Nlrp3敲减对cuprizone诱导的脱髓鞘小鼠焦虑症状的影响

Effect of Nlrp3 knockdown on cuprizone inducing demyelination in mice with anxiety symptoms

目的：探讨NOD样受体家族pyrin域3（Nod like receptor family pyrin domain containing 3,Nlrp3）对脱髓鞘损伤致小鼠焦虑情绪的影响.方法：雄性C57BL/6小鼠分为对照组、双环己酮草酰二腙（CPZ）模型组、CPZ＋Nlrp3 shRNA组和Nlrp3 shRNA组;将对照或Nlrp3 shRNA慢病毒分别立体定位注射至小鼠胼胝体.1周后,小鼠喂食CPZ并测量喂食期间小鼠体质量;开场实验检测小鼠活动区域与距离,LFB-PAS染色观察脱髓鞘程度.结果：CPZ喂食2周内,小鼠平均体质量急剧下降;到5周时,CPZ模型组平均体质量显著低于对照组与CPZ＋Nlrp3 shRNA组.行为学检测显示,对照组和CPZ＋ Nlrp3 shRNA组小鼠后肢站立次数较CPZ模型组明显减少,而中央区域活动距离与活动总距离的比值CPZ模型组显著增加.LFB-PAS染色显示CPZ模型组胼胝体膝部髓鞘几乎完全缺失,其髓鞘化评分显著低于正常和CPZ＋ Nlpr3shRNA组.结论：Nlrp3敲减可缓解CPZ诱导的小鼠髓鞘脱失,并改善其焦虑症状.

Objective To investigate the effect of Nod like receptor family pyrin domain containing 3（Nlrp3） on the anxietycaused by demyelination in mice. Methods： 8-week-Old C57BL/6 male mice were divided into control group , cuprizone（CPZ）group , CPZ＋Nlrp3 shRNA group and Nlrp3 shRNA group, scramble or Nlrp3 shRNA lentivirus was stereotaxically injectedto corpus collasum in mice. One week later , demyelinating model was induced by 0. 2% （w/w） cuprizone diet and body weight was recorded for 5 weeks. Open field test was performed to detect the trajectory and distance on each mouse. To observe the degree of demyelination , LFB-PAS staining was conducted. Results： During the first 2 weeks,a drastic decline of body weight was detected in the mice treated with cuprizone. At the 5th week after cuprizone treatment,the average weight of mice in CPZ group was significantly lower than that in control group and CPZ＋Nlrp3 shRNA group. The number of rearing in the control group and the shRNA CPZ＋Nlpr3 group was significantly increased compared with the CPZ group , and the ratio of central and totll distance was significantly decreased. LFB-PAS staining showed almost complete demyelination in corpus callosum in the CPZ treated mice. Myelination score was significantly decreased in the CPZ group compared with that in the control and CPZ＋Nlpr3 shRNA group. Conclusion： Nlrp3 knockdown can partly alleviate the demyelination caused by cuprizone , so as to improve the anxiety symptoms of mice.