米诺环素对肝部分切除术后小鼠远期认知功能的影响

Effect of minocycline on long-term cognitive function after partial hepatectomy in mice

目的 评价米诺环素对肝部分切除术后小鼠远期认知功能的影响.方法 雄性C57BL/6小鼠64只,3月龄,体重约20 g,采用随机数字表法分为4组（n=16）：对照组（C组）、肝部分切除术组（O组）、PBS缓冲液组（PBS组）和米诺环素组（Mino组）.肝切除术模型制备后3d,C组和O组行Morris水迷宫实验,采用实时荧光定量PCR检测海马TNF-α和IL-6的mRNA表达,Western blot法检测海马核蛋白NF-κB表达.Mino组小鼠术毕苏醒后腹腔注射米诺环素50 mg· kg-1·d-1,PBS组给予等容量PBS,连续30 d,随后观测上述项目.结果 与C组比较,O组小鼠逃避潜伏期和游泳距离延长,海马TNF-α mRNA、IL-6 mRNA和核蛋白NF-κB表达上调（P＜0.05）；与PBS组比较,Mino组小鼠逃避潜伏期和游泳距离缩短,海马TNF-α mRNA、IL-6 mRNA和核蛋白NF-κB表达下调（P＜0.05）.结论 米诺环素可改善肝部分切除术后小鼠的远期认知功能,其机制与抑制海马炎性反应有关.

Objective To evaluate the effect of minocycline on the long-term cognitive function after partial hepatectomy in mice.Methods Sixty-four male C57BL/6 mice,aged 3 months,weighing about 20 g,were randomly divided into 4 groups （n =16 each） using a random number table：control group （group C）,partial hepatectomy group （group O）,PBS group,and minocycline group （Mino group）.At 3 days after partial hepatectomy,the rats underwent Morris water maze test.The animals were sacrificed and their hippocampi were immediately removed for determination of tumor necrosis factor-alpha （TNF-α） and interleukin-6 （IL-6） mRNA （using real-time fluorescent quantitative PCR） and nuclear factor kappa B （NF-κB） expression in the nuclcar protein of the cells （using Western blot）.After the mice regained consciousness after operation,minocycline 50 mg＆#183; kg-1 ＆#183; d-1 was injected intraperitoneally for 30 consecutive days in Mino group,while the equal volume of PBS was given instead of minocycline in group PBS.The parameters mentioned above were then recorded.Results Compared with group C,the escape latency and swimming distance were significantly prolonged,and the expression of TNF-α mRNA,IL-6 mRNA and NF-κB was up-regulated in group O （P 〈 0.05）.Compared with group PBS,the escape latency and swimming distance were significantly shortened,and the expression of TNF-α mRNA,IL-6 mRNA and NF-κB was down-regulated in group Mino （P 〈 0.05）.Conclusion Minocycline can improve the long-term cognitive function after partial hepatectomy in mice and inhibition of inflammatory responses in hippocampi is involved in the mechanism.