竹叶石膏汤改善2型糖尿病大鼠记忆功能衰退症状的作用机制

Mechanism of Lophatherum and Gypsum Decoction ameliorating the memory decline symptoms in type 2 diabetic rats

目的观察竹叶石膏汤对2型糖尿病大鼠学习记忆能力减退症状的改善作用并探讨其机制。方法取8周龄雄性大鼠10只,体重300~340 g,设为正常组;另取72周龄,体重500~560 g,雄性大鼠50只,采用高糖高脂饮食结合小剂量链脲佐菌素(STZ,45 mg/kg)诱导2型糖尿病大鼠模型,将造模成功的大鼠随机分为模型组,低剂量组、高剂量组,每组10只,低剂量及高剂量组每天灌胃竹叶石膏汤水煎液,模型组与正常组每天灌胃等体积生理盐水,连续给药14 d后,用Morris水迷宫检测大鼠学习记忆能力,并检测大鼠空腹血糖、口服葡萄糖耐量(OGTT)、空腹胰岛素水平及海马组织中肿瘤坏死因子(TNF)-α、β淀粉样蛋白(Aβ)1~42含量。结果行为学实验结果显示:低剂量组大鼠中央区停留时间和穿越平台次数均比模型组显著升高(P<0.01);生化指标检测结果显示:高剂量及低剂量组大鼠空腹血糖水平均比模型组显著降低(P<0.01),海马TNF-α水平显著降低(P<0.05),但海马Aβ1~42水平变化不明显(P>0.05)。结论竹叶石膏汤可增强2型糖尿病大鼠学习记忆能力,其机制可能与抑制大鼠海马TNF-α的过度表达有关。

Objective To observe the improvement effect and mechanism of Lophatherum and Gypsum Decoction on the memory decline symptoms in type 2 diabetic rats.Methods 10 male rats(aged 8 weeks,weight 300~340 g)were set as normal control group,other 50 male rats(aged 72 weeks,weight 500~560 g)were fed with high-fat diet and intraperitoneal(ip)injection of low dose streptozotocin(STZ,45 mg/kg)to induce type 2 diabetic rat model.Rats with hyperglycemia were divided into model control,high and low dose of Lophatherum and Gypsum Decoction groups with 10 rats in each group.Rats in low and high dose of Lophatherum and Gypsum Decoction groups were intragastric(ig)administrated with different doses of Lophatherum and Gypsum Decoction,rats in model and normal control groups were ig administrated with equal volume of normal saline for 14 days.Morris water maze was used to detect the learning and memory abilities of rats,moreover,the levels of fasting blood glucose and insulin in serum and the contents of tumor necrosis factor(TNF)-αandβ-amyloid(Aβ)1~42 in hippocampus were detected.Results The results of behavioral experiment showed that low dose of Lophatherum and Gypsum Decoction intervention significantly increased the residence time in central area and the times of rats crossing the original platform in the probe trial(P<0.01).In addition,the results of biochemical examination showed that both low and high dose of Lophatherum and Gypsum Decoction intervention could significantly reduce the serum levels of fasting blood glucose(P<0.01)and decrease the content of TNF-αin hippocampus of diabetic rats(P<0.05),however,the content of Aβ1~42 in hippocampus was not significantly decreased(P>0.05).Conclusions Lophatherum and Gypsum Decoction could ameliorate the memory decline symptoms of type 2 diabetic rats,the mechanism might be related to inhibiting excessive secretion of TNF-αin hippocampus.