抑郁症大鼠海马CA1区及齿状回毛细血管的体视学研究

Stereological study of capillaries in CA1 of hippocampus and dentate gyrus in depression model rats

目的:研究慢性不可预见性刺激(chronically unpredicted stress,CUS)所致抑郁症模型大鼠海马CA1区和齿状回(dentate gyrus,DG)体积及毛细血管的改变。方法:选取Sprague Dawley(SD)大鼠,经筛选后随机分为对照组10只和模型组10只。模型组采取慢性不可预见刺激建立抑郁症模型,共给予应激35 d,对照组不给予应激。利用糖水偏好实验和开场实验检测模型是否建立成功。建模成功后,分别从模型组和对照组中各随机选取5只SD大鼠,运用体视学和免疫组化染色相结合的方法对大鼠海马CA1区和DG毛细血管进行定量研究,剩余5只进行相关分子生物学研究。结果:模型组大鼠和对照组大鼠在体质量[(314.81±31.52)g,(349.18±28.23)g,t=2.569,P=0.019]、糖水偏好实验[(82.37±8.44)%,(89.33±3.97)%,t=2.359,P=0.03]、开场实验结果[(48.30±39.49)分,(87.70±38.32)分,u=-1.988,P=0.047]具有统计学差异,模型组较对照组大鼠海马总体积[(88.84±7.51)mm3,(99.89±12.55)mm3,t=2.388,P=0.028]、海马CA1区[(27.78±1.84)mm3,(32.38±3.69)mm3,t=3.522,P=0.004]和DG[(21.02±2.61)mm3,(24.20±3.33)mm3,t=2.377,P=0.029]体积明显减少,模型组较对照组大鼠海马CA1区毛细血管总长度[(8.454±1.010)m,(11.012±1.642)m,t=2.967,P=0.018]、总体积[(0.104±0.019)mm3,(0.151±0.021)mm3,t=3.720,P=0.006]、总表面积[(1.025±0.113)cm2,(1.589±0.313)cm2,t=3.794,P=0.013]、平均直径[(3.884±0.458)μm,(4.580±0.419)μm,t=2.509,P=0.036]下降以及DG毛细血管的总体积[(0.078±0.021)mm3,(0.117±0.024)mm3,t=2.716,P=0.026]、总表面积[(0.838±0.184)cm2,(1.133±0.074)cm2,t=3.32,P=0.011]、平均直径[(3.611±0.493)μm,(4.630±0.635)μm,t=2.834,P=0.022]下降,结果具有统计学意义。结论:抑郁症模型大鼠大脑海马萎缩,CA1区、DG毛细血管改变,海马结构与毛细血管的改变可能参与了抑郁症的发病机制。

Objective：To investigate the changes of the capillaries in the CA1 of hippocampus and dentate gyrus（DG）in the depression rats induced by chronically unpredicted stress（CUS）. Methods：Male Sprague-Dawley（SD）rats were randomly divided into the control group（n=10）and the model group（n=10）. The depression model was established by giving rats CUS for five weeks. The rats in control group did not receive CUS. The sucrose consumption test and open-field test were used to confirm whether the depression rat model was successfully made. After the depression model of rats was successfully made,5 rats were randomly selected from each group. The immunohistochemistrical technique and the stereological methods were used to quantitatively investigate the capillaries in the CA1 of hippocampus and the DG. The other 5 rats in each group were used for the related molecular biology studies. Results：The rat weight[（314.81±31.52）g,（349.18±28.23）g,t=2.569,P=0.019],the results of the sugar water preference[（82.37±8.44）%,（89.33±3.97）%,t=2.359,P=0.03] and the results of the open-field test[（48.30±39.49）,（87.70±38.32）,u=-1.988,P=0.047] were significantly different between two groups. The volumes of the hippocampus[（88.84±7.51）mm3,（99.89±12.55）mm3,t=2.388,P=0.028],the CA1[（27.78±1.84）mm3,（32.38±3.69）mm3,t=3.522,P=0.004] and the DG[（21.02±2.61）mm3,（24.20±3.33）mm3,t=2.377,P=0.029] in model group were significantly lower than those in the control group. The total length[（8.454 ±1.010） m,（11.012 ±1.642） m,t =2.967,P =0.018],total volume [（0.104 ±0.019）mm3,（0.151 ±0.021） mm3,t =3.720,P =0.006],total surface area[（1.025±0.113）cm2,（1.589±0.313）cm2,t=3.794,P=0.013] and average diameter[（3.884 ±0.458） μm,（4.580±0.419）μm,t=2.509,P=0.036] of the capillaries in the hippocampal CA1 and the total volume[（0.078±0.021）mm,（0.117±0.024）mm,t=2.716,P=0.026],total surface area[（0.838±0.184）,（1.133±0.074）cm2,t=3.32,P=0.011] and average diameter[（3.611 ±0.493） μm,（4.630 ±0.635） μm,t =2.834,P =0.022] of the capillaries in the DG were significantly decreased in model group than in control group. Conclusion：Hippocampal capillary changes can be observed in the CA1 and the DG in depression model rats,which might be involved in the pathogenesis of depression.