Wu Su-Hui, Shi Ya-Jin, An Ying-Feng, Zhao Dan-Dan, Li Han-Bing, Li Gen-Lin
Henan University of Chinese Medicine, Henan Zhong-jing Recipe Health and Aging Industry Engineering Research Center Zhengzhou 450046, China.
Zhongguo Zhong Yao Za Zhi. 2022 Dec;47(23):6485-6493. doi: 10.19540/j.cnki.cjcmm.20220721.702.
This paper aims to explore the neuroprotective effect of cinnamaldehyde(CA) in mice with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)-induced subacute Parkinson's disease(PD) and the mechanism. To be specific, male C57 BL/6 mice(n=72, SPF) were randomized into control group, model group, positive control(madopar 0.1 mg·g(-1)) group, and low-dose, me-dium-dose, and high-dose CA groups(0.15, 0.30, 0.60 mg·g(-1)). MPTP(intraperitoneal injection, 0.03 mg·g(-1), once a day for 5 days) was used to induce subacute PD in mice except for the control group. The administration began from the day of modeling and lasted 19 days. On the 0 th, 12 th, and 19 th day, the open field test, pole test, and rotarod test were carried out. After the tests, the mice were killed and brains were separated. In addition, the organ index was measured. The number of cells in substantia nigra(SN) in the midbrain of MPTP-induced PD model mice was detected based on hematoxylin and eosin(HE) staining. The levels of tyrosine hydroxylase(TH)-and α-synuclein(α-Syn)-positive cells in SN were determined by immunohistochemical staining, and the protein levels of TH and α-Syn in SN by Western blot. The results showed that the MPTP-stimulated mice had abnormal behaviors such as erect hair, arched back, rigidity of the tail, slow movement, and tremor, decreased number of crossings and rearing, increased frequency of urination and defecation, longer time of pole climbing, and shorter time of staying on the rotating rod. In addition, the mice showed obvious damage of neurons in the SN and reduced neuron cells in irregular arrangement with some shrinking. In addition, the average optical density of TH in SN decreased and that of α-Syn increased. All these suggested the successful modeling. CA displayed obvious therapeutic effect on the PD mice, as manifested by the increased number of crossings and rearing, decreased frequency of urination and defecation, shorter time of climbing pole, longer time of staying on the rotating rod, and more neuron cells in the SN with a few pykno-tic cells. Moreover, CA significantly alleviated the decrease of TH and the overexpression of α-Syn in SN. As a result, the MPTP-induced injury of dopaminergic neurons was alleviated. The performance of 0.3 mg·g(-1) CA was the best. This study is expected to lay a scientific basis for the development of CA products.
本文旨在探讨肉桂醛(CA)对1-甲基-4-苯基-1,2,3,6-四氢吡啶(MPTP)诱导的亚急性帕金森病(PD)小鼠的神经保护作用及其机制。具体而言,将雄性C57 BL/6小鼠(n = 72,无特定病原体级)随机分为对照组、模型组、阳性对照组(美多芭0.1 mg·g⁻¹)以及低剂量、中剂量和高剂量CA组(0.15、0.30、0.60 mg·g⁻¹)。除对照组外,采用MPTP(腹腔注射,0.03 mg·g⁻¹,每天1次,共5天)诱导小鼠亚急性PD。给药从建模当天开始,持续19天。在第0、12和19天,进行旷场试验、杆试验和转棒试验。试验结束后,处死小鼠并分离脑组织。此外,测量器官指数。基于苏木精-伊红(HE)染色检测MPTP诱导的PD模型小鼠中脑黑质(SN)的细胞数量。通过免疫组织化学染色测定SN中酪氨酸羟化酶(TH)和α-突触核蛋白(α-Syn)阳性细胞的水平,通过蛋白质免疫印迹法测定SN中TH和α-Syn的蛋白水平。结果显示,MPTP刺激的小鼠出现竖毛、弓背、尾巴僵硬、运动迟缓、震颤等异常行为,穿越次数和直立次数减少,排尿和排便频率增加,爬杆时间延长,在转棒上停留时间缩短。此外,小鼠SN中的神经元出现明显损伤,神经元细胞数量减少,排列不规则且部分萎缩。此外,SN中TH的平均光密度降低,α-Syn的平均光密度升高。所有这些表明建模成功。CA对PD小鼠显示出明显的治疗作用,表现为穿越次数和直立次数增加,排尿和排便频率降低,爬杆时间缩短,在转棒上停留时间延长,SN中的神经元细胞增多且有少量固缩细胞。此外,CA显著减轻了SN中TH的降低和α-Syn的过表达。结果,MPTP诱导的多巴胺能神经元损伤得到缓解。0.3 mg·g⁻¹ CA的效果最佳。本研究有望为CA产品的开发奠定科学基础。