雷公藤红素对肝叶部分切除老年小鼠术后认知功能及海马Tau蛋白磷酸化的影响

目的：观察肝叶部分切除术后老年小鼠认知功能的变化及海马内Tau蛋白磷酸化位点Ser396、Ser199/202的变化和雷公藤红素对老年小鼠术后认知功能障碍时的神经保护作用。方法：C57BL/6老年小鼠随机分为3组（n=48）：假手术组（S组）、肝叶部分切除术组（O组）和肝叶部分切除术加雷公藤红素组（C组）。每组再根据不同时间点分为12h、1d、3d和7d4个亚组,每个时间点12只动物。三组小鼠采用Mor-ris水迷宫检测小鼠认知功能,免疫组织化学法和Western blotting方法检测各组小鼠海马Tau蛋白磷酸化的变化。结果：与S组同时点比较,O组术后3d和7d时水迷宫成绩下降（P〈0.05）;C组术后3d和7d水迷宫成绩好于O组（P〈0.05）,而与S组接近（P〉0.05）。免疫组织化学染色阳性数和Western blotting显示O组Tau蛋白磷酸化位点Ser396、Ser199/202表达多于S组（P〈0.01）,而C组表达少于O组（P〈0.01）,与S组接近（P〉0.05）。结论：雷公藤红素对老年小鼠肝叶部分切除术造成的认知功能障碍具有明显的保护作用,其机制可能与抑制Tau蛋白异常磷酸化有关。

Effect of Celastrol on cognitive function and Tau hyperphosphorylation in eldly mice hippocampus after partial hepatectomy

AIM：To observe the expression of Tau phosphorylation in hippocampus and cognitive function deficit on eldly mice induced by partial hepatectomy.As well as the neuroprotective effect of Celastrol on postoperative cognitive dysfunction.METHODS：The C57BL/6 eldly mice were randomly assigned to three groups（n =48）：Sham operation group（group S）,operation group（group O）underwent partial hepatectomy and the Celastrol treatment was given to the operation group（group C）.According to the different time point,each group（n=12）was divided 12 h,1,3 and 7 d,respectively.The cognitive function in three groups was detected by Morris water maze test;the changes of Tau phosphorylation were measured by immunocytochemistry/Western blotting.RESULTS：Compared with the Group S,the results of the Morris water maze test were significantly decreased in Group O at 3,7 d（P0.05）;compared with Group O,the results of the Morris water maze test in Group C were obviously increased（P0.05）,approached the Group S（P0.05）.Compared with Group S,the immunochemistry staining of brain slice and Western blotting showed that the expressions of Tau pSer404,pSer199/202 in Group O were markedly increased（P0.01）.The level of Tau hyperphosphorylation in Group C was markedly decreased comparing to those in Group O（P0.01）and approached the Group S（P0.05）.CONCLUSION：Celastrol can improve cognitive dysfunction induced by partial hepatectomy in eldly mice,the mechanism is correlated with Tau hyperphosphorylation inhibited.