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低分子量硫酸软骨素对MPTP致帕金森病模型小鼠多巴胺能神经元的保护作用
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| 篇名： | 低分子量硫酸软骨素对MPTP致帕金森病模型小鼠多巴胺能神经元的保护作用 |
| TITLE： | |
| 摘要： | 目的：观察低分子量硫酸软骨素（CS）对1-甲基-4-苯基-1，2，3，6-四氢吡啶（MPTP）致帕金森病（PD）模型小鼠多巴胺能神经元的保护作用。方法：将C57BL/6小鼠随机分为对照组、MPTP损伤组以及低分子量CS低、高剂量组（100、400 mg/kg）。对照组和MPTP损伤组小鼠均灌胃等容生理盐水，各给药组小鼠均灌胃相应药物，每天1次，连续17 d。自给药后第11天开始，除对照组外，其余各组小鼠均于给药后腹腔注射MPTP溶液（20 mg/kg），每天1次，连续5 d，以复制PD模型。末次给药后，采用转棒式疲劳仪评价小鼠（每组10只）行为学的改变情况，采用免疫组织化学法和免疫荧光法检测小鼠（每组3只）中脑黑质中多巴胺神经元的损伤情况[酪氨酸羟化酶（TH）阳性细胞百分比、荧光强度百分比]，采用高效液相色谱法检测小鼠（每组6只）脑纹状体中多巴胺的含量，采用化学比色法检测小鼠（每组6只）中脑黑质中氧化应激指标[超氧化物歧化酶（SOD）、谷胱甘肽过氧化物酶（GSH-Px）、丙二醛（MDA）]水平。结果：与对照组比较，MPTP损伤组小鼠在转棒上的滞留时间显著缩短，中脑黑质中TH阳性细胞明显减少、荧光强度明显减弱，其阳性细胞百分比和荧光强度百分比，脑纹状体中多巴胺的含量以及中脑黑质中SOD、GSH-Px的活性均显著降低，MDA的含量显著升高（P＜0.01）。与MPTP损伤组比较，低分子量CS各剂量组小鼠在转棒上的滞留时间显著延长，中脑黑质中TH阳性细胞明显增加、荧光强度明显增强，其阳性细胞百分比、荧光强度百分比以及脑纹状体中多巴胺的含量均显著升高，且高剂量组上述指标均显著长于或高于低剂量组（P＜0.05或P＜0.01）；低分子量CS各剂量组小鼠中脑黑质中SOD、GSH-Px的活性均显著升高，低分子量CS高剂量组小鼠中脑黑质中MDA的含量显著降低（P＜0.05或P＜0.01）。结论：预防性给予低分子量CS可剂量依赖性地减轻MPTP致PD模型小鼠中脑黑质中多巴胺能神经元的损伤，增加其脑纹状体中多巴胺的分泌。这种作用可能与抑制脂质过氧化反应、提高组织的抗氧化能力相关。 |
| ABSTRACT： | OBJECTIVE： To observe neuroprotective effects of low-molecular-weight chondroitin sulfate （CS） on dopaminergic neurons in Parkinson’s disease （PD） mice model induced by 1-methyl-4-phenyl-1，2，3，6-tetrahydropyridine （MPTP）. METHODS： C57BL/6 mice were randomly divided into control group， MPTP injury group， low-molecular-weight CS low-dose and high-dose groups （100， 400 mg/kg）. Control group and MPTP injury group were given constant volume of normal saline intragstrically， administration groups were given relevant medicine intragastrically， once a day， for consecutive 17 d. Since 11th day after medication， except for control group， other groups were given MPTP solution （20 mg/kg） intraperitoneally to induce PD model， once a day， consecutive 5 d. After last medication， behavioral changes of mice （10 mice in each group） were evaluated by rotary rod fatigue tester. The damage of dopamine neurons （the percentage of TH positive cell and the percentage of fluorescence intensity） in substantia nigra of mice （3 mice in each group） was detected by immunohistochemistry and immunofluorescence. The content of dopamine in striatum was determined by HPLC （6 mice in each group）. The changes of oxidant stress indexes （SOD， GSH-Px， MDA） in substantia nigra of mice were determined by chemical colorimetry （6 mice in each group）. RESULTS： Compared with control group， retention time of mice on rotating rods was shortened significantly in MPTP injury group； TH positive cells of substantia nigra were decreased significantly， fluorescence intensity was obviously weakened； the percentage of positive cells and fluorescence intensity， the content of dopamine in striatum， the activities of SOD and GSH-Px in substantia nigra were decreased significantly， while the content of MDA was increased significantly （P＜0.01）. Compared with MPTP injury group， retention time of mice on the rotating rods was prolonged significantly in low-molecular-weight CS groups， the number of TH positive cells was increased significantly in substantia nigra and fluorescence intensity was increased significantly； the percentage of positive cells， the percentage of fluorescence intensity and the content of dopamine in striatum were increased significantly， while above indexes of high-dose group were significantly longer or higher than those of low-dose group （P＜0.05 or P＜0.01）. The activities of SOD and GSH-Px in substantia nigra were increased significantly in low-molecular-weight CS groups， while the content of MDA in substantia nigra was decreased significantly in low-molecular-weight CS high-dose group （P＜0.05 or P＜0.01）. CONCLUSIONS： Prophylactic administration of low-molecular-weight CS can relieve the damage of dopaminergic neurons in substantia nigra of PD model mice induced by MPTP in a dose-dependent manner， and increase the secretion of dopamine in striatum. The effect may be related to the inhibition of lipid peroxidation and the enhancement of antioxidant capacity of tissues. |
| 期刊： | 2019年第30卷第8期 |
| 作者： | 高钦，丁红光，孙福生，杨志宏，王井，丁慧婷，高华，鞠传霞 |
| AUTHORS： | GAO Qin，DING Hongguang，SUN Fusheng，YANG Zhihong，WANG Jing，DING Huiting，GAO Hua，JU Chuanxia |
| 关键字： | 低分子量硫酸软骨素；中脑黑质；脑纹状体；多巴胺能神经元；1-甲基-4-苯基-1，2，3，6-四氢吡啶；酪氨酸羟化酶；氧化应激；帕金森病；小鼠 |
| KEYWORDS： | Low-molecular-weight chondroitin sulfate； Substantia nigra； Striatum； Dopaminergic neurons； 1-methyl-4-phenyl- 1，2，3，6-tetrahydropyridine； Tyrosine hydroxylase； Oxidant stress； Parkinson’s disease； Mice |
| 阅读数： | 505 次 |
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