壳寡糖抑制ApoE基因敲除小鼠动脉粥样硬化的形成

Chitosan oligosaccharides Inhibit the Occurrence of Atherosclerosis in ApoE^(-/-) Mice

壳寡糖具有抗氧化、抗炎、降血糖、降血脂等丰富的保健活性,但壳寡糖对动脉粥样硬化的改善作用并不明确。为深入探究壳寡糖是否可改善动脉粥样硬化,喂食ApoE^(-/-)转基因小鼠高脂饲料以构建动脉粥样硬化小鼠模型。试验分别设置3组小鼠(n=10):正常小鼠喂食普通饲料的对照组;ApoE^(-/-)转基因小鼠喂食高脂饲料的模型组;ApoE^(-/-)转基因小鼠喂食高脂饲料并给药壳寡糖的给药组。给药组给予该模型小鼠聚合度2~6的壳寡糖隔天灌胃处理,处理剂量为150 mg·kg^(-1),整个动物试验持续12周。结果表明:小鼠的脏器指数分析结果显示,壳寡糖对疾病小鼠的体重无明显影响,但可促进脾脏增重[(0.11±0.01)g]。分析小鼠的血液细胞组成发现,壳寡糖可有效提高白细胞含量[(6.9±1.3)×10~9·L^(-1)]以及白细胞中淋巴细胞比例[(73.2±15.2)%],提示壳寡糖可提高小鼠的免疫能力。小鼠的血液生化指标结果表明,壳寡糖可显著降低疾病小鼠的谷草转氨酶[(150.8±25.5)U·L^(-1)]、乳酸脱氢酶[(1119.1±252.9)U·L^(-1)]及血液中胆固醇含量[(3.1±0.5)mmol·L^(-1)],几乎达到正常小鼠水平。对肝脏组织进行的苏木素伊红染色,证明壳寡糖可有效逆转肝脏脂肪滴的累积。用特异性血管细胞黏附分子1(VCAM-1)及细胞间黏附分子1(ICAM-1)的抗体对动脉弓组织进行免疫组织化学检测,发现壳寡糖能够明显改善动脉粥样硬化条件下VCAM-1及ICAM-1的过表达。本研究制备的壳寡糖可有效逆转ApoE^(-/-)转基因小鼠的动脉粥样硬化疾病,本壳寡糖或可应用于保健品中防治老年人动脉粥样硬化。

Chitosan oligosaccharides(COS)exert versatile bioactivities including anti-oxidative,anti-inflammatory,hypoglycemia and hypolipidemia effects.However,the modulation of COS on atherosclerosis remains unclear.To investigate whether COS could alleviate atherosclerosis,we efficiently built the atherosclerosis mouse model by feeding ApoE-/-mice with high fat diet.The experiment was carried out on three groups of mice(n=10):normal group,C57BL/6J mice fed with normal diet;atherosclerosis model group,ApoE-/-mice fed with high fat diet;treatment group,ApoE-/-mice fed with high fat diet and treated with COS.ApoE-/-mice were gavaged with COS with degree of polymerization 2-6 at dose of 150 mg/kg every another day for 12 weeks.Primarily,results from organ index showed that COS significantly stimulated the weight gain of spleen[(0.11±0.01)g].The composition of blood cells illustrated that COS could effectively increase the amount of white cells[(6.9±1.3)×109·L-1]and the proportion of lymphocyte cells[(73.2±15.2)%],indicating that COS may enhance the immune system.The analysis of blood biochemistry revealed that COS could reverse the serum contents of aspartate transaminase[(150.8±25.5)U·L-1],lactate dehydrogenase[(1119.1±252.9)U·L-1]and cholesterol[(3.1±0.5)mmol·L-1],which were close to normal range.Further,H&E staining suggested that lipid accumulation in liver was attenuated by COS treatment.Finally,immunohistochemical analysis of arterial arch proved that COS could suppress VCAM-1 and ICAM-1 overexpression in ApoE-/-mice.Our study demonstrated that COS from our lab could remarkably restore atherosclerosis in ApoE-/-mice,and may further be applied in functional food for preventing or treating atherosclerosis for elders.