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延胡索乙素可预防金黄仓鼠(Mesocricetus auratus)高脂饮食诱导的血脂异常。

Tetrahydropalmatine Prevents High-Fat Diet-Induced Hyperlipidemia in Golden Hamsters (Mesocricetus Auratus).

机构信息

Department of Pharmacy, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China (mainland).

The Second Central Laboratory, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China (mainland).

出版信息

Med Sci Monit. 2018 Sep 18;24:6564-6572. doi: 10.12659/MSM.910578.

Abstract

BACKGROUND Hyperlipidemia is a major cause of atherosclerotic cardiovascular disease. Tetrahydropalmatine (THP) can exhibit hepatoprotective, anti-arrhythmic, and anti-inflammatory activities. The mechanism of THP on the hyperlipidemia remains unknown; therefore, the present study explored the role of THP in hyperlipidemia. MATERIAL AND METHODS We established an animal model of hyperlipidemia by high-fat diet (HFD) feeding. Blood samples were obtained for determination of serum cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-c), high-density lipoprotein cholesterol (HDL-c), pro-inflammatory cytokines, and CYP7A1 expression. Histology was performed and inflammation was detected in the liver using hematoxylin-eosin (HE) staining and enzyme-linked immunosorbent assay (ELISA), respectively. The mRNA and protein levels of TLR4 and TRAF-6 were determined by quantitative real-time PCR (qPCR) and Western blot, respectively. RESULTS THP suppressed hepatic lipid accumulation and reduced serum levels of TC, TG, LDL-c, and HDL-c in HFD-fed golden hamsters. THP increased cholesterol 7 a-hydroxylase (CYP7A1) expression and prevented inflammation by the limited reduction in interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) expressions in serum and liver. THP slightly increased the ratio of the body/liver weight. THP inhibited the mRNA and protein levels of Toll-like receptor 4 (TLR4) and TNF-receptor associated factor-6 (TRAF-6). CONCLUSIONS These results suggest that THP attenuates hyperlipidemia by multiple effects, including hepatoprotective and anti-inflammatory effects. Moreover, THP also suppressed the expressions of TLR4 and TRAF-6 in golden hamsters.

摘要

背景

高脂血症是动脉粥样硬化性心血管疾病的主要病因。延胡索乙素(THP)具有保肝、抗心律失常和抗炎作用。THP 对高脂血症的作用机制尚不清楚;因此,本研究探讨了 THP 在高脂血症中的作用。

材料和方法

我们通过高脂饮食(HFD)喂养建立了高脂血症动物模型。采集血液样本,测定血清胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDL-c)、高密度脂蛋白胆固醇(HDL-c)、促炎细胞因子和 CYP7A1 表达。分别采用苏木精-伊红(HE)染色和酶联免疫吸附试验(ELISA)检测肝脏组织学和炎症。通过定量实时 PCR(qPCR)和 Western blot 分别测定 TLR4 和 TRAF-6 的 mRNA 和蛋白水平。

结果

THP 抑制 HFD 喂养金黄地鼠肝脂质蓄积,降低血清 TC、TG、LDL-c 和 HDL-c 水平。THP 通过降低血清和肝脏中白细胞介素 6(IL-6)和肿瘤坏死因子-α(TNF-α)的表达,增加胆固醇 7α-羟化酶(CYP7A1)的表达,减轻炎症。THP 略微增加了体重/肝重比。THP 抑制 TLR4 和 TNF 受体相关因子 6(TRAF-6)的 mRNA 和蛋白水平。

结论

这些结果表明,THP 通过多种作用减轻高脂血症,包括保肝和抗炎作用。此外,THP 还抑制了金黄地鼠 TLR4 和 TRAF-6 的表达。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7683/6157085/398b416615d2/medscimonit-24-6564-g001.jpg

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