灵芝酸A对抑郁症大鼠神经胶质细胞功能障碍及海马细胞凋亡信号的影响

Effects of Ganoderic acid A on neuroglial cell dysfunction and hippocampal cell apoptosis in depressed rats

目的探讨灵芝酸A对抑郁大鼠的治疗作用,及其可能的作用机制。方法将大鼠随机分为对照组(正常饲养)、模型组(慢性不可预知性温和刺激法构建抑郁模型)、低剂量组(抑郁模型+10 mg·kg^(-1)灵芝酸A)、高剂量组(抑郁模型+20 mg·kg^(-1)灵芝酸A)和阳性组(抑郁模型+2.1 mg·kg^(-1)盐酸氟西汀),每组10只。药物处理结束后,检测大鼠抑郁样行为,用酶联免疫吸附试验法检测血清神经递质及细胞因子的表达水平,用蛋白质印迹法检测海马组织相关蛋白的表达水平,用原位末端转移酶标记法(Tunel)实验法检测海马组织的凋亡情况。结果对照组、模型组、低剂量组、高剂量组和阳性组的蔗糖偏好度分别为(80.88±6.20)%、(60.40±8.61)%、(68.70±5.90)%、(76.32±2.79)%和(80.08±5.64)%,游泳静止时间分别为(117.60±6.26)、(188.40±19.49)、(169.80±17.54)、(152.40±15.84)和(136.00±7.31)s,5-羟色胺(5-HT)水平分别为(24.13±1.65)、(9.70±0.89)、(13.93±1.68)、(17.95±1.36)和(15.09±1.39)ng·mL^(-1),白细胞介素(IL)-6水平分别为(9.20±1.05)、(64.90±5.95)、(44.19±4.23)、(30.16±2.91)和(52.81±7.73)pg·mL^(-1),整合素AM亚基(CD11b)蛋白相对表达水平分别为0.42±0.06、1.03±0.14、0.73±0.09、0.57±0.04和0.99±0.14,胶质纤维酸性蛋白(GFAP)相对表达水平分别为0.77±0.09、0.43±0.03、0.59±0.09、0.73±0.07和0.46±0.03,细胞凋亡率分别为(3.53±0.27)%、(23.11±1.73)%、(18.18±1.98)%、(12.08±1.97)%和(15.91±0.94)%。模型组的上述指标与对照组比较,阳性组和低、高剂量组的上述指标与模型组比较,在统计学上差异均有统计学意义(均P<0.05)。结论灵芝酸A可以通过调节胶质神经细胞功能,抑制神经炎性和凋亡减少大鼠抑郁样行为。

Objective To investigate the therapeutic effect of Ganoderic acid A on depressed rats and its possible mechanism.Methods Rats were randomly divided into control group(normal feeding),model group(chronic unpredictability mild stimulation method to build depression model),low-dose group(depression model+10 mg·kg^(-1)ganoderic acid A),high-dose group(depression model+20 mg·kg^(-1)ganoderic acid A),positive group(depression model+2.1 mg·kg^(-1)fluoxetine hydrochloride),each group consisted of 10 animals.The sugar water preference test and the forced swimming test measured depression-like behavior in rats.The expression of neurotransmitters and cytokines was detected by enzyme-linked immunosorbent assay;Western blot assay was used to detect the expression of related proteins in hippocampus;the apoptosis of hippocampus was detected by TdT mediated dUDP nick end labeling(Tunel)assay.Results The sugar water preference rates of rats in control group,model group,low-dose group,high-dose group and positive group were(80.88±6.20)%,(60.40±8.61)%,(68.70±5.90)%,(76.32±2.79)%and(80.08±5.64)%,respectively;the stationary time was(117.60±6.26),(188.40±19.49),(169.80±17.54),(152.40±15.84)and(136.00±7.31)s,respectively;5-hydroxytryptamine(5-HT)levels were(24.13±1.65),(9.70±0.89),(13.93±1.68),(17.95±1.36)and(15.09±1.39)ng·mL^(-1),respectively;the levels of IL-6 were(9.20±1.05),(64.90±5.95),(44.19±4.23),(30.16±2.91)and(52.81±7.73)pg·mL^(-1),respectively;the relative expression levels of CD11b were 0.42±0.06,1.03±0.14,0.73±0.09,0.57±0.04 and 0.99±0.14,respectively;the relative expression levels of glial fibrillary acidic protein(GFAP)were 0.77±0.09,0.43±0.03,0.59±0.09,0.73±0.07 and 0.46±0.03,respectively;the apoptosis rates were(3.53±0.27)%,(23.11±1.73)%,(18.18±1.98)%,(12.08±1.97)%and(15.91±0.94)%,respectively.Compared with the control group,the above indexes in the positive group and the low-and high-dose groups were significantly different from those in the model group(all P<0.05).Conclusion Ganoderma A can reduce depression-like behavior in rats,inhibiting neuritis and apoptosis by regulating the function of glial nerve cells.