糖尿病相关非酒精性脂肪性肝病和肝纤维化的治疗靶点、新型药物及给药系统
Therapeutic targets, novel drugs, and delivery systems for diabetes associated NAFLD and liver fibrosis.
作者信息
Kumar Virender, Xin Xiaofei, Ma Jingyi, Tan Chalet, Osna Natalia, Mahato Ram I
机构信息
Department of Pharmaceutical Sciences, University of Nebraska Medical Center, Omaha, NE 68198, USA.
Department of Pharmaceutics and Drug Delivery, University of Mississippi, University, MS 38677, USA.
出版信息
Adv Drug Deliv Rev. 2021 Sep;176:113888. doi: 10.1016/j.addr.2021.113888. Epub 2021 Jul 24.
Type 2 diabetes mellitus (T2DM) associated non-alcoholic fatty liver disease (NAFLD) is the fourth-leading cause of death. Hyperglycemia induces various complications, including nephropathy, cirrhosis and eventually hepatocellular carcinoma (HCC). There are several etiological factors leading to liver disease development, which involve insulin resistance and oxidative stress. Free fatty acid (FFA) accumulation in the liver exerts oxidative and endoplasmic reticulum (ER) stresses. Hepatocyte injury induces release of inflammatory cytokines from Kupffer cells (KCs), which are responsible for activating hepatic stellate cells (HSCs). In this review, we will discuss various molecular targets for treating chronic liver diseases, including homeostasis of FFA, lipid metabolism, and decrease in hepatocyte apoptosis, role of growth factors, and regulation of epithelial-to-mesenchymal transition (EMT) and HSC activation. This review will also critically assess different strategies to enhance drug delivery to different cell types. Targeting nanocarriers to specific liver cell types have the potential to increase efficacy and suppress off-target effects.
2型糖尿病（T2DM）相关的非酒精性脂肪性肝病（NAFLD）是第四大死因。高血糖会引发多种并发症，包括肾病、肝硬化，最终导致肝细胞癌（HCC）。有几种导致肝病发展的病因，其中涉及胰岛素抵抗和氧化应激。肝脏中游离脂肪酸（FFA）的积累会产生氧化应激和内质网（ER）应激。肝细胞损伤会诱导库普弗细胞（KCs）释放炎性细胞因子，这些细胞因子负责激活肝星状细胞（HSCs）。在本综述中，我们将讨论治疗慢性肝病的各种分子靶点，包括FFA的稳态、脂质代谢、肝细胞凋亡的减少、生长因子的作用以及上皮-间质转化（EMT）和HSC激活的调节。本综述还将批判性地评估增强药物向不同细胞类型递送的不同策略。将纳米载体靶向特定肝细胞类型有可能提高疗效并抑制脱靶效应。
Zotero 插件