姜黄素对神经病理性痛大鼠脊髓背角及背根神经节神经元大麻素受体1和NR2B表达的影响

目的 探讨姜黄素对神经病理性痛大鼠脊髓背角及背根神经节(DRG)神经元大麻素受体1 (CBR1)及含NR2B亚基N-甲基-D-天冬氨酸(NMDA)受体表达的影响.方法 雄性SD大鼠72只,体重200～230 g,采用随机数字表法,将其随机分为4组(n=18):假手术组(S组)、慢性压迫性损伤组(CCI组)、姜黄素组(Cur组)和溶媒对照组(SC组).S组仅分离、暴露坐骨神经,其余3组采用慢性压迫性损伤法制备神经病理性痛模型.Cur组术后腹腔注射姜黄素100 mg·kg-1·d-1,连续14 d,SC组给予等容量二甲基亚砜.分别于术前2d、术后1、3、7、10、14 d时测定机械缩足反应阈值(MWT)和热缩足潜伏期(TWL).分别于术后3、7、14 d时处死6只大鼠,取脊髓背角和DRG,采用免疫组化法检测神经元CBR1和NR2B的表达.结果 与S组比较,其他3组术后MWT降低,TWL缩短,脊髓背角和DRG神经元CBR1和NR2B表达上调(P＜0.05);与CCI组比较,Cur组术后MWT升高,TWL延长,脊髓背角和DRG神经元CBR1表达上调,NR2B表达下调(P＜0.05),SC组上述指标差异无统计学意义(P＞0.05).结论 姜黄素可减轻大鼠神经病理性痛,其机制与脊髓背角及DRG神经元CBR1表达上调、NR2B表达下调有关.     

姜黄素对自发性高血压大鼠脑缺血再灌注时海马神经元凋亡及c-Jun氨基末端激酶3和突触后密度蛋白95表达的影响

目的 探讨姜黄素对自发性高血压(SH)大鼠脑缺血再灌注时海马神经元凋亡及c-Jun 氨基末端激酶3(JNK3)和突触后密度蛋白95(PSD95)表达的影响.方法 与雄性WKY同源的SH大鼠135只和雄性WKY大鼠90只,清洁级,体重275～325 g,采用随机数字表法,将WKY大鼠随机分为2组(n=45):假手术组(W-S组)及脑缺血再灌注组(W-I/R组),将SH大鼠随机分为3组(n=45):假手术组(S-S组)和脑缺血再灌注组(S-I/R组)及姜黄素组(S-C组).采用四血管阻断法制备全脑缺血再灌注模型.W-S组和S-S组仅分离双侧颈总动脉,W-I/R组和S-I/R组于再灌注30 min时腹腔注射玉米油10 ml/kg,S-C组于再灌注30 min时腹腔注射姜黄素100 mg/kg.于再灌注2 h,6 h、1 d、3 d和7d时进行海马凋亡神经元计数,并测定海马JNK3和PSD95蛋白的表达水平.结果 与W-S组比较,S-S组海马凋亡神经元计数增加(P<0.05),JNK3蛋白表达差异无统计学意义(P>0.05);与S-S组比较,S-I/R组海马凋亡神经元计数增加,JNK3蛋白表达上调(P<0.05);与S-I/R组比较,S-C组海马凋亡神经元计数减少,JNK3蛋白表达下调(P<0.05).各组海马PSD95蛋白表达比较差异无统计学意义(P>0.05).结论 姜黄素可抑制SH大鼠脑缺血再灌注时神经元凋亡,其机制与下调海马JNK3蛋白表达有关,姜黄素下调海马JNK3蛋白表达可能与PSD95途径无关.

Abstract：

Objective To investigate the effect of curcumin on apoptosis in hippocampal neurons and the expression of c-Jun N-terminal kinase 3 (JNK3) and postsynaptic density protein 95 (PSD95) in hippocampus during cerebral ischemia-reperfusion (I/R) in rats with spontaneous hypertension (SH) .Methods One hundred and thirty-five male rats (homologous with WKY) with SH and 90 male normotensive WKY rats, weighing 275-325 g,were used in this study. The WKY rats were randomized into 2 groups ( n = 45 each) : sham operation group (WS group) and cerebral I/R group (W-I/R group) . The rats with SH were randomly divided into 3 groups ( n = 45each) : sham operation group (S-S group), cerebral I/R group (S-I/R group) and curcumin group (S-C group) .Global cerebral ischemia was produced by 4 vessel-occlusion method. The bilateral common carotid arteries were only exposed but not ligated in W-S and S-S groups. Intraperitoneal corn oil 10 ml/kg was injected at 30 min of reperfusion in W-I/R and S-I/R groups. Intraperitoneal curcumin 100 mg/kg was injected at 30 min of reperfusion in S-C group. Three animals in each group were sacrificed at 2 h, 6 h, 1 d, 3 d and 7 d of reperfusion and their brains were harvested for determination of apoptosis in hippocampal neurons and the expression of JNK3 and PSD95in hippocampus. Results The number of apoptotic neurons was significantly increased in S-S group compared with W-S group ( P < 0.05) . The number of apoptotic neurons was significantly increased and the expression of JNK3was up-regulated in S-I/R group compared with S-S group ( P < 0.05) . The number of apoptotic neurons was significantly decreased and the expression of JNK3 was down-regulated in S-C group compared with S-I/R group (P <0.05) . There was no significant difference in the expression of PSD95 among all the groups ( P > 0.05) . Conclusion Curcumin can inhibit apoptosis in hippocampal neurons and the mechanism is related to down-regulation of the expression of JNK3 in hippocampus. The mechanism by which curcumin down-regulates the expression of JNK3in hippocampus may not be related to PSD95 pathway.     

姜黄素对自发性高血压大鼠脑缺血再灌注时海马神经元凋亡及c-Jun氨基末端激酶3和突触后密度蛋白95表达的影响

目的 探讨姜黄素对自发性高血压(SH)大鼠脑缺血再灌注时海马神经元凋亡及c-Jun 氨基末端激酶3(JNK3)和突触后密度蛋白95(PSD95)表达的影响.方法 与雄性WKY同源的SH大鼠135只和雄性WKY大鼠90只,清洁级,体重275～325 g,采用随机数字表法,将WKY大鼠随机分为2组(n=45):假手术组(W-S组)及脑缺血再灌注组(W-I/R组),将SH大鼠随机分为3组(n=45):假手术组(S-S组)和脑缺血再灌注组(S-I/R组)及姜黄素组(S-C组).采用四血管阻断法制备全脑缺血再灌注模型.W-S组和S-S组仅分离双侧颈总动脉,W-I/R组和S-I/R组于再灌注30 min时腹腔注射玉米油10 ml/kg,S-C组于再灌注30 min时腹腔注射姜黄素100 mg/kg.于再灌注2 h,6 h、1 d、3 d和7d时进行海马凋亡神经元计数,并测定海马JNK3和PSD95蛋白的表达水平.结果 与W-S组比较,S-S组海马凋亡神经元计数增加(P<0.05),JNK3蛋白表达差异无统计学意义(P>0.05);与S-S组比较,S-I/R组海马凋亡神经元计数增加,JNK3蛋白表达上调(P<0.05);与S-I/R组比较,S-C组海马凋亡神经元计数减少,JNK3蛋白表达下调(P<0.05).各组海马PSD95蛋白表达比较差异无统计学意义(P>0.05).结论 姜黄素可抑制SH大鼠脑缺血再灌注时神经元凋亡,其机制与下调海马JNK3蛋白表达有关,姜黄素下调海马JNK3蛋白表达可能与PSD95途径无关.     

姜黄素对自发性高血压大鼠脑缺血再灌注时海马神经元凋亡及c-Jun氨基末端激酶3和突触后密度蛋白95表达的影响

目的 探讨姜黄素对自发性高血压(SH)大鼠脑缺血再灌注时海马神经元凋亡及c-Jun 氨基末端激酶3(JNK3)和突触后密度蛋白95(PSD95)表达的影响.方法 与雄性WKY同源的SH大鼠135只和雄性WKY大鼠90只,清洁级,体重275～325 g,采用随机数字表法,将WKY大鼠随机分为2组(n=45):假手术组(W-S组)及脑缺血再灌注组(W-I/R组),将SH大鼠随机分为3组(n=45):假手术组(S-S组)和脑缺血再灌注组(S-I/R组)及姜黄素组(S-C组).采用四血管阻断法制备全脑缺血再灌注模型.W-S组和S-S组仅分离双侧颈总动脉,W-I/R组和S-I/R组于再灌注30 min时腹腔注射玉米油10 ml/kg,S-C组于再灌注30 min时腹腔注射姜黄素100 mg/kg.于再灌注2 h,6 h、1 d、3 d和7d时进行海马凋亡神经元计数,并测定海马JNK3和PSD95蛋白的表达水平.结果 与W-S组比较,S-S组海马凋亡神经元计数增加(P<0.05),JNK3蛋白表达差异无统计学意义(P>0.05);与S-S组比较,S-I/R组海马凋亡神经元计数增加,JNK3蛋白表达上调(P<0.05);与S-I/R组比较,S-C组海马凋亡神经元计数减少,JNK3蛋白表达下调(P<0.05).各组海马PSD95蛋白表达比较差异无统计学意义(P>0.05).结论 姜黄素可抑制SH大鼠脑缺血再灌注时神经元凋亡,其机制与下调海马JNK3蛋白表达有关,姜黄素下调海马JNK3蛋白表达可能与PSD95途径无关.