Objective: To observe the effect of electroacupuncture (EA) on the cognitive impairment and expressions of inositol-dependent kinase 1α (IRE1α)/c-Jun N-terminal kinase (JNK) pathway-related proteins in diabetic mice, so as to explore its underlying mechanism.
Methods: Thirty db/db mice were randomly divided into model group (n=15) and EA group (n=15), and 15 db/m mice were chosen as the control group. EA was applied to "Baihui" (GV20) and "Shenting" (GV24), bilateral "Pishu" (BL20) and "Shenshu" (BL23), "Zusanli" (ST36) and "Sanyinjiao" (SP6) for 20 min, and bilateral "Feishu" (BL13), "Hegu" (LI4) and "Taichong" (LR3) were stimulated with filiform needles, with the needles retained for 20 min, once daily, 6 days a week for 4 weeks. The daily food intake, water intake, and weekly body weight and blood glucose of the mice in each group were recorded. The learning and memory abilities were detected by Morris water maze, the morphology of hippocampal cells was observed by HE staining, and IRE1α-JNK pathway-related proteins IRE1α, JNK, anti-apoptotic protein (Bcl-2) were detected by Western blot.
Results: Compared with the control group, the food intake, water intake, body weight, blood glucose in the mo-del group were significantly increased (P<0.01), the escape latency was significantly prolonged (P<0.05), the times of cros-sing platform were significantly reduced (P<0.01), and the expression levels of IRE1α and JNK proteins were significantly increased (P<0.01), while the expression of Bcl-2 protein was significantly decreased (P<0.01). Compared with the model group, the food and water intake in the EA group were significantly decreased (P<0.01), the body weight and blood glucose were significantly decreased (P<0.05, P<0.01), the escape latency was significantly shortened (P<0.05), the times of crossing platform significantly increased (P<0.05), and the expression levels of IRE1α and JNK proteins were significantly decreased (P<0.05), while the Bcl-2 expression was significantly increased (P<0.01). The cells in hippocampal CA1 area of mice in the model group are in disorder, with unclear nuclei and obvious vacuoles; while the morphology of nerve cells in EA group was significantly improved.
Conclusion: EA can improve the cognitive impairment of db/db mice, as well as regulate body weight, blood glucose, and improve the cell morphology in the hippocampus, which may be related to its function in regulating the IRE1α-JNK pathway and related proteins.
目的：观察电针对糖尿病模型小鼠认知障碍及肌醇依赖酶1α(IRE1α)-c-Jun氨基末端激酶（JNK）通路相关蛋白的影响，探讨其作用机制。方法：经Morris水迷宫实验筛选出30只成模的db/db小鼠，随机分为电针组与模型组，每组15只，15只db/m小鼠作为空白组。电针组针刺双侧“肺俞”“脾俞”“肾俞”“合谷”“后三里”“三阴交”“太冲”及“百会”“神庭”，“百会”“神庭”连接1对电极，同侧的“脾俞”“肾俞”连接1对电极，“三阴交”“后三里”连接1对电极，20 min/次，1次/d，干预6 d，休息1 d，连续治疗4周。记录各组小鼠每天摄食量、饮水量及每周的体质量、血糖；Morris水迷宫实验检测小鼠学习及记忆能力；HE染色法观察小鼠海马CA1区细胞形态；Western blot法检测小鼠海马IRE1α、JNK、B淋巴细胞瘤2(Bcl-2)蛋白表达水平。结果：与空白组比较，模型组精神萎靡、反应迟钝，摄食量、饮水量明显增多(P<0.01)，体质量、血糖明显升高(P<0.01)，逃避潜伏期明显延长(P<0.05)，穿越原平台次数明显减少(P<0.01)，海马CA1区细胞排列混乱，细胞核不清，空泡现象明显，海马组织中IRE1α、JNK蛋白表达水平明显升高(P<0.01)，Bcl-2蛋白表达水平明显降低(P<0.01)。与模型组比较，电针组反应灵敏、活泼好动，摄食量、摄水量明显减少(P<0.01)，体质量、血糖明显降低(P<0.05，P<0.01)，逃避潜伏期缩短(P<0.05)，穿越原平台次数增多(P<0.05)，海马CA1区细胞形态改善明显，海马组织中IRE1α、JNK蛋白表达水平明显降低(P<0.05)，Bcl-2蛋白表达水平明显升高(P<0.01)。结论：电针可改善db/db小鼠认知障碍，调节体质量、血糖，改善海马组织细胞形态，其机制可能是通过调节IRE1α-JNK通路及相关蛋白来实现的。.
Keywords: IRE1α-JNK pathway; Cognitive impairment; Diabetes; Electroacupuncture; db/db mice.