何首乌提取物二苯乙烯苷对血管性痴呆模型大鼠内质网应激相关蛋白的影响

Effect of tetrahydroxystilbene glucoside from Polygonum multiflorum on endoplasmic reticulum stress related proteins in vascular dementia model rats

关键词:  何首乌  二苯乙烯苷  血管性痴呆  内质网应激

Key words:  Polygonum multiflorum  tetrahydroxystilbene glucoside  vascular dementia  endoplasmic reticulum stress

摘要:

[目的] 研究何首乌提取物二苯乙烯苷对血管性痴呆模型大鼠海马组织中内质网应激相关蛋白表达的影响。[方法] SD大鼠经Morris水迷宫筛选后，采用改良的双侧颈总动脉阻断法制备血管性痴呆大鼠模型。随机分为假手术组（Sham组）、模型组（Model组）和何首乌提取物二苯乙烯苷（TSG）干预组，采用Morris水迷宫进行行为检测；苏木精-伊红（HE）染色观察海马组织病理变化；免疫组化（IHC）法染色检测凋亡相关蛋白表达；蛋白免疫印迹（Western Blot）法检测大鼠海马组织中内质网应激相关蛋白的表达。[结果] TSG干预组可明显提高大鼠的学习记忆能力（P<0.05），显著改善大鼠海马区病理表现，降低大鼠海马组织中半胱氨酸天冬氨酸蛋白酶-3（Caspase-3）、B淋巴细胞瘤-2（Bcl-2）相关X蛋白（Bax）、葡萄糖调节蛋白78（GRP78）、转录因子CCAAT/增强子结合蛋白（C/EBP）同源蛋白（CHOP）、磷酸化蛋白激酶R样内质网激酶（p-PERK）、磷酸化真核细胞起始因子2α（p-eIF2α）和激活转录因子4（ATF4）蛋白表达（P<0.05），提高Bcl-2蛋白表达（P<0.05）。[结论] 内质网应激参与了血管性痴呆的发生发展过程，何首乌提取物二苯乙烯苷可能通过调控内质网应激相关蛋白表达，抑制神经细胞凋亡，从而改善血管性痴呆大鼠学习记忆障碍。

Abstract:

[Objective] To study the effect of tetrahydroxystilbene glucoside(TSG) from Polygonum multiflorumon the expression of endoplasmic reticulum stress(ERS) related proteins in hippocampus of rats with vascular dementia.[Methods] SD rats were screened by Morris water maze, then these animals were established vascular dementia(VD) by the improved bilateral common carotid artery occlusion(BCCAO) method. They were randomly divided into Sham group, Model group and TSG intervention group. Morris water maze was used for behavior detection. The pathological changes of hippocampus were observed by HE staining. The expression of apoptosis-related proteins were detected by immunohistochemistry. The expression of endoplasmic reticulum stress-related proteins in rats hippocampus were detected by Western Blot.[Results] TSG intervention groups could significantly improve the learning and memory ability of rats(P<0.05). The pathological manifestations of hippocampus of rats were significantly improved. Decreased the protein expressions of Caspase-3, Bax, GRP78, CHOP, p-PERK, p-ELF2α and ATF4 in rats hippocampus (P<0.05), and increased the protein expression of Bcl-2(P<0.05).[Conclusion] ERS is involved in the occurrence and development of VD, and TSG from Polygonum multiflorummay improve learning and memory impairment in VD rats by regulating the expression of ERS-related proteins and inhibiting the apoptosis of nerve cells.