壳寡糖及其衍生物对糖尿病大鼠糖耐量及肠道微生态平衡的影响

Effect of chitooligosaccharides and its derivatives on oral glucose tolerance test and intestinal microecological balance in diabetic rats

目的:研究不同剂量的壳寡糖和N-乙酰氨基单糖对STZ诱导的糖尿病大鼠的糖耐量作用及肠道微生态平衡的影响.方法:按65 mg/kg体质量一次性ip STZ制备糖尿病大鼠模型.大鼠随机分为9组:正常对照组,二甲双胍阳性对照组,阴性对照组,壳寡糖高、中、低剂量组,N-乙酰氨基单糖高、中、低剂量组.正常对照组、阴性对照组每天灌胃蒸馏水(10 mL/kg);二甲双胍阳性对照组每天200 mg/kg灌胃;壳寡糖、N-乙酰氨基单糖组分别按250,500,1500 mg/kg每天灌胃,连续60 d,然后观察各组大鼠的一般状况和饮食.按2.5 g/kg体质量葡萄糖水溶液灌胃(ig),测定各组大鼠0,0.5,1,2h耐糖血糖值,并分别对各组大鼠肠道菌群进行培养,计数并计算B/E值.结果:不同剂量的壳寡糖和N-乙酰氨基单糖均能不同程度改善糖尿病大鼠的体质量减轻、多饮、多食等症状,中、高剂量组的效果要优于低剂量组.各模型组的葡萄糖糖耐量均有不同程度受损.壳寡糖各组葡萄糖耐量的显著改善(P<0.01),中剂量组效果最好;N-乙酰氨基单糖低剂量和中剂量显著改善葡萄糖耐量(P<0.05),低剂量组的效果最好.糖尿病大鼠肠道内大肠肝茵和肠球菌数量升高,而乳酸杆菌和双歧杆菌的数量明显下降.壳寡糖各剂量组可明显降低大肠肝茵和肠球菌的数量(P<0.01),对双歧杆菌和乳酸杆菌的增殖作用也有显著作用(P<0.01),且改善效果随着剂量的增加而增加;N-乙酰氨基单糖各剂量组随着剂量的增加使大肠杆菌和肠球菌的数量降低,高剂量组乳酸杆菌的增殖作用显著提高(P<0.01).单纯糖尿病大鼠组需氧菌总数量升高,而厌氧菌总数量升高明显下降,厌氧菌与需氧茵之比及B/E值<1.壳寡糖各剂量组均可使B/E值显著升高(P<0.01);N-乙酰氨基单糖高剂量组厌氧茵总数显著改善(P<0.05).结论:不同剂量的壳寡糖和N-乙酰氨基单糖均能不同程度的改善糖尿病大鼠的体质量减轻、多饮、多食等症状,改善葡萄糖耐量,对肠道微生态有调节作用.

AIM： To investigate the effect of chitooligo-saccharides （COS） and N-acetylglucosamine （NAG） at different doses on oral glucose tolerance test （OGTT） and intestinal microecological balance in rats with diabetes induced by streptozotocin （STZ）. METHODS： The diabetic model of Wistar rats was duplicated with STZ intraperitoneally （65 mg/kg, once）. The rats were randomly divided into 9 groups： normal control, metformin, diabetes, COS-H, COS-M, COS-L, NAG-H, NAG-M, and NAG-L group. The rats in normal control and diabetes group were treated with distilled water （10 mL/kg）, and those in metformin group were treated with metformin （200 mg/ kg）. The rats in COS-H, COS-M and COS-L group received high-, moderate- and low-dose COS treatment （250, 500, 1500 mg/kg）, while those in NAG-H, NAG-M, and NAG-L group received high-, moderate- and low-dose NAG treatment （250, 500, 1500 mg/kg）. All the drugs were administered by gastric irrigation. Sixty days later, the general conditions were observed. OGTT was performed and the intestinal flora were cultured, calculated and identified. The value of B/E was also calculated. RESULTS： COS and NAG improved the symptoms such as decrease of body weight, overdrinking and over-eating in diabetic rats, and the effects of high and moderate doses were superior to those of low ones. The glucose tolerance was decreased in all the diabetic rats, but was improved significantly （P 〈 0.05） by different concentrations of COS （moderate dose produced the best effect） and low and moderate concentrations of NAG （low dose produced the best effect）. In diabetic rats, the numbers of pathogenetic E. Coli and Enterococcus were increased while those of Bifidobacteria and Lactobacillus were decreased. However, after administration with COS and NAG, the numbers of Bifdobacteria and Lactobacillus increased significantly, while those of pathogenetic E. Coli and Enterococcus decreased significantly （P 〈 0.01）. The effects were increased with the elevation of COS and NAG concentrations. In diabetic rats, the total numbers of aerobes were increased, while those of anaerobes were increased markedly. The ratio of anaerobes to aerobes and the value of B/E were less than one. COS enhanced the value of B/E, while NAG augmented the total numbers of anaerobes （P 〈 0.05）. CONCLUSION： COS and NAG have effective effects on the general clinical symptom, disorders of glucose tolerance at different concentrations, and they can modulate the imbalance of intestinal microecology.