姜黄素对阿尔茨海默病大鼠学习记忆及HMGB1和JNK表达的影响

Effect of curcumin on learning-memory ability and expression of HMGB1 and JNK in rat model of Alzheimer disease

目的:探讨姜黄素对阿尔茨海默病(AD)大鼠学习记忆能力、海马高迁移率族框蛋白1(HMGB1)及c-Jun氨基末端激酶(JNK)表达的影响。方法:36只雄性SD大鼠随机分为4组:空白对照组(A组)、AD模型组(B组,鹅膏覃氨酸Meynert基底核注射)、AD模型+姜黄素治疗组(C组,腹腔注射100 mg·kg-1·d-1持续6 d)和AD模型+溶剂对照组(D组,腹腔注射4 mL/kg玉米油持续6 d)。Morris水迷宫测试大鼠平均逃避潜伏期(AEL),免疫组化和Western blotting法检测海马HMGB1和JNK的表达。结果:与A组相比,B和D组大鼠造模后各时点AEL明显延长(P<0.05),C组大鼠第5天和第6天AEL较B组相应时点明显缩短(P<0.05);B组和D组海马存在HMGB1大量胞浆、胞外释放情况(P<0.05),而C组海马区HMGB1胞浆、胞外释放无明显差异(P>0.05)。4组大鼠海马总HMGB1表达水平比较差异无统计学意义(P>0.05),但B组和D组海马JNK表达水平增高(P<0.05)。结论:姜黄素能够改善AD大鼠的学习记忆能力,其机制可能与抑制HMGB1的胞浆、胞外释放及JNK的表达下调有关。

AIM：To evaluate the effect of curcumin on impaired learning-memory ability and the expression of high mobility group box protein 1 （ HMGB1 ） and c-Jun N-terminal kinase （ JNK ） in a rat model of Alzheimer disease （AD）.METHODS：Male Sprague-Dawley rats, weighing 250-270 g, were randomly divided into 4 groups （n=9）：blank control group （group A）, model group （group B）, curcumin treatment group （group C, curcumin injected intraperitoneally at 100 mg· kg^-1· d^-1 for 6 consecutive days） and solvent control group （group D）.The rats of AD model were induced by injection of ibotenic acid into the nucleus basalis of Meynert （ NBM） bilaterally.All rats were trained in Morris maze to assess the ability of learning and memory .The expression of HMGB1 and JNK in the hippocampus was detected by the methods of immunohistochemistry and Western blotting .RESULTS：Compared with group A , the average escape laten-cy （AEL） in groups B and D were obviously longer （P〈0.05）, while AEL in group C in the 5th and 6th days were significantly shorter （P〈0.05）.The releases of HMGB1 in the CA1 and CA3 areas in groups B and D from the nucleus were abundant.Compared with groups B and D , HMGB1 in hippocampal CA1 and CA3 areas in group C secreted out of the nucleus decreased obviously （P〈0.05）.No significant difference of the release of HMGB1 between group A and group C was observed （P〉0.05）.No significant difference in the expression of HMGB1 in the hippocampus among the 4 groups was found （P〉0.05）.However, compared with groups B and D , the expression of JNK in group C was decreased obviously （P〈0.05）.CONCLUSION： Curcumin significantly improves the learning and memory ability of AD rats .The probable mechanisms may be related to inhibiting the release of HMGB 1 from the nucleus of hippocampal neurons and decreasing the expression of JNK in the hippocampus .