雷公藤甲素对DSP4致大鼠蓝斑NE能神经元丢失及海马NE能神经纤维溃变的影响

为了观察雷公藤甲素(T10)对DSP4致成年SD大鼠蓝斑去甲肾上腺素能(NE)神经元丢失及海马NE能神经纤维溃变的保护作用,将24只大鼠随机分为实验组(DSP4组)、治疗组(DSP4+T10组)、对照组(NS组)。DSP4组、DSP4+T10组动物在第1d、30d腹腔内注射DSP4(25μg/kg),NS组动物同时间腹腔内注射等容量生理盐水。DSP4+T10组动物第1d开始用T10[10μg/(kg.d)]灌胃持续45d,DSP4组、NS组动物用等容量生理盐水灌胃。45d后取材,用酪氨酸羟化酶(TH)多克隆抗体免疫组织化学染色显示蓝斑NE能神经元和海马NE能神经纤维,双盲法计数蓝斑去甲肾上腺素能神经元细胞数,HPIAS高清晰度彩色病理图像测量系统测定海马CA3区神经纤维阳性表达产物的平均灰度值。结果显示:NS组海马NE纤维长而连续;DSP4组海马NE纤维少,断裂现象多见,DSP4+T10组纤维的连续性较DSP4组好;DSP4组蓝斑NE阳性细胞数(505个±24个)明显低于NS组(1069个±49个)和DSP4+T10组(996个±63个)(P<0.05)。DSP4组海马NE阳性神经纤维平均灰度值为(141.89±2.17),明显高于NS组(134.32±2.29)和DSP4+T10组(136.59±3.25)(P<0.05)。以上实验结果提示:DSP4对大鼠蓝斑NE能神经元及海马NE能神经纤维有损伤,雷公藤甲素对其有保护作用。

Effects of triptolide on the neuronal loss in the locus coeruleus and NE fibers degeneration in the hippocampus of adult rat induced by DSP4

To investigate the protective roles of triptolide(T10)on the norepinephrine(NE)neuronal loss in locus coeruleus and the NE fibers degeneration in hippocampus of adult SD rat induced by DSP4,24 SD rats were randomly divided into DSP4 group,DSP4+T10 group and NS group.Rats in DSP4 and DSP4+T10 group were injected intraperitoneally DSP4(25 μg/kg)on the day 1 and day 30.The rats in the NS group were injected intraperitoneally the equal volume of the normal saline.Then the rats in group DSP4+T10 were administrated intragastricly T10[10 μg/(kg·d)] for 45 days from the 1st day,the rats in group NS and DSP4 were given the same volume of the normal saline.The rats were sacrificed and the brain removed after 45 d treatment.Tyrosine hydroxylase(TH)immunohistochemical staining was used to show NE neurons in the locus coeruleus(LC)and NE nerve fibers in the hippocampus.Double blind methods to count the neuronal numbers in the LC,and gray value of TH fibers in the hippocampus were required by MedHPIAS pathologic imaging-analysis system.The results showed that the NE fibers in the hippocampus of group NS was longer and continuous,while in group DSP4 was fewer and inconsecutive,and the continuity of NE nerve fibers in the group DSP4+T10 was much better than that of DSP4 group.The number of TH-positive neuron in the LC of group DSP4(505±24)was lower than that of group NS(1069±49)and group DSP4+T10(996±63)(P<0.05).The mean grey volume of NE nerve fiber in hippocampus of group DSP4(141.89±2.17)was higher than that of group NS(134.32±2.29)and group DSP4+T10(136.59±3.25)(P<0.05).These results indicate that T10 possess of neuronal protective roles for the NE neuronal loss in LC and the NE fibers degeneration in hippocampus induced by DSP4.