摘要
目的确定凋亡蛋白Bcl-2、Bax对甲状腺功能异常引起的认知功能损害大鼠海马的影响。方法健康雌性8周龄清洁级Wistar大鼠30只,随机区组法分为正常对照组、甲状腺功能减低组(甲减组)、甲状腺功能亢进组(甲亢组),每组10只,模型建立成功后利用Morris水迷宫对各组大鼠进行认知功能检测,实验终点取大鼠脑海马组织,行HE染色,使用免疫组化技术检测凋亡蛋白Bcl-2、Bax在大鼠脑内海马神经元表达的变化。结果①各个时间点甲亢组和甲减组的逃避潜伏期时长都要高于正常对照组(F=50.14,P<0.05)。甲亢组、甲减组与正常对照组在目标象限时间的差异具有统计学意义(F=18.571,P<0.05);3组间在目标象限路程的差异有统计学意义(F=17.546,P<0.05);甲亢与甲减组和正常对照组在穿越目标象限次数的差异有统计学意义(Z=17.191,P<0.05)。②海马组织CA1区HE染色:正常对照组海马神经细胞整齐有序,形态紧密、完整,胞内结构层次多而清晰;甲亢组、甲减组海马神经细胞整体结构疏松,细胞数量减少,结构排列不整齐,胞核深染、固缩,核仁消失,胞浆周围发现空晕,胞间距较大。③甲亢组、甲减组Bcl-2、Bax蛋白表达的阳性细胞较正常对照组均增多(F=168.061,P<0.05);甲亢组与甲减组Bcl-2表达差异有统计学意义(F=168.882,P<0.05),而Bax表达差异无统计学意义。结论①甲减、甲亢大鼠的空间学习、记忆能力下降。②甲减、甲亢大鼠海马神经元CA1区Bcl-2、Bax阳性细胞表达数量增加,Bcl-2、Bax比例失调,造成海马神经元发生凋亡,这一过程可能是认知功能出现损害的发病机制之一。
Objective To investigate the relationship between apoptotic protein Bcl-2 and Bax in rat hippocampal neurons and cognitive dysfunction in rats with abnormal thyroid function. Methods Thirty healthy Wistar rats of 8-week-old SPF grade were randomly divided into three groups: (1) Normal control group (n=10);(2) hypothyroidism group (n=10);(3) hyperthyroidism group (n=10) .All rats were sacrificed at the 4th week by heart blood sampling. The serum T3 and T4, TSH were measured. Morris water maze was used to train rats in each group for 6 days. At the end of the experiment, the hippocampus was taken from the rats, and HE staining was performed. The expression of apoptotic protein bcl-2 and Bax in rat hippocampal neurons was detected by immunohistochemistry. Results ① The escape latency of hyperthyroidism and hypothyroidism group was higher than that of the normal group at different time points (P<0.05) . In the test of the target area dwell time, the difference between the hyperthyroid group, the hypothyroid group and the normal group was statistically significant (P<0.05) . In the distance test of the target quadrant, The differences between the three groups were statistically significant (P<0.05) . In the number of passes through the target quadrant, the difference between hyperthyroidism group, hypothyroidism group and normal group was statistically significant (P<0.05) , but there is no significant difference between hyperthyroidism group and hypothyroid group (P>0.05) . ② Hippocampus tissue HE staining: normal control group hippocampal neurons neatly arranged, the shape of the structure was complete and uniform, the nucleus was round or oval, nucleolus obvious, chromatin uniform level and more clear, nucleus round or oval, obviously, hyperthyroidism group, hypothyroidism group of neuronal structure loose, the number decreased, arranged disorder, deep nuclear staining, shrinkage, nucleolus disappeared, cytoplasm around the empty halo, cell spacing larger. ③The positive cells expressing Bcl-2 and Bax protein in the hyperthyroidism group and the hypothyroidism group were increased compared with the normal control group (P<0.05) . Compareds with hyperthyroidism group, the expression of Bcl-2 positive cells was increased in hypothyroidism (P<0.05) . Conclusions ① The spatial learning and memory abilities of the rats with hypothyroidism and the hyperthyroid are lower than those in the normal control group.②The number of apoptotic protein positive cells in Bcl-2 and Bax neurons of hippocampus in rats with hypothyroidism and hyperthyroid increased, and the proportion of Bcl-2 and Bax was impaired,which indicates that apoptosis occurred in hippocampal neurons. This process may be one of the pathogenesis of cognitive impairment.
作者
张强
杨蕴天
金山
张培人
塔拉
乌云图
白银宝
Zhang Qiang;Yang Yuntian;Jin Shan;Zhang Peiren;Ta La;Wu Yun- tu;Bai Yinbao(Department of Neurology, Affiliated Hospital of Inner Mongolia Medical College, Hohhot 010059, China;Department of Thyroid Surgery, Affiliated Hospital of Inner Mongolia Medical College, Hohhot 010059, China)
出处
《中华内分泌外科杂志》
CAS
2018年第6期492-496,共5页
Chinese Journal of Endocrine Surgery
基金
国家自然科学基金(81460157)
内蒙古自治区“草原英才”工程项目.
作者简介
通信作者:杨蕴天,Email:yangyuntian@sina.com.
