摘要
目的观察红景天对链脲佐菌素(STZ)诱导的糖尿病模型大鼠认知功能障碍的影响,并探讨其相关作用机制。方法选择SD大鼠45只,按随机数字表法分为正常对照组、糖尿病模型组及红景天组,每组15只。采用腹腔注射STZ(60mg/kg)的方法复制糖尿病大鼠模型(注射72h后用血糖仪测定尾静脉血糖〉16.7mmol/L视为糖尿病模型制备成功);正常对照组大鼠腹腔注射等体积柠檬酸盐缓冲液。制模后红景天组给予红景天15mg/kg灌胃,正常对照组和糖尿病模型组给予等体积生理盐水灌胃,均每日1次。连续治疗4周后用Morris水迷宫实验检测大鼠认知功能;观察制模前后各组大鼠的血糖水平;采用蛋白质免疫印迹试验(WesternBlot)和酶联免疫吸附试验(ELISA)检测各组大鼠海马肿瘤坏死因子-α(TNF-α)和白细胞介素-6(IL-6)的蛋白表达水平和含量。结果与正常对照组比较,糖尿病模型组逃避潜伏期明显延长(s:62.54±7.67比19.37±4.23),目标象限停留时间缩短(s:18.76±4.75比43.09±8.09),跨越平台次数明显减少(次:2.26±0.57比6.84±1.56),而血糖水平明显增高(mmol/L:24.27±3.69比6.95±1.52),海马TNF-α和IL-6含量和蛋白表达水平均明显增加[TNF-α(μL):482.09±45.72比92.53±14.84,IL-6(μg/L):8.26±1.14比3.03±0.48;TNF-α蛋白(A值):0.61±0.15比0.25±0.04,IL-6蛋白(A值):0.53±0.11比0.12±0.03,均P〈0.05]。与糖尿病模型组比较,红景天组大鼠逃避潜伏期缩短(s:38.07±5.84比62.54±7.67),目标象限停留时间延长(s:31.29±5.61比18.76±4.75),跨越平台次数增多(次:4.72±1.24比2.26±0.57),血糖水平明显降低(mmol/L:18.34±2.75比24.27±3.69),海马TNF-α[和IL-6的含量和蛋白表达水平均明显降低[TNFα(μg/L):328.46±39.33比482.09±45.72,IL-6(μL):6.09±0.97比8.26±1.14;TNF-α蛋白(A值):0.47±0.09比0.61±0.15,IL-6蛋白(A值):0.28±0.06比0.53±0.11,均P〈0.05]。结论红景天可改善STZ诱导的糖尿病模型大鼠的认知损害,其作用机制可能与降低糖尿病大鼠海马炎症反应和血糖水平有关。
Objective To observe the effect of salidroside on the cognitive dysfunction of rats with diabetes induced by streptozotocin (STZ) and to explore its related mechanisms. Methods According to the random number table method, 45 Sprague-Dawley (SD) rats were divided into three groups: the normal control, diabetic model and salidroside groups, 15 rats in each group. The diabetic rat model was established by intra-peritoneal injection of 60 mg/kg STZ (72 hours after STZ injection, the caudal venous blood glucose was measured by a glucose meter, if the glucose level reached 〉16.7 mmol/L , the model was regarded as a successful one). The rats in the normal control group were injected with equal volume of citrate buffer. After model making, the salidroside group was treated with salidrosidec 15 mg/kg by intragastric administration; the normal control group and the diabetic model group were given the same volume of normal saline for gavage, 1 times a day. Morris water maze was used to test cognitive function in rats after consecutive four weeks of treatment, and the blood glucose levels of rats in various groups were detected at the onset and the end of the experiment; the protein expression and contents of tumor necrosis factor- α (TNF- α ) and intedeukin-6 (IL-6) in hippocampus were detected by enzyme linked immnnosorbent assay (ELISA) and Western Blot analysis. Results Compared with the normal control group, the escape latency in diabetic model group was significantly prolonged (seconds: 62.54±7.67 vs. 19.37 ±4.23), the time in target quadrant was shortened (seconds: 18.76 ± 4.75 vs. 43.09 ±8.09), the number of crossing platform was also obviously reduced (frequency: 2.26 ± 0.57 vs. 6.84±1.56), blood glucose levels were significantly higher (mmol/L: 24.27 ±3.69 vs. 6.95±1.52), protein expressions and contents of TNF-oL and IL-6 in hippocampus were markedly increased [TNF-α (μg/L): 482.09±45.72 vs. 92,53 ± 14.84, IL-6 (μg/L): 8.26 ±1.14 vs. 3.03 ± 0.48; TNF- αprotein (A value): 0.61 ±0.15 vs. 0.25± 0.04, IL-6 protein (A value): 0.53±0.11 vs. 0.12±0.03, all P 〈 0.05]. Compared with the diabetic model group, the escape latency in salidroside group was significantly shortened (seconds: 38.07 ±5.84 vs. 62.54± 7.67), the time in target quadrant was prolonged (seconds: 31.29±5.61 vs. 18.76 ± 4.75), the number of crossing platform was also significantly increased (frequency: 4.72±1.24 vs. 2.26±0.57), blood glucose levels were obviously lowered (retool/L: 18.34± 2.75 vs. 24.27 ±3.69), protein content and expression of TNF-ct and IL-6 in hippocampus were remarkably decreased [TNF- α (μg/L): 328.46 ±39.33 vs. 482.09± 45.72, IL-6 (μg/L): 6.09 ± 0.97 vs. 8.26 ± 1.14; TNF- α protein (A value): 0.47± 0.09 vs. 0.61 ±0.15, IL-6 protein (A value): 0.28 ±0.06 vs. 0.53 ±0.11, all P 〈 0.05]. Conclusion Salidroside can ameliorate the cognitive impairment in STZ-induced diabetic rats, and its mechanism may be closely related to the reduction of the hippocampal inflammatory response and blood glucose level of diabetic rats.
作者
刘娜
王晓
孟莉
王培芝
王铭维
Liu Na;Wang Xiao;Meng Li;Wang Peizhi;Wang Mingwei(Department of Neurology,the First Hospital of Hebei Medical University,Shijiazhuang 050031,Hebei,China)
出处
《中国中西医结合急救杂志》
CAS
CSCD
北大核心
2018年第3期233-236,共4页
Chinese Journal of Integrated Traditional and Western Medicine in Intensive and Critical Care
关键词
糖尿病
大鼠
认知功能
链脲佐菌素
水迷宫
红景天
Diabetes
Rat
Cognitive function
Streptozotocin
Morris water maze
Salidroside