论文部分内容阅读
目的:研究抑郁模型大鼠海马组织中内质网应激调控因子的表达及β-细辛醚的干预作用,并探讨其相关的作用机制。方法:建立慢性轻度不可预见性应激刺激(CUMS)大鼠模型,将100只大鼠随机分为5组,分别为正常组,模型组,氟西汀组(10 mg·kg-1),β-细辛醚低剂量组(25 mg·kg-1)和高剂量组(50 mg·kg-1),每组20只,从造模第8天开始每天灌胃1次给药,连续21 d。于实验的第0天和第29天进行旷场实验;采用Nissl染色法观察各组大鼠海马组织神经元尼氏体的变化;实时荧光定量PCR(Real-time PCR)技术检测各组大鼠海马组织蛋白激酶R样内质网激酶(PERK),CCAAT/增强子结合蛋白同源蛋白(CHOP),钙网蛋白(CRT)mRNA表达情况;蛋白质免疫印迹(Western blot)技术检测各组大鼠海马组织PERK,CHOP,CRT蛋白表达。结果:经28 d慢性不可预见性温和刺激后,模型组大鼠与正常组大鼠比较,水平运动和垂直运动得分明显减少(P<0.05);β-细辛醚低、高剂量组和氟西汀组大鼠与模型组比较,水平运动和垂直运动得分明显增加(P<0.05)。尼氏染色结果显示,模型组大鼠海马组织神经元细胞浆着色变浅,尼氏小体颗粒明显减少;β-细辛醚低、高剂量组大鼠海马区神经元形态相对较好,尼氏小体颗粒较模型组增多。模型组与正常组大鼠比较,PERK,CHOP,CRT mRNA表达上调(P<0.05),与模型组比较,β-细辛醚低、高剂量组和氟西汀组中PERK,CHOP,CRT mRNA表达明显下调(P<0.05)。与正常组比较,模型组大鼠PERK,CHOP,CRT蛋白表达均明显升高(P<0.05);与模型组大鼠比较,氟西汀组、β-细辛醚低、高剂量组PERK,CHOP,CRT蛋白表达明显减少(P<0.05)。结论:β-细辛醚可能是通过调节海马内质网功能发挥抗抑郁作用。
OBJECTIVE: To investigate the expression of ER stress-regulating factors in hippocampus of rats with depression model and the effect of β-asarone on the mechanism of action. Methods: A rat model of chronic mild unpredictable stress stimulation (CUMS) was established. 100 rats were randomly divided into 5 groups: normal group, model group, fluoxetine group (10 mg · kg -1) , low dose β-asarone group (25 mg · kg -1) and high dose group (50 mg · kg -1), 20 rats in each group. For 21 days. Open field experiments were carried out on day 0 and day 29 of the experiment. Nissl staining was used to observe the changes of Nissl bodies in hippocampus of rats in each group. Real-time PCR (Real-time PCR) PERK, CHOP and CRT mRNA in hippocampus of rats were detected by Western blotting. Western blot was used to detect the expression of CHOP, Hippocampal tissue PERK, CHOP, CRT protein expression. Results: After 28 days of chronic unpredictable mild stimulation, the scores of horizontal motion and vertical motion in model group were significantly lower than those in normal group (P <0.05) Compared with the model group, the scores of horizontal motion and vertical motion of Xetin group increased significantly (P <0.05). Nissl staining showed that the hippocampal neurons in the model group had a lighter staining in the cytoplasm of the hippocampal neurons and a significant decrease in Nissl microsomal particles. Neurons in hippocampus of rats in the low-dose and high-dose β-asarone groups showed relatively good morphology, Small body particles more than the model group. The expression of PERK, CHOP and CRT mRNA in model group was significantly higher than that in normal group (P <0.05). Compared with model group, PERK, CHOP and CRT mRNA in low, high dose and fluoxetine groups The expression was significantly down-regulated (P <0.05). Compared with the normal group, the expression of PERK, CHOP and CRT in the model group was significantly increased (P <0.05). Compared with the model group, PERK, CHOP, CRT protein expression was significantly reduced (P <0.05). Conclusion: β-asarone may play an antidepressant effect by regulating the function of endoplasmic reticulum in the hippocampus.