降钙素原在大鼠脓毒症引起认知功能障碍中的关系研究

The potential role of PCT in sepsis rats with cognitive dysfunction

目的:探讨降钙素原(PCT)在大鼠脓毒症引起认知功能障碍中的作用。方法:60只成年雄性SD大鼠随机分为假手术组(C组)、脓毒症组(S组)、脓毒症+米诺环素组(SM组),每组各20只。采用盲肠结扎穿孔(CLP)术建立脓毒症模型,造模后观察各组大鼠7 d生存率,应用Morris水迷宫实验和条件恐惧实验检测各组大鼠认知情况,RT-PCR和Western Blot检测各组大鼠海马组织中PCT表达量。结果:与C组相比,S组存活率显著降低(P<0.001);与S组比较,SM组存活率增加(P<0.05);C组和S组存活率比较,差异无统计学意义(P>0.05);各组大鼠7 d生存率为:C组100%、S组54.5%、SM组85.0%。Morris水迷宫实验结果显示,与C组比较,S组和SM组跨越目标象限次数减少(P<0.01),平台潜伏期延长(P<0.01);与S组比较,SM组平台潜伏期缩短(P<0.01),跨越目标象限次数增多(P<0.01)。恐惧记忆测试结果显示,在情景测试和声音测试中,与C组比较,S组大鼠静止时间明显缩短(P<0.01);与S组比较,SM组大鼠静止时间延长(P<0.01),C组和S组比较差异无统计学意义(P>0.05)。RT-PCR和Western Blot结果显示,与C组比较,S组和SM组海马PCT表达明显升高(P<0.01);与S组比较,SM组海马PCT表达明显下降(P<0.05)。结论:脓毒症可引起大鼠认知功能损害,其机制可能与脑内海马PCT表达上调引起的中枢神经系统损害有关,有效抑制PCT可改善脓毒症引起的认知功能障碍。

Objective:To investigate the potential role of procalcitonin(PCT)in cognitive impairment by cecalligation and puncture sepsis rats model.Methods:60 SD rats aged 3 months were randomly divided into sham control(group C),sepsis(group S),and sepsis+minocycline group(group SM),20 cases in each group.The sepsis model was established by cecal ligation and perforation(CLP).The 7-day survival rate of rats in each group was observed after modeling.The cognitive status of rats in each group was detected by Morris water maze test and conditioned fear test.The expression of PCT in hippocampus of rats in each group was detected by RT-PCR and Western blot.Results:Compared with group C,the survival rate of group s was significantly lower(P<0.001).Meanwhile,the survival rate in group SM were increased compared with group S(P<0.05),there was no significant difference in survival rate between group C and group S(P>0.05).The 7-day survival rate of rats in each group was 100%in group C,54.5%in group s and 85.0%in group SM.The results of Morris water maze experiment showed that compared with group C,the times of crossing target quadrant in group S and SM decreased(P<0.01),and the latency of platform prolonged(P<0.01),compared with group S,the latency of platform shortened(P<0.01),and the times of crossing target quadrant increased(P<0.01).Conditional fear test showed that the freezing time of group S was significantly shorter than that of group C on the second day of context and cue tone(P<0.01)and these two sets of data in group SM were significantly increased when compared with group S(P<0.01),There was no significant difference between group C and group S(P>0.05).ELISA and Western Blot showed that the expression of PCT in hippocampus of group S,group SM were significantly increased when compared with C group(P<0.01),when compared with group S,group SM was significantly decreased(P<0.05).Conclusion:Sepsis can cause cognitive impairment in rats,the mechanism may be related to the upregulation of PCT in the brain,effective inhibition of PCT can improve the cognitive impairment caused by sepsis.