复方红景天提取物对大、小鼠脑缺血模型的保护作用

Protective Effects of Compound Rhodiola Extract on Cerebral Ischemia Models in Rats and Mice

关键词:  复方红景天提取物  脑缺血  大鼠  小鼠  caspase-3

Key words:  Compound Rhodiola extract  cerebral ischemia  rats  mice  caspase-3

摘要:

目的 研究复方红景天提取物对小鼠急性脑缺血和大鼠局灶性脑缺血模型的保护作用。方法 昆明小鼠随机分为假手术组、模型组、尼莫地平阳性对照组及复方红景天提取物高、中、低剂量组（2.18，1.09，0.55 g·kg^-1），灌胃给药7 d后结扎小鼠双侧颈总动脉合并迷走神经制备小鼠急性脑缺血模型，观察小鼠存活时间。SD大鼠随机分为假手术组、模型组、尼莫地平阳性对照组及复方红景天提取物高、中、低剂量组（1.45，0.73，0.36 g·kg^-1），线栓法制备大鼠大脑中动脉阻塞模型，复制模型前7 d开始灌胃给药，连续给药10 d。测定大鼠神经行为学及脑梗死比例，原位末端标记法检测神经细胞凋亡率，Western bolt检测caspase-3的表达水平。结果 复方红景天提取物高、中剂量组可延长小鼠存活时间，与模型组相比具有显著性差异（P<0.01或P<0.05）。与模型组相比，复方红景天提取物高、中剂量组能显著降低大鼠神经功能评分（P<0.01或P<0.05），复方红景天提取物各剂量组均能显著降低大鼠脑梗死比例并抑制皮质区神经细胞凋亡，下调caspase-3的表达（P<0.01或P<0.05）。结论 复方红景天提取物对大、小鼠脑缺血模型均具有保护作用，可明显延长急性脑缺血小鼠的存活时间，减轻局灶性脑缺血大鼠的神经功能损伤，缩小梗死灶，抑制神经细胞凋亡，其机制与下调caspase-3的表达有关。

Abstract:

OBJECTIVE To study the protective effects of Compound Rhodiola extract on acute cerebral ischemia in mice and focal cerebral ischemia in rats. METHODS KM mice were randomly divided into sham group, model group, nimodiping positive control group, and Compound Rhodiola extract high, medium and low dose groups(2.18, 1.09, 0.55 g·kg^-1). The acute cerebral ischemia model in mice was induced by ligaturing the bilateral carotid arteries and vagus nerve after 7 d of intragastric administration, and survival time was observed. SD rats were randomly divided into sham group, model group, nimodiping positive control group, and Compound Rhodiola extract high, medium and low dose groups(1.45, 0.73, 0.36 g·kg^-1). Middle cerebral artery occlusion(MCAO) models in rats were made with thread blocking method. Drugs were given to the rats 7 d before preparation of the models, ig for consecutive 10 d. The scores of nerve function and cerebral infarction proportion were measured. TUNEL method was used to evaluate the apoptosis of neurons. Western bolt method was used to detect the quantitative expression level of caspase-3. RESULTS The high and medium dose groups of Compound Rhodiola extract could prolong the survival time in mice with acute cerebral ischemia, and had significant difference compared with model group (P<0.01 or P<0.05). Compared with model group, the high and medium dose groups of Compound Rhodiola extract significantly reduced the scores of nerve function (P<0.01 or P<0.05); Each dose group of Compound Rhodiola extract significantly reduced the proportion of cerebral infarction, inhibited the apoptosis of cortex neurons in rats and down-regulated the caspase-3 expression (P<0.01 or P<0.05). CONCLUSION Compound Rhodiola extract has good protective effects on cerebral ischemia models in mice and rats. It can prolong the survival time in mice with acute cerebral ischemia, alleviate the nerve function damage, reduce the proportion of cerebral infarction and inhibite the apoptosis of neurons in MCAO rats. The mechanism is related to the down-regulation of the expression of caspase-3.