低相对分子质量壳聚糖-乙酰半胱氨酸偶合物肾脏靶向递送系统的研究

发布时间：2018-05-16 05:36

本文选题：乙酰半胱氨酸 + 低相对分子质量壳聚糖　；参考：《中国药学杂志》2017年08期

【摘要】：目的合成低相对分子质量壳聚糖-乙酰半胱氨酸(LMWC-NAC)偶合物,并且评价其在急性肾损伤模型动物体内的肾脏靶向性及疗效。方法以碳二亚胺/N-羟基琥珀酰亚胺为缩合剂,将乙酰半胱氨酸通过酰胺反应嫁接到低相对分子质量壳聚糖上,并且采用核磁共振进行结构确证。在体外细胞实验中,考察LMWC-NAC偶合物被肾小管上皮细胞(HK-2)摄取的能力以及参与摄取过程的megalin受体。此外,用荧光材料吲哚菁绿标记LMWC-NAC偶合物,并对其在裸鼠体内的分布情况进行考察。腹腔注射脂多糖(20 mg·kg~(-1))构建急性肾损伤动物模型,给药72 h后检测各组小鼠的血肌酐、血尿素氮、炎症因子(TNF-α和IL-1β)、氧化应激(MDA),HE染色观察肾脏组织的病理学改变。结果通过酰胺反应得到LMWC-NAC偶合物,体外实验证实其通过megalin受体的介导被HK-2细胞摄取,而体内分布实验表明,LMWC-NAC偶合物在肾脏组织具有较好的分布,AKI小鼠尾静脉注射LMWC-NAC偶合物后,血清尿素氮和肌酐得到显著改善(P0.01),炎症因子和氧化应激指标也显著下降(P0.01),减轻肾脏病理损伤。结论 LMWC-NAC偶合物对肾脏具有较好的靶向性和改善其功能的能力,表明其可用于急性肾损伤的治疗。
[Abstract]:Objective to synthesize a low molecular weight chitosan-acetylcysteine (LMWC-NAC) coupling compound and evaluate its renal targeting and efficacy in acute renal injury model. Methods acetylcysteine was grafted onto low molecular weight chitosan with carbdiimide / N- hydroxysuccinimide as the reagents and its structure was confirmed by NMR. In vitro, we investigated the ability of LMWC-NAC conjugate uptake by renal tubular epithelial cells (HK-2) and the megalin receptor involved in the uptake process. In addition, the LMWC-NAC conjugate was labeled with indocyanine green, and its distribution in nude mice was investigated. The animal model of acute renal injury was established by intraperitoneal injection of lipopolysaccharide (20 mg 路kg ~ (-1). The serum creatinine, blood urea nitrogen, inflammatory factor TNF- 伪 and IL-1 尾 were measured after 72 h administration of lipopolysaccharide (LPS). The pathological changes of renal tissue were observed by HE staining. Results the LMWC-NAC conjugate was obtained by amide reaction. In vitro, the LMWC-NAC conjugate was absorbed by HK-2 cells mediated by megalin receptor. The in vivo distribution of the conjugate showed that LMWC-NAC conjugate had a better distribution in renal tissue after the tail vein injection of LMWC-NAC conjugate in AKI mice. Serum urea nitrogen and creatinine were significantly improved, inflammatory factors and oxidative stress indexes were also significantly decreased, and renal pathological damage was alleviated. Conclusion LMWC-NAC conjugate has better targeting and improving function on kidney, which indicates that it can be used in the treatment of acute renal injury.
【作者单位】：温州医科大学第二附属医院;宁波大学附属阳明医院;
【分类号】：R943

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