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Advances in ultrasound-targeted microbubble-mediated gene therapy for liver fibrosis

机译:超声靶向微泡介导的肝纤维化基因治疗研究进展

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Hepatic fibrosis develops as a wound-healing scar in response to acute and chronic liver inflammation and can lead to cirrhosis in patients with chronic hepatitis B and C. The condition arises due to increased synthesis and reduced degradation of extracellular matrix (ECM) and is a common pathological sequela of chronic liver disease. Excessive deposition of ECM in the liver causes liver dysfunction, ascites, and eventually upper gastrointestinal bleeding as well as a series of complications. However, fibrosis can be reversed before developing into cirrhosis and has thus been the subject of extensive researches particularly at the gene level. Currently, therapeutic genes are imported into the damaged liver to delay or prevent the development of liver fibrosis by regulating the expression of exogenous genes. One technique of gene delivery uses ultrasound targeting of microbubbles combined with therapeutic genes where the time and intensity of the ultrasound can control the release process. Ultrasound irradiation of microbubbles in the vicinity of cells changes the permeability of the cell membrane by its cavitation effect and enhances gene transfection. In this paper, recent progress in the field is reviewed with emphasis on the following aspects: the types of ultrasound microbubbles, the construction of an ultrasound-mediated gene delivery system, the mechanism of ultrasound microbubble-mediated gene transfer and the application of ultrasound microbubbles in the treatment of liver fibrosis.
机译:肝纤维化是对急性和慢性肝炎的反应,可作为伤口愈合的疤痕发展,并可能导致慢性乙型和丙型肝炎患者肝硬化。该病因合成增加和细胞外基质(ECM)降解降低而出现,是一种慢性肝病的常见病理后遗症。 ECM在肝脏中过多沉积会导致肝功能障碍,腹水,并最终导致上消化道出血以及一系列并发症。然而,纤维化在发展为肝硬化之前可以逆转,因此已经成为广泛研究的主题,尤其是在基因水平上。目前,通过调节外源基因的表达,将治疗基因导入受损的肝脏中,以延迟或预防肝纤维化的发展。基因递送的一种技术是将微泡的超声靶向与治疗性基因结合,其中超声的时间和强度可以控制释放过程。细胞附近微泡的超声照射通过其空化作用改变了细胞膜的通透性,并增强了基因转染。本文综述了该领域的最新进展,重点包括以下方面:超声微泡的类型,超声介导的基因传递系统的构建,超声微泡介导的基因转移机制以及超声微泡的应用。在治疗肝纤维化。

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