乌龙丹对慢性脑缺血大鼠松果体钟基因表达的影响

Effects of Wulongdan on expression of pineal clock genes in rats with chronic cerebral ischemia

目的初步探讨慢性脑缺血对大鼠睡眠钟基因表达的影响及乌龙丹对其的调控作用。方法 24只雄性SD大鼠随机分为假手术组、模型组、乌龙丹给药组。采用改良式双侧颈总动脉永久性结扎法建立大鼠慢性脑缺血模型,造模3周后,灌胃给药3周,并持续监测各组大鼠体重,应用实时荧光定量PCR检测大鼠松果体钟基因Clock、Bmal1、Per1表达的变化。结果模型组较假手术组Clock mRNA、Per1mRNA表达显著降低(P<0.01,P<0.05),Bmal1基因表达无显著差异(P>0.05);乌龙丹给药组的Clock基因水平高于模型组(P<0.01),Bmal1基因表达较假手术组降低(P<0.05),Per1无显著变化(P>0.05)。结论慢性脑缺血可能成为睡眠障碍的潜在病因,乌龙丹对慢性脑缺血引起的睡眠障碍有一定的治疗作用。

Objective To explore the changes in the expression of pineal clock genes in rats with chronic cerebral ischemia and evaluate the effect of intervention with Wulongdan,a traditional Chinese medicinal preparation,on these changes.Methods Male SD rats were randomly divided into sham-operated group,chronic cerebral ischemia model group,and treatment group.In the latter two groups,chronic cerebral ischemia was induced by permanent ligation of the bilateral carotid arteries,and in the treatment group,Wulongdan was administered intragastrically on a daily basis for 3 weeks after the operation.Real-time quantitative RT-PCR was employed to examine the changes in the pineal expressions of Clock,Bmal1,and Per1 mRNA after the treatment.Results In the model group,the expression levels of Clock and Per1 mRNA were significantly lowered compared to those in the sham-operated group（P0.01,P0.05）,but Bmal1 mRNA expression showed no significant changes（P0.05）.Wulongdan treatment caused a significant increase in pineal lock mRNA expression compared to the model group（P0.01）,and significantly reduced pineal Bmal1 expression as compared to the sham-operated group（P0.05）.No significant difference was found in Per1 mRNA expression between the treatment group and the model group.Conclusion The changes in the expressions of the pineal clock genes in rats with chronic cerebral ischemia suggest the association between chronic cerebral ischemia and sleep disorders.Wulongdan can mitigate sleep disorders caused by chronic cerebral ischemia.