下调PTEN基因对慢性偏头痛大鼠NR2B亚基酪氨酸磷酸化和一氧化氮的影响

The effects of PTEN gene down-regulation on the NR2B-pTyr expression and NO in rat model of chronic migraine

目的利用RNAi重组腺病毒下调第10号染色体同源缺失性磷酸酶-张力蛋白基因(PTEN)的表达,探讨PTEN基因对慢性偏头痛大鼠三叉神经脊束核尾核(TNC)内N-甲基-D-天冬氨酸受体2B亚基酪氨酸磷酸化(NR2B-pTyr)蛋白表达水平和一氧化氮(NO)含量的影响。方法将SD雄性大鼠分为对照组、对照干预组、模型组和模型干预组。硬脑膜滴注炎性汤(IS)建立慢性偏头痛大鼠模型,TNC注射AdR-siPTEN,7d后观察大鼠行为学改变,检测大鼠TNC内PTEN、NR2B-pTyr和NO含量。结果 AdR-siPTEN可下调慢性偏头痛大鼠模型TNC中PTEN的表达;与模型组比较,IS干预慢性偏头痛大鼠的行为学症状明显缓解,大鼠的TNC内NR2B-pTyr表达水平及NO水平明显减少,差异均有统计学意义(P<0.05)。结论 PTEN参与调节慢性偏头痛的病理过程,下调PTEN基因可缓解IS诱导的慢性偏头痛大鼠的疼痛行为学,其机制可能与下调PTEN引起NR2BpTyr表达量及NO水平降低有关。

Objective To employ the RNAi recombinant adenovirus to knock down the expression of phosphatase and tensin homolog deleted on chromosome ten（PTEN） gene, and ＇to explore the effects of PTEN gene on the expression of tyrosine phosphorylation of the NR2B subunit and nitric,oxide（NO） in the trigeminal nucleus caudalis（TNC） of rats with inflammatory soup-induced chronic migraine. Methods SD rats were divided into the control groups（with or without intervention） and model groups（with or without intervention）. The chronic migraine rat model was established by pumping inflammation soup（IS） to the rat dura mater, and injected AdR-siPTEN into the TNC of rat after the last time pumping IS. The behaviors change of migraine rats was observed,and the expression of PTEN,NR2B-pTyr and NO in TNC of migraine rats was detected 7 days after injecting AdR-siPTEN. Results The expression of PTEN gene in TNC of rate model of chronic migraine was down-regulated by the localized injection of AdR- sipTEN. Compared with the model group,behavioral symptoms of IS-induced rats were obviously relieved, and the expression of PTEN,NR2B-pTyr and NO production in TNC of IS-induced rats was significantly decreased, there was statistically significant difference（P〈0.05）. Conclusion PTEN may play an important rote in the pathological mechanism of chronic migraine. Down-reg- ulating PTEN gene.expression can relieve IS-induced pain-related behaviors of rats with chronic migraine, which may be related to the decrease of NR2B-pTyr expression and NO production induced by down-regulation of PTEN.