Synthesis and properties of crosslinked carboxymethyl chitosan and its hemostatic and wound healing effects on liver injury of rats
Synthesis and properties of crosslinked carboxymethyl chitosan and its hemostatic and wound healing effects on liver injury of rats
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DOI：
10.1177/0885328219852888
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发表时间：
2019-05
影响因子：
2.9
通讯作者：
Wei Zhang;Yu Xin;B. Yin;Guanlin Ye;Jun Wang;Jianfei Shen;Lei Li;Qi Yang
中科院分区：
文献类型：
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作者：
Wei Zhang;Yu Xin;B. Yin;Guanlin Ye;Jun Wang;Jianfei Shen;Lei Li;Qi Yang
羧甲基壳聚糖具有在止血材料领域应用的潜力，但其低分子量和高水溶性限制了其应用。本研究采用戊二醛交联法制备了交联羧甲基壳聚糖，并测定了其理化性质、红外光谱、对L929成纤维细胞的毒性和细胞形态。并对交联羧甲基壳聚糖的止血作用和对大鼠肝脏的修复作用进行了评价。将动物分为三组（n = 18）：对照组（Con）、Surgicel®组（Sur）和交联羧甲基壳聚糖组（C-CMC）。结果表明，制备的高粘度交联羧甲基壳聚糖对小鼠L929成纤维细胞无细胞毒性，对细胞形态无异常影响，出血时间和失血量明显短于Con和Sur（P < 0.05）。第7、14、21天酶活性分析显示，交联羧甲基壳聚糖能较早提高炎症因子酶（IL-1β、IL-6、TNF-α、IFN-γ）的活性，并能较快恢复至正常水平（P < 0.05）。交联羧甲基壳聚糖对大鼠肝脏酶活性的影响可反映其对创伤愈合的影响，可显著降低ALT和AST的酶活性（P < 0.05），显著提高VEGF的酶活性（7、14 d），21 d后降低（P < 0.05）。交联羧甲基壳聚糖具有潜在的临床止血生物材料的应用价值，目前的研究仅对交联羧甲基壳聚糖进行了基础研究，有待于进一步研究。
Carboxymethyl chitosan has the potential to be used in the field of hemostatic materials, but its low molecular weight and high water solubility limit its application. This study prepared crosslinked carboxymethyl chitosan by crosslinking reaction with glutaraldehyde and determined its physicochemical properties, FT-IR spectra, and toxicity and cell morphology on L929 fibroblasts. The hemostatic effect and healing function of crosslinked carboxymethyl chitosan on rat liver were also evaluated. The animals were divided into three groups (n = 18): control group (Con), Surgicel® group (Sur), and crosslinked carboxymethyl chitosan group (C-CMC). The results showed that crosslinked carboxymethyl chitosan with high viscosity was successfully prepared, which had no cytotoxicity and no abnormal effects on cell morphology to L929 fibroblasts of mouse, and had significantly shorter bleeding time and less blood loss compared to Con and Sur (P < 0.05). The enzyme activity analysis on 7, 14 and 21 days showed that crosslinked carboxymethyl chitosan can significantly elevate the activities of inflammatory factor enzymes at earlier time and restore them to normal level faster (IL-1β, IL-6, TNF-α, and IFN-γ) (P < 0.05). The wound healing effects of crosslinked carboxymethyl chitosan could be reflected by the enzyme activity on rat liver, which can significantly decrease the enzyme activities of ALT and AST (P < 0.05) and significantly increase the enzyme activity of VEGF on 7 and 14 days and decreased on 21 days (P < 0.05). The crosslinked carboxymethyl chitosan has the potential application of the clinical hemostasis biomaterial, and the present study only conducted a basic research of crosslinked carboxymethyl chitosan, and further investigations should be performed in future.