阿米替林可上调SNI大鼠脊髓的GLT-1蛋白表达

AMITRIPTYLINE UP-REGULATES GLT-1 IN SPINAL CORD OF SPARED NERVE INJURED RAT

目的：观察阿米替林（amitriptyline,AM I）对SNI（spared nerve injury）大鼠脊髓谷氨酸转运体-1（glutamate transporter subtype 1,GLT-1）表达的影响。方法：体重180-200 g的雄性SD大鼠随机分为4组：对照组（A）、SNI模型组（B）、AM I组（C）、SNI模型＋AM I组（D）,经腹腔注射0.2m l生理盐水（A和B）、10mg/kg AM I（C和D）,每日两次。术后1、3、5 d取各组大鼠L3-L6脊髓,检测GLT-1蛋白和mRNA表达改变,同时使用Von Frey纤维测量大鼠手术侧机械痛阈值（mechanicalpain threshold）改变。结果：与A组相比,B组大鼠脊髓内GLT-1蛋白和mRNA术后1 d均表达增高,但术后3、5 d逐渐降低,同时机械痛阈值随时间下降,C组大鼠GLT-1表达随时间逐渐增加,但是机械痛阈值无明显改变,D组大鼠术后GLT-1表达较A组明显增高,但不随时间变化,给药后3、5 d机械痛阈值显著高于B组。结论：AMI可以增加GLT-1蛋白表达,可能是治疗神经病理性疼痛的机制之一。

Objective： To investigate influence of amitriptyline on glutamate transporter subtype 1 （GLT- 1 ） in spinal cord of rats after spared nerve injury （SNI）. Methods： Male Sprague-Dawley rats weighing 180 - 200 g were divided into four groups ： control （ A）, SNI （ B）, amitriptyline （C） and SNI ＋ amitriptyline （D） groups, which respectively received intraperitoneal injections of 0.2ml saline （A and B）, 10mg/kg amitriptyline （C and D）, bid. The L3 -6 segments of the spinal cord were isolated in 1,3 and 5 days after surgery. Expression of GLT-1 was determined by Western blot and RT-PCR. The mechanical pain threshold of the rats before and after the operation was determined with a Von Frey hair test. Re- sults ： The expression of GLT-1 at both protein and mRNA level in group B was higher than that in control on day 1 after operation followed with a decrease in expression on day 3 and 5. A decreased rat mechanical pain threshold was showed in group B. In group C, the expression of GLT-1 increased gradually and there were no changes of the mechanical pain threshold. The expression of GLT-1 in group D was higher than that in control and did not change on days 1, 3 and 5. The mechanical pain threshold in group D was higher than that in group B on days 3 and 5 after operation. Conclusions： Amitriptyline could increase the expression of GLT-1 which may be one of its mechanisms in the treatment of neuropathie pain.