研究不同裂解程度褐藻寡糖的生物相容性及其对创面愈合的影响。

依赖分子量差异，通过透析法分离不同裂解程度褐藻寡糖，分子量分别为<1000、1000~5000、5000~10000、>10000，并采用未裂解的褐藻胶作为对照。观察不同分子量褐藻寡糖成膜能力，检测成膜后的阻菌性、保湿性，根据GB/T 16886的要求，检测细胞毒性、致敏反应、皮内刺激，验证生物相容性。SD大鼠背部制备直径3 cm的全层创面缺损模型，采用不同裂解程度褐藻寡糖溶液换药，分别为实验组1~4，褐藻胶溶液换药作为阳性对照组，生理盐水换药作为阴性对照组。每日换药，在第7天和第14天计算创面愈合率，并取创面组织行HE染色观察组织变化，行天狼星红－苦味酸染色观察胶原蛋白分泌情况。

当分子量<1000时，未能观察到成膜表现，且无明显阻菌性及保湿性。随着分子量增加，成膜能力、阻菌性及保湿性增强。不同分子量褐藻寡糖及未裂解褐藻胶在0.02%浓度下均无明显细胞毒性、致敏性，但当分子量<1000时，具有轻微皮内刺激反应。造模后第7天和第14天，除实验组2外，实验组各组及阳性对照组创面愈合率均明显高于阴性对照组(F＝0.018、0.097、0.016、0.055，t＝3.737、3.853、3.861、3.525；P<0.05; F＝0.562、0.111、1.162、0.206，t＝3.484、－1.557、－0.319、3.851；P<0.05)。HE和天狼星红－苦味酸染色提示分子量达到5 000以上时，肉芽组织增生明显，胶原蛋白含量增高。

低裂解程度的褐藻寡糖具有成膜、阻菌和保湿能力，能为创面提供适于愈合的湿润环境。

To study the biocompatibility of alginate oligosaccharides with different degree of lysis and effect on wound healing.

Depending on the difference of molecular weight, the alginate oligosaccharides with different degree of lysis were separated by dialysis method. The molecular weight was <1000, 1000-5000, 5000-10000 and >10000 respectively, and the non-cleaved alginate was used as control. Observed the film formation ability of alginate oligosaccharides with different molecular weight, detected the bacteria resistance and moisture retention after film formation ability, and detected the cytotoxicity, sensitization and intradermal stimulation according to the requirements of GB/T 16886 to verify the biocompatibility. A full-thickness wound defect model with a diameter of 3 cm was prepared on the back of SD rats. Alginate oligosaccharide solution with different degrees of lysis was used for dressing change, which was divided into experimental group 1-4, alginate solution as the positive control group, and physiological saline as the negative control group. The dressing was changed daily. The wound healing rate was calculated on the 7th and 14th days.The wound tissue was taken for HE staining to observe the tissue changes, and sirius red picric acid staining was used to observe the collagen secretion.

When the molecular weight was less than 1000, no film formation was observed, and there was no obvious bacteria resistance and moisture retention. With the increase of molecular weight, the film formation ability, bacteria resistance and moisture retention were enhanced. At the concentration of 0.02%, the alginate oligosaccharides with different molecular weight and non-cleaved alginate had no obvious cytotoxicity and sensitization, but when the molecular weight was less than 1 000, it had slight intradermal stimulation. On the 7th and 14th day after modeling, except for experimental group 2, the wound healing rate of each group in the experimental group and the positive control group was significantly higher than that of the negative control group(F=0.018, 0.097, 0.016, 0.055; t=3.737, 3.853, 3.861, 3.525; P<0.05; F=0.562, 0.111, 1.162, 0.206; t=3.484, -1.557, -0.319, 3.851; P<0.05). HE and sirius red picric acid staining showed that when the molecular weight was above 5 000, the granulation tissue proliferation and collagen content increased significantly.

The algal oligosaccharides with low degree of lysis has the ability of film formation, bacteria inhibition and moisture retention, and can provide a moist environment suitable for wound healing.