[汤剂促进伴抑郁症糖尿病大鼠海马齿状回神经干细胞自我更新并激活Shh信号通路]
[ Decoction promotes neural stem cell self-renewal and activates Shh signaling in the hippocampal dentate gyrus of diabetic rats with depression].
作者信息
Yang H, Wang H, Li C, He X, Lei S, Li W, Meng P, Wang J, Liu J, Wang Y
机构信息
Centre for Medical Innovations, First Affiliated Hospital of Hunan University of Chinese Medicine, Changsha 410007, China.
Centre for Medical Innovations, Science and Technology Innovation Center, Changsha, 410208, China.
出版信息
Nan Fang Yi Ke Da Xue Xue Bao. 2023 May 20;43(5):694-701. doi: 10.12122/j.issn.1673-4254.2023.05.03.
OBJECTIVE
To investigate the effect of Decoction (ZJJ) on Shh signaling and self-renewal of neural stem cells in the hippocampal dentate gyrus of diabetic rats with depression.
METHODS
Diabetic rat models with depression were randomly divided into model group, positive drug (metformin + fluoxetine) group, and low-, medium-, and high-dose ZJJ groups (=16), with normal SD rats as the control group. The positive drugs and ZJJ were administered by gavage, and the rats in the control and model groups were given distilled water. After the treatment, blood glucose level was detected using test strips, and behavioral changes of the rats were assessed by forced swimming test and water maze test. ELISA was used to examine the serum level of leptin; The expressions of nestin and Brdu proteins in the dentate gyrus of the rats were detected using immunofluorescence assay, and the expressions of self-renewal marker proteins and Shh signaling proteins were detected using Western blotting.
RESULTS
The diabetic rats with depression showed significantly increased levels of blood glucose and leptin ( < 0.01) and prolonged immobility time in forced swimming test ( < 0.01) and increased stage climbing time with reduced stage seeking time and stage crossings in water maze test ( < 0.01). The expressions of nestin and Brdu in the dentate gyrus, the expressions of cyclin D1, SOX2, Shh, Ptch1, Smo in the hippocampus and the nuclear expression of Gli-1 were decreased ( < 0.01) while hippocampal Gli-3 expression was increased significantly ( < 0.01) in the rat models. Treatment of rat models with high-dose ZJJ significantly reduced the blood glucose ( < 0.01) and leptin level ( < 0.05) and improved their performance in behavioral tests ( < 0.01). The treatment also obviously increased the expressions of nestin, Brdu, cyclin D1, SOX2, Shh, Ptch1, and Smo and the nuclear expression of Gli-1 in the dentate gyrus ( < 0.01) and reduced hippocampal expression of Gli-3 ( < 0.05) in the rat models.
CONCLUSION
ZJJ can significantly improve the self-renewal ability of neural stem cells and activate Shh signaling in dentate gyrus of diabetic rats with depression.
目的
探讨止痉散（ZJJ）对糖尿病伴抑郁症大鼠海马齿状回神经干细胞Shh信号通路及自我更新能力的影响。
方法
将糖尿病伴抑郁症大鼠模型随机分为模型组、阳性药物（二甲双胍+氟西汀）组、ZJJ低、中、高剂量组（每组n = 16），以正常SD大鼠作为对照组。阳性药物及ZJJ采用灌胃给药，对照组和模型组大鼠给予蒸馏水。治疗后，用试纸检测血糖水平，通过强迫游泳试验和水迷宫试验评估大鼠的行为变化。采用ELISA法检测血清瘦素水平；用免疫荧光法检测大鼠齿状回中巢蛋白和溴脱氧尿苷蛋白的表达，用蛋白质免疫印迹法检测自我更新标记蛋白和Shh信号蛋白的表达。
结果
糖尿病伴抑郁症大鼠血糖和瘦素水平显著升高（P < 0.01），强迫游泳试验中的不动时间延长（P < 0.01），水迷宫试验中上台攀爬时间增加，寻找平台时间和穿越平台次数减少（P < 0.01）。大鼠模型齿状回中巢蛋白和溴脱氧尿苷的表达、海马中细胞周期蛋白D1、SOX2、Shh、Ptch1、Smo的表达及Gli - 1的核表达均降低（P < 0.01），而海马Gli - 3表达显著增加（P < 0.01）。高剂量ZJJ治疗大鼠模型可显著降低血糖（P < 0.01）和瘦素水平（P < 0.05），并改善其行为学测试表现（P < 0.01）。该治疗还明显增加了大鼠模型齿状回中巢蛋白、溴脱氧尿苷、细胞周期蛋白D1、SOX2、Shh、Ptch1和Smo的表达及Gli - 1的核表达（P < 0.01），并降低了海马中Gli - 3的表达（P < 0.05）。
结论
止痉散可显著提高糖尿病伴抑郁症大鼠齿状回神经干细胞自我更新能力并激活Shh信号通路。
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