本文選題：乙酰半胱氨酸 + 低相對分子質(zhì)量殼聚糖　； 參考：《中國藥學(xué)雜志》2017年08期

【摘要】：目的合成低相對分子質(zhì)量殼聚糖-乙酰半胱氨酸(LMWC-NAC)偶合物,并且評價其在急性腎損傷模型動物體內(nèi)的腎臟靶向性及療效。方法以碳二亞胺/N-羥基琥珀酰亞胺為縮合劑,將乙酰半胱氨酸通過酰胺反應(yīng)嫁接到低相對分子質(zhì)量殼聚糖上,并且采用核磁共振進(jìn)行結(jié)構(gòu)確證。在體外細(xì)胞實驗中,考察LMWC-NAC偶合物被腎小管上皮細(xì)胞(HK-2)攝取的能力以及參與攝取過程的megalin受體。此外,用熒光材料吲哚菁綠標(biāo)記LMWC-NAC偶合物,并對其在裸鼠體內(nèi)的分布情況進(jìn)行考察。腹腔注射脂多糖(20 mg·kg~(-1))構(gòu)建急性腎損傷動物模型,給藥72 h后檢測各組小鼠的血肌酐、血尿素氮、炎癥因子(TNF-α和IL-1β)、氧化應(yīng)激(MDA),HE染色觀察腎臟組織的病理學(xué)改變。結(jié)果通過酰胺反應(yīng)得到LMWC-NAC偶合物,體外實驗證實其通過megalin受體的介導(dǎo)被HK-2細(xì)胞攝取,而體內(nèi)分布實驗表明,LMWC-NAC偶合物在腎臟組織具有較好的分布,AKI小鼠尾靜脈注射LMWC-NAC偶合物后,血清尿素氮和肌酐得到顯著改善(P0.01),炎癥因子和氧化應(yīng)激指標(biāo)也顯著下降(P0.01),減輕腎臟病理損傷。結(jié)論 LMWC-NAC偶合物對腎臟具有較好的靶向性和改善其功能的能力,表明其可用于急性腎損傷的治療。
[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- 偽 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.
【作者單位】： 溫州醫(yī)科大學(xué)第二附屬醫(yī)院;寧波大學(xué)附屬陽明醫(yī)院;
【分類號】：R943

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