化瘀克塞汤预处理对局灶性脑缺血大鼠HSP70表达的影响

Protective effects of the Huayu Kesai decoction pretreatment on the brains of rats with focal cerebral ischemia and its effect on HSP70 expression

目的探讨不同剂量化瘀克塞汤对大鼠局灶性脑缺血的保护作用及对热休克蛋白(heat shock protein,HSP)70表达的影响。方法采用线栓法制备大脑中动脉缺血模型。Wistar大鼠60只随机分为假手术组、缺血组、化瘀克塞汤预处理高剂量组(含生药2.34 g/mL,1 mL/100 g)、化瘀克塞汤预处理低剂量组(含生药1.17 g/mL,1 mL/100 g),造模前7 d灌胃给药,1次/d,假手术组与缺血组则相应给予生理盐水。持续性缺血6 h后处死动物,观测各组大鼠脑梗死体积,神经元受损程度,采用RT-PCR法和免疫组化方法分别检测缺血脑组织HSP70 mRNA和蛋白的含量。结果局灶性脑缺血6 h后,化瘀克塞汤预处理高、低剂量组可明显减轻神经元受损程度,降低脑梗死体积(P<0.01,P<0.05)。缺血组HSP70 mRNA及蛋白表达明显增强,化瘀克塞汤高剂量组与缺血组相比,HSP70 mRNA及蛋白表达水平明显较低(P<0.01,P<0.05),在低剂量组也较低(P<0.01,P<0.05)。结论化瘀克塞汤预处理可使局灶性脑缺血大鼠HSP70表达下降,可能与化瘀克塞汤对脑缺血的保护作用减轻了应激反应有关。

Objective To investigate the effects of Huayu Kesai decoction （HYKSD） pretreatment and its related mechanisms on the brains of rats with focal cerebral ischemia. Methods Focal brain ischemia was induced by the intraluminal suture MCA occlusion method, then the rats were randomly divided into four groups （ n = 15 per group） ： the sham-operated group, the ischemia group, the high dose HYKSD pretreatment group（2.34 g/mL, 1 mL/l00 g）and the low dose HYKSD pretreatment group（ 1.17 g/ mL, 1mL/100 g）. The HYKSD groups were treated with HYKSD for 7 days before MCAO, 1 time per day, whereas the sham-operated group and the ischemia group were given NS. The infarct volume of the rat brains in each group was determined, the neurons were observed under microscopy, and the HSP70 mRNA expression was determined by RT-PCR and the HSP70 protein expression by immtmohistochemistry 6 hours after ischemia. Results High and low dose HYKSD pretreatment can decrease the damage of neurons and the infarct volume of the brains. The expressions of mRNA and protein were remarkably increased in the ischemia group, and they were remarkably decreased by HYKSD. Conclusion HYKSD can inhibit the expression of HSP70 mRNA and protein, which may be related to its effect on brain protection against cerebral ischemia.