| 张珍珍,位慧芳,张勇,等.海马注射脑源性神经营养因子对大鼠脑卒中后抑郁的作用及机制[J].安徽医药,2023,27(8):1507-1511. |
| 海马注射脑源性神经营养因子对大鼠脑卒中后抑郁的作用及机制 |
| Effect and mechanism of brain-derived neurotrophic factor injected into hippocampus on post-stroke depression in rats |
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| DOI：10.3969/j.issn.1009-6469.2023.08.006 |
| 中文关键词: 脑源性神经营养因子 卒中 抑郁症 脑梗死 环磷酸腺苷 /环磷酸腺苷反应元件结合蛋白 /脑源性神经营养因子信号通路 海马 大鼠 |
| 英文关键词: Brain-derived neurotrophic factor Stroke Depressive disorder Brain infarction cAMP/CREB/BDNF pathway Hippocampus Rats |
| 基金项目:河南省医学科技攻关计划联合共建项目( LHGJ20191045) |
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| 中文摘要: |
| 目的观察海马内注射脑源性神经营养因子( BDNF)对大鼠脑卒中后抑郁的改善作用，并探究其对环磷酸腺苷 /环磷酸腺苷反应元件结合蛋白 /脑源性神经营养因子( cAMP/CREB/BDNF)信号通路的影响。方法 2022年 1―3月选择 SPF级 SD雄性大鼠 95只，采用随机数字表法选择 80只制备脑卒中后抑郁( PSD)模型，余 15只为假手术组。将 PSD造模成功的 64只大鼠采用随机数字表法分为 PSD组、无序干扰组、 BDNF干预组、激活剂组和抑制剂组。造模成功 2h后，给予无序干扰组和 BDNF组大鼠分别注射含无序干扰序列的慢病毒载体和含 BDNF的慢病毒载体，激活剂组和抑制剂组分别给予皮下注射 for skolin和 SQ22536，假手术组和 PSD组注射等量含 5%二甲基亚砜的生理盐水。采用糖水实验和敞箱实验评估大鼠抑郁情况，采用实时荧光定量逆转录 PCR(RT-qPCR)检测各组海马组织 BDNF相对表达水平，苏木精 -伊红( HE)染色观察海马组织病理学变化，测定各组大鼠海马组织去甲肾上腺素( NE)和 5-羟色胺( 5-HT)含量，蛋白质印迹法( Western blotting)检测海马区 cAMP、pCREB、BDNF蛋白表达水平。结果与假手术组比较， PSD组、无序干扰组、 BDNF组糖水消耗量［( 42.69±2.18)%、(42.84±2.29)%、(71.66±3.04)%比( 90.34±3.28)%］、方格穿行次数［(13.72±0.97)次、(13.98±0.75)次、(23.17±1.47)次比( 39.66±1.45)次］和竖起修饰次数［( 9.14±0.45)次、(9.52±0.53)次、(12.96±0.75)次比( 18.65±1.12)次］减少， BDNF相对表达量( 0.62±0.13、0.69±0.09、1.68±0.16比 2.62±0.32)降低，且 BDNF组高于 PSD组和无序干扰组( P<0.05)； HE染色结果显示， PSD组和无序干扰组海马神经元细胞形态相似，数目减少，排列紊乱； BDNF组海马神经元细胞数目增加，排列基本紧密，形态基本规则；假手术组比较， PSD组、无序干扰组、 BDNF组 NE、5-HT水平降低，且 BDNF组高于 PSD组和无序干扰组( P<0.05)。与假手术组与比较， PSD组、无序干扰组、 BDNF组、抑制剂组和激活剂组 cAMP、pCREB、BDNF水平降低，且 BDNF组和激活剂组 >PSD组、无序干扰组和抑制剂组( P<0.05)。结论海马内注射 BDNF对大鼠 PSD症状、海马神经元病理均有改善作用，其作用机制可能与激活 cAMP/CREB/BDNF通路有关。 |
| 英文摘要: |
| Objective To observe the effect of intra-hippocampal injection of BDNF on post-stroke depression in rats, and explore its effect on cAMP/CREB/BDNF signaling pathway.Methods From January to March 2022, 95 male SD rats with SPF grade were se lected and 80 rats were randomly selected to prepare PSD model, and the remaining 15 rats were sham operated.The 64 rats that successfully established the post-stroke depression (PSD) rat model were randomly divided into PSD group, disordered interference group,BDNF group, activator group, and inhibitor group. Two hours after successful modeling, disordered interference group and BDNF groupwere injected with disordered interference sequence-containing lentiviral vector and BDNF-containing lentiviral vector, activator groupand inhibitor group were injected subcutaneously with forskolin and SQ22536, sham operation group and PSD group were injected withequal amounts of 5% dimethyl sulfoxide in saline. Sugar water test and open box test were used to evaluate the depression of rats, andthe relative expression levels of BDNF in hippocampus of each group were detected by RT-qPCR. Hippocampal histopathological changes were observed by HE staining. NE And 5-HT content, Western blot was used to detect the expression levels of cAMP, pCREB, and BDNF proteins in the hippocampus. Results Compared with sham operation group, the consumption of sugar water[(42.69± 2.18)%, (42.84±2.29)%, (71.66±3.04)% vs. (90.34±3.28)%], the number of square passes[(13.72±0.97), (13.98±0.75), (23.17±1.47) vs.(39.66±1.45)] and erect modification[(9.14±0.45), (9.52±0.53), (12.96±0.75) vs. (18.65±1.12)], the relative expression of BDNF is re duced in the PSD group(0.62±0.13, 0.69±0.09, 1.68±0.16 vs. 2.62±0.32), disorder interference group, BDNF group, and BDNF group> PSD group and disorder interference group (P<0.05). The results of HE staining showed that the hippocampal neuron cells of the PSDgroup and the disordered interference group had similar morphology, decreased in number and disordered arrangement; the number ofhippocampal neurons in the BDNF group increased, the arrangement was basically tight, and the morphology was basic. Compared withthe sham operation group, the levels of NE and 5-HT in the PSD group, disordered interference group, and BDNF group decreased, andBDNF group>PSD group and disordered interference group (P<0.05). Compared with sham operation group, camp, pCREB and BDNFlevels in PSD group, disorder interference group, BDNF group, inhibitor group and activator group were decreased, and BDNF groupand activator group were more than PSD group, disorder interference group and inhibitor group(P<0.05).Conclusions Intrahippocampal injection of BDNF can improve the symptoms of PSD and the pathology of hippocampal neurons in rats. The mechanism may be related to the activation of cAMP/CREB/BDNF pathway. |
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