a Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology , Nanfang Hospital, Southern Medical University , Guangzhou , China.
b Nanfang Hospital, Southern Medical University , Guangzhou , China.
Artif Cells Nanomed Biotechnol. 2018;46(sup2):217-228. doi: 10.1080/21691401.2018.1453830. Epub 2018 Mar 21.
Non-alcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases worldwide, and precision therapeutic will be a benefit for the NAFLD regression. In this study, we observed low microRNA 146 b (miR-146 b) expression in NAFLD mice model induced by methionine-choline-deficient diet (MCD) compared with control group. Furthermore, miR-146b mice induced MCD exhibited severe liver steatosis and hepatitis. A bio-distribution study showed that novel Lactosylated PDMAEMA nanoparticles effectively targeted hepatocytes Lac-PDMAEMA. We coupled miR-146b mimic with Lac-PDMAEMA and then were administrated to NAFLD mice model, which could obviously alleviate the hepatic steatosis. Lac-PDMAEMA effectively delivered miR-146b mimic to hepatocytes with a ∼8-fold upregulation of miR-146b mimic targeting MyD88 and IRAK1, and in turn suppressed the expression of PPARγ. Meanwhile, TNF-α and IL-6 mRNA levels were decreased after administration of Lac-PDMAEMA/miR-146b mimic. So, we made a conclusion that targeted delivering miR-146b mimic to the hepatocytes by, coupling Lac-PDMAEMA nanoparticles could effectively alleviate the hepatic steatosis in NAFLD mice, which maybe bring a new and effective way to intervene and therapy the NAFLD.
非酒精性脂肪性肝病（NAFLD）是全球最常见的慢性肝病之一，精准治疗将有益于 NAFLD 的消退。在本研究中，我们观察到，与对照组相比，蛋氨酸-胆碱缺乏饮食（MCD）诱导的 NAFLD 小鼠模型中 miR-146b 的表达水平较低。此外，诱导 MCD 的 miR-146b 小鼠表现出严重的肝脂肪变性和肝炎。一项生物分布研究表明，新型乳糖化 PDMAEMA 纳米粒可有效靶向肝细胞 Lac-PDMAEMA。我们将 miR-146b 模拟物与 Lac-PDMAEMA 偶联，然后给予 NAFLD 小鼠模型，可明显减轻肝脂肪变性。Lac-PDMAEMA 可有效将 miR-146b 模拟物递送至肝细胞，从而使 miR-146b 模拟物靶向 MyD88 和 IRAK1 的表达增加约 8 倍，并进而抑制 PPARγ 的表达。同时，给予 Lac-PDMAEMA/miR-146b 模拟物后，TNF-α 和 IL-6 的 mRNA 水平降低。因此，我们得出结论，通过偶联 Lac-PDMAEMA 纳米粒靶向递送至肝细胞的 miR-146b 模拟物，可有效减轻 NAFLD 小鼠的肝脂肪变性，为干预和治疗 NAFLD 带来了新的有效途径。
