Ahmed Hh, Salem Am, Atta Hm, Ghazy Ma, Aglan Ha
Department of Hormones, Medical Research Division, National Research Centre, Cairo, Egypt
Department of Biochemistry, Faculty of Science, Ain Shams University, Cairo, Egypt.
Hum Exp Toxicol. 2014 Dec;33(12):1217-31. doi: 10.1177/0960327114524238. Epub 2014 Feb 24.
Parkinson's disease (PD) is a common neurodegenerative disorder in middle-aged and elderly people. This study aimed to elucidate the role of mesenchymal stem cells (MSCs) in management of PD in ovariectomized rat model. MSCs were excised from adipose tissue of both the omentum and the inguinal fat pad of male rats, grown, and propagated in culture; then characterized morphologically; and by the detection of surface markers gene expression. In this study, 40 ovariectomized animals were classified into 5 groups; group 1 was ovariectomized control, groups 2 to 5 were subcutaneously administered with rotenone for 14 days after 1 month of ovariectomy for induction of PD. Group 2 was left untreated; groups 3, 4, and 5 were treated with Sinemet(®), Cerebrolysin(®), and a single dose of adipose tissue-derived MSCs (ADMSCs), respectively. Y-chromosome gene (sry) was assessed by polymerase chain reaction (PCR) in brain tissue of the female rats. Serum transforming growth factor β (TGF-β), monocyte chemoattractant protein 1 (MCP-1), and brain-derived neurotrophic factor (BDNF) levels were assayed using enzyme-linked immunosorbent assay technique. Brain dopamine level was assayed fluorometrically, while brain tyrosine hydroxylase (TH) gene expression was detected by semiquantitative real-time PCR. The PD group showed significant increase in serum TGF-β and MCP-1 levels associated with significant decrease in serum BDNF, brain dopamine, and brain TH gene expression levels. In contrast, all treatments produce significant decrease in serum TGF-β and MCP-1 levels in concomitant with significant increase in serum BDNF, brain dopamine, and brain TH gene expression levels. In conclusion, the observed improvements in the studied biomarkers due to ADMSCs infusion might be attributed to their immunomodulatory, anti-inflammatory, and neurotrophic effects.
帕金森病(PD)是中老年人常见的神经退行性疾病。本研究旨在阐明间充质干细胞(MSCs)在去卵巢大鼠帕金森病模型治疗中的作用。从雄性大鼠的网膜和腹股沟脂肪垫的脂肪组织中分离出MSCs,进行培养、生长和增殖;然后进行形态学鉴定,并检测表面标志物基因表达。本研究将40只去卵巢动物分为5组;第1组为去卵巢对照组,第2至5组在去卵巢1个月后皮下注射鱼藤酮14天以诱导帕金森病。第2组不进行治疗;第3、4和5组分别用息宁(®)、脑蛋白水解物(®)和单剂量脂肪组织来源的间充质干细胞(ADMSCs)进行治疗。通过聚合酶链反应(PCR)评估雌性大鼠脑组织中的Y染色体基因(sry)。采用酶联免疫吸附测定技术检测血清转化生长因子β(TGF-β)、单核细胞趋化蛋白1(MCP-1)和脑源性神经营养因子(BDNF)水平。用荧光法检测脑多巴胺水平,用半定量实时PCR检测脑酪氨酸羟化酶(TH)基因表达。帕金森病组血清TGF-β和MCP-1水平显著升高,同时血清BDNF、脑多巴胺和脑TH基因表达水平显著降低。相比之下,所有治疗均使血清TGF-β和MCP-1水平显著降低,同时血清BDNF、脑多巴胺和脑TH基因表达水平显著升高。总之,输注ADMSCs后所观察到的研究生物标志物的改善可能归因于其免疫调节、抗炎和神经营养作用。