牛磺酸对锰致大鼠海马组织毒性损害的干预机理研究
摘要
目的：通过体内动物实验方法,探讨牛磺酸对锰致大鼠海马组织神经毒性损害的干预机理。
方法：取SPF级SD雄性大鼠适应性饲养一周后,将其分为：A：24w对照组：腹腔注射0.9%NaCl溶液,共24w。B：24w治疗组：腹腔注射MnCl2·4H2O 15mg.kg-1／d,连续12w,再给予牛磺酸200mg／kg,每周3次,连续12w。C：12w染锰组：MnCl2·4H2O 15mg.kg-1／d,腹腔注射,连续12w。D：12w对照组：腹腔注射0.9%NaCl溶液,连续12w。E：12w预防组：染锰剂量和方法与染锰组一致；牛磺酸添加剂量为200mg／kg,腹腔注射,与染锰同时进行,每周3次,连续12w。各组实验动物终止注射后,随即开始Morris水迷宫实验(MWM),为期1w。终止实验后,即处死大鼠,分离大鼠海马组织,对以下指标进行检测：电镜观察海马组织中细胞凋亡、细胞器的改变及其超微结构；ROS试剂盒对线粒体活性氧簇进行测定；分别用WB、RT-PCR从蛋白、基因层面检测Bcl-2家族(Bcl-2,Bax,Bcl-xl,Bak),凋亡诱导因子AIF以及ChAT在海马组织中的表达情况。
结果：①MWM显示：逃避潜伏期整体呈下降趋势。C组明显长于E组(P<0.05),B组与A组无差别。但A组和B组要高于D组和E组(P<0.05)。②锰能诱导大鼠海马的神经元的凋亡和造成细胞器的损伤,牛磺酸可以拮抗锰的神经毒性,改善上述损伤。③牛磺酸预防和治疗能有效地下调锰刺激后引起的线粒体活性氧的升高。④锰能上调Bax、Bak、AIF表达,下调Bcl-2、Bcl-xl表达,牛磺酸预防比染锰后再给予牛磺酸治疗能更有效地保护海马组织,抑制锰对凋亡因子的这种诱导作用。但部分凋亡因子的蛋白印迹测定结果和RT-PCR结果未能完全吻合,有待进一步分析。⑤锰能够引起ChAT蛋白表达量的降低,牛磺酸能拮抗锰的这一作用。
结论：锰可能通过氧化应激、诱导细胞淍亡导致神经损伤,通过抑制Ach的合成来降低胆碱能神经元的突触兴奋性传递,最终导致大鼠学习记忆功能障碍。牛磺酸通过抗氧化、调控凋亡因子和增强ChAT的表达来拮抗锰的毒性作用。
Objective:To study the effect of taurine on manganese chloride neuroto-xicity in rat's hippocampus in vivo.
Methods:SD rats were divided into five groups after one week of observation:A:24w normal control, the group animals received daily of intraperitoneal(ip.) injections of sterile saline for 24 weeks. B:24w Tau treated group:First, rats were received ip. injection of MnCl2·4H2O 15mg.kg-1/d once a day for 12 weeks, then the rats received Tau 200mg/kg three times per week for 12 weeks. C:12w Mn treated group:rats were recievd the daily injection of Mn as Tau treated group for 12 weeks. D:12w normal control group:rats were received ip. injection of sterile saline as group A for 12 weeks. E:Tau preventive group:The Mn level of this group are the same as Mn's, the tau level are the same as group B,three times per week, the assayes remained for 12 weeks. At the end of the experiment, a period of 1 week morris water maze test(MWM) began immediately. End of the test, that is, the rats were killed, isolated rat hippocampus, were detected on the following indicators:electron microscopy of apoptosis in hippocampus, changes in organelles and ultrastructure; ROS kit on mitochondrial reactive oxygen species were measured; respectively WB, RT-PCR from the protein level of detection of Bcl-2 gene family (Bcl-2, Bax, Bcl-xl, Bak), apoptosis inducing factor AIF and ChAT in the hippocampus of the expression.
Results:①MWM Show:escape latency of the overall downward trend. C group was significantly longer than E group (P<0.05), B group and A group of non-discrimination. But the A group and B group was higher than D group and E group (P<0.05).②manganese can induce the apoptosis of hippocampal neurons and cause damage to organelles, taurine could antagonize the neurotoxicity of manganese to improve the injury.③prevention and treatment of taurine reduced manganese can effectively stimulated mitochondrial reactive oxygen species increased.④manganese can raise Bax, Bak, AIF expression, reduced Bcl-2, Bcl-xl expression, and then exposed to manganese compared with taurine to taurine treatment to more effectively protect the hippocampus, inhibition of apoptosis factors in manganese this induction. However, some apoptotic factors by western blot and RT-PCR determination of the results not fully consistent with the results, pending further analysis.⑤ChAT manganese can cause reduced protein expression, taurine can attenuate the effects of manganese.
Conclusion:Manganese may be through oxidative stress, induced apoptosis leads to nerve damage, by inhibiting the synthesis of Ach to reduce cholinergic neurons in excitatory synaptic transmission, the end result of learning and memory dysfunction.Taurine by oxidation, regulation of apoptotic factors and enhance the expression of antagonistic ChAT manganese toxicity.
方法：取SPF级SD雄性大鼠适应性饲养一周后,将其分为：A：24w对照组：腹腔注射0.9%NaCl溶液,共24w。B：24w治疗组：腹腔注射MnCl2·4H2O 15mg.kg-1／d,连续12w,再给予牛磺酸200mg／kg,每周3次,连续12w。C：12w染锰组：MnCl2·4H2O 15mg.kg-1／d,腹腔注射,连续12w。D：12w对照组：腹腔注射0.9%NaCl溶液,连续12w。E：12w预防组：染锰剂量和方法与染锰组一致；牛磺酸添加剂量为200mg／kg,腹腔注射,与染锰同时进行,每周3次,连续12w。各组实验动物终止注射后,随即开始Morris水迷宫实验(MWM),为期1w。终止实验后,即处死大鼠,分离大鼠海马组织,对以下指标进行检测：电镜观察海马组织中细胞凋亡、细胞器的改变及其超微结构；ROS试剂盒对线粒体活性氧簇进行测定；分别用WB、RT-PCR从蛋白、基因层面检测Bcl-2家族(Bcl-2,Bax,Bcl-xl,Bak),凋亡诱导因子AIF以及ChAT在海马组织中的表达情况。
结果：①MWM显示：逃避潜伏期整体呈下降趋势。C组明显长于E组(P<0.05),B组与A组无差别。但A组和B组要高于D组和E组(P<0.05)。②锰能诱导大鼠海马的神经元的凋亡和造成细胞器的损伤,牛磺酸可以拮抗锰的神经毒性,改善上述损伤。③牛磺酸预防和治疗能有效地下调锰刺激后引起的线粒体活性氧的升高。④锰能上调Bax、Bak、AIF表达,下调Bcl-2、Bcl-xl表达,牛磺酸预防比染锰后再给予牛磺酸治疗能更有效地保护海马组织,抑制锰对凋亡因子的这种诱导作用。但部分凋亡因子的蛋白印迹测定结果和RT-PCR结果未能完全吻合,有待进一步分析。⑤锰能够引起ChAT蛋白表达量的降低,牛磺酸能拮抗锰的这一作用。
结论：锰可能通过氧化应激、诱导细胞淍亡导致神经损伤,通过抑制Ach的合成来降低胆碱能神经元的突触兴奋性传递,最终导致大鼠学习记忆功能障碍。牛磺酸通过抗氧化、调控凋亡因子和增强ChAT的表达来拮抗锰的毒性作用。
Objective:To study the effect of taurine on manganese chloride neuroto-xicity in rat's hippocampus in vivo.
Methods:SD rats were divided into five groups after one week of observation:A:24w normal control, the group animals received daily of intraperitoneal(ip.) injections of sterile saline for 24 weeks. B:24w Tau treated group:First, rats were received ip. injection of MnCl2·4H2O 15mg.kg-1/d once a day for 12 weeks, then the rats received Tau 200mg/kg three times per week for 12 weeks. C:12w Mn treated group:rats were recievd the daily injection of Mn as Tau treated group for 12 weeks. D:12w normal control group:rats were received ip. injection of sterile saline as group A for 12 weeks. E:Tau preventive group:The Mn level of this group are the same as Mn's, the tau level are the same as group B,three times per week, the assayes remained for 12 weeks. At the end of the experiment, a period of 1 week morris water maze test(MWM) began immediately. End of the test, that is, the rats were killed, isolated rat hippocampus, were detected on the following indicators:electron microscopy of apoptosis in hippocampus, changes in organelles and ultrastructure; ROS kit on mitochondrial reactive oxygen species were measured; respectively WB, RT-PCR from the protein level of detection of Bcl-2 gene family (Bcl-2, Bax, Bcl-xl, Bak), apoptosis inducing factor AIF and ChAT in the hippocampus of the expression.
Results:①MWM Show:escape latency of the overall downward trend. C group was significantly longer than E group (P<0.05), B group and A group of non-discrimination. But the A group and B group was higher than D group and E group (P<0.05).②manganese can induce the apoptosis of hippocampal neurons and cause damage to organelles, taurine could antagonize the neurotoxicity of manganese to improve the injury.③prevention and treatment of taurine reduced manganese can effectively stimulated mitochondrial reactive oxygen species increased.④manganese can raise Bax, Bak, AIF expression, reduced Bcl-2, Bcl-xl expression, and then exposed to manganese compared with taurine to taurine treatment to more effectively protect the hippocampus, inhibition of apoptosis factors in manganese this induction. However, some apoptotic factors by western blot and RT-PCR determination of the results not fully consistent with the results, pending further analysis.⑤ChAT manganese can cause reduced protein expression, taurine can attenuate the effects of manganese.
Conclusion:Manganese may be through oxidative stress, induced apoptosis leads to nerve damage, by inhibiting the synthesis of Ach to reduce cholinergic neurons in excitatory synaptic transmission, the end result of learning and memory dysfunction.Taurine by oxidation, regulation of apoptotic factors and enhance the expression of antagonistic ChAT manganese toxicity.
引文
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