CAJ | 학술논문

目的探讨辛伐他汀对脂多糖诱导的帕金森病大鼠模型的保护作用及机制.方法制备偏侧脂多糖诱导帕金森病大鼠模型,随机分成对照组、模型组和辛伐他汀组,每组15只.对照组:黑质区定位注射生理盐水作为假手术对照,术前1h及手术后均腹腔注射与辛伐他汀组等量生理盐水14 d;模型组:于黑质区定位注射LPS,于造模前后均腹腔注射与辛伐他汀组等量生理盐水14 d;治疗组:黑质区定位注射LPS,于造模前后均腹腔注射辛伐他汀(5 mg/kg)14 d.采用行为学观察、免疫组织化学、酶联免疫吸附实验(ELISA)及Western-blot等方法,观察PD模型大鼠的行为学表现、黑质区多巴胺能神经元数量、黑质及纹状体区多巴胺合成限速酶酪氨酸羟化酶(TH)表达水平、黑质致密部抗离子钙结合蛋白1(Iba-1)阳性细胞数量、炎性因子白介素1β(IL-1β)、肿瘤坏死因子α(TNF-α)的表达水平.结果模型组大鼠出现PD典型行为学表现,黑质致密部较对照组显著下降且较未损伤侧减少81.13％ (P＜0.01),同时黑质致密部Iba-1阳性细胞数量、iNOS、IL-1β及TNF-α表达量明显升高(均P＜0.05).经过辛伐他汀治疗处理后大鼠行为表现、Iba-1阳性细胞数量、iNOS、IL-1β及TNF-α的表达量均较模型组明显改善(P＜ 0.05),黑质致密部DA能神经元数量增加并恢复至未损伤侧的60.5％ (P＜0.05).结论辛伐他汀对LPS帕金森病大鼠DA能神经元具有保护效应,机制可能与抑制黑质区神经胶质细胞(星形胶质细胞及小胶质细胞)的激活,发挥抗炎症作用而改善黑质功能有关.
목적 탐토신벌타정대지다당유도적파금삼병대서모형적보호작용급궤제.방법 제비편측지다당유도파금삼병대서모형,수궤분성대조조、모형조화신벌타정조,매조15지.대조조:흑질구정위주사생리염수작위가수술대조,술전1h급수술후균복강주사여신벌타정조등량생리염수14 d;모형조:우흑질구정위주사LPS,우조모전후균복강주사여신벌타정조등량생리염수14 d;치료조:흑질구정위주사LPS,우조모전후균복강주사신벌타정(5 mg/kg)14 d.채용행위학관찰、면역조직화학、매련면역흡부실험(ELISA)급Western-blot등방법,관찰PD모형대서적행위학표현、흑질구다파알능신경원수량、흑질급문상체구다파알합성한속매락안산간화매(TH)표체수평、흑질치밀부항리자개결합단백1(Iba-1)양성세포수량、염성인자백개소1β(IL-1β)、종류배사인자α(TNF-α)적표체수평.결과 모형조대서출현PD전형행위학표현,흑질치밀부교대조조현저하강차교미손상측감소81.13％ (P＜0.01),동시흑질치밀부Iba-1양성세포수량、iNOS、IL-1β급TNF-α표체량명현승고(균P＜0.05).경과신벌타정치료처리후대서행위표현、Iba-1양성세포수량、iNOS、IL-1β급TNF-α적표체량균교모형조명현개선(P＜ 0.05),흑질치밀부DA능신경원수량증가병회복지미손상측적60.5％ (P＜0.05).결론 신벌타정대LPS파금삼병대서DA능신경원구유보호효응,궤제가능여억제흑질구신경효질세포(성형효질세포급소효질세포)적격활,발휘항염증작용이개선흑질공능유관.
Objective To examine the effect of simvastatin treatment on Parkinson's disease rats induced by lipopolysaccharide (LPS) and its mechanism.Methods The LPS-PD model was established by injection of LPS (5 mg/mL) into the right substantia nigra compacta (SNC),and rats were randomly divided into control group,LPS-model group and simvastatin treatment group with 15 rats in each group.Rats in the simvastatin treatment group was intraperitoneally administered simvastatin (5 mg/kg) before,and daily for 14 days after surgery,while the control group and LPS-model group received same volume normal saline and LPS respectively.Ionized calcium binding adaptor molecule 1 (Iba-1)-positive cells and the expression of tyrosine hydroxylase (TH),tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) in the SNC were detected by immunohistochemistry,Western blotting and enzyme-linked immunosorbent assay,respectively.The effect of simvastatin in the PD model was also examined in behavioral tests.Results The LPS-model group exhibited typical animal PD behaviors.Compared with the control group,the LPS-model group exhibited a decreased number of DA neurons,and comparison of the intact side to reduce 81.13％ (P＜0.01) in the SNC,as well as increases in the Iba-1-positive cell number,iNOS,IL-1β and TNF-α expression (P＜0.05).These effects were inhibited by simvastatin treatment (P＜0.05).Conclusion Simvastatin mediates a protective effect on dopaminergic neurons in the SNC in the LPS-PD model,possibly by inhibiting glial cells (astrocytes and microglia) activation,and playing an anti-inflammatory role,thus improving substantia nigra function.