

the body weight and liver index were declined

whereas the protein expressions of FXR

FGF15

and SHP were significantly up-regulated after treatment(P<0.05

P<0.01). Conclusion:Linggui Zhugan Tang could improve the hepatic steatosis in ob/ob mice

which may be related to its effect on FXR/FGF15/SHP pathway.

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