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硫辛酸對(duì)帕金森病大鼠黑質(zhì)線粒體的保護(hù)作用

發(fā)布時(shí)間:2018-05-03 18:09

  本文選題:帕金森病 + -羥基多巴胺 ; 參考:《山東大學(xué)學(xué)報(bào)(醫(yī)學(xué)版)》2017年08期


【摘要】:目的探討帕金森病(PD)大鼠模型中腦線粒體的變化及硫辛酸的保護(hù)作用。方法 80只SD雄性大鼠,隨機(jī)分為假手術(shù)組(20只)、模型組(60只)。將6-羥基多巴胺(6-OHDA)注入大鼠右側(cè)紋狀體建立PD模型,假手術(shù)組注入同等劑量的生理鹽水。建模第4周后運(yùn)用旋轉(zhuǎn)實(shí)驗(yàn)篩選成功模型(40只),隨機(jī)分為PD組(20只)、治療組(20只),治療組給予硫辛酸50 mg/kg·d腹腔注射,連續(xù)14 d,PD組給予同等劑量生理鹽水。治療2周后,Cylinder test分析大鼠運(yùn)動(dòng)能力;化學(xué)發(fā)光法檢測(cè)大鼠右側(cè)中腦黑質(zhì)ATP水平;JC-1法檢測(cè)中腦線粒體膜電位;免疫組化、Western blotting檢測(cè)各組大鼠酪氨酸氫化酶(TH)水平;Western blotting檢測(cè)HSP60的表達(dá)。結(jié)果與假手術(shù)組比較,PD組左側(cè)肢體使用次數(shù)顯著減少(P0.05),中腦ATP水平明顯降低(P0.05),膜電位顯著降低(P0.05),TH表達(dá)水平顯著降低(P0.05),HSP60表達(dá)水平無(wú)明顯變化(P0.05);硫辛酸治療后,治療組左側(cè)肢體使用次數(shù)顯著上升(P0.05),ATP水平顯著升高(P0.05),膜電位顯著升高(P0.05),TH表達(dá)水平顯著增高(P0.05),HSP60表達(dá)水平略微降低,但無(wú)統(tǒng)計(jì)學(xué)意義(P0.05)。結(jié)論 PD大鼠黑質(zhì)線粒體功能降低但線粒體數(shù)量無(wú)明顯改變,硫辛酸可顯著改善PD癥狀及線粒體功能。
[Abstract]:Objective to investigate the changes of cerebral mitochondria and the protective effect of lipoic acid in Parkinson's disease (PD) rat model. Methods 80 SD male rats were randomly divided into sham operation group (n = 20) and model group (n = 60). The PD model was established by injecting 6-hydroxydopamine 6-OHDAs into the right striatum of rats, and the sham operation group was injected with the same dose of normal saline. After 4 weeks of modeling, 40 successful models were selected by rotating experiment, and were randomly divided into PD group (n = 20) and treatment group (n = 20). The treatment group was intraperitoneally injected with lipoic acid for 50 mg/kg d and the PD group was given the same dose of normal saline for 14 days. After 2 weeks of treatment, the motor ability of rats was determined by Cylinder test, the ATP level in the right midbrain of rats was detected by chemiluminescence assay and the mitochondrial membrane potential of mesencephalon was detected by JC-1 method. The expression of HSP60 was detected by Western blotting at the level of tyrosine hydrogenase (THH). Results compared with the sham-operated group, the number of left limb use in PD group was significantly reduced, the level of ATP in midbrain was significantly decreased, the level of membrane potential was significantly decreased, and the expression level of HSP60 was significantly decreased in PD group, while the expression level of HSP60 in P0.05 was not significantly changed after lipoic acid treatment. In the treatment group, the frequency of use of the left limb was significantly increased and the level of P0.05 + ATP was significantly increased. The membrane potential was significantly increased and the expression of P0.05TH was significantly increased. The expression level of HSP60 was slightly decreased, but there was no significant difference between the two groups. Conclusion the mitochondrial function of substantia nigra in PD rats was decreased, but the number of mitochondria was not changed. Lipoic acid could significantly improve the symptoms and mitochondrial function of PD.
【作者單位】: 貴州醫(yī)科大學(xué)人體解剖學(xué)教研室;貴州醫(yī)科大學(xué)生物學(xué)教研室;貴州醫(yī)科大學(xué)附屬醫(yī)院神經(jīng)內(nèi)科;貴州醫(yī)科大學(xué)附屬醫(yī)院兒科;
【基金】:貴州省科技廳聯(lián)合基金(黔科合LG字[2012]021,黔科合LH字[2014]7077) 貴州省化學(xué)合成藥物研發(fā)利用工程技術(shù)研究中心(黔科合[2016]平臺(tái)人才5402) 貴州省普通高等學(xué)校藥物化學(xué)工程研究中心(黔教合KY字[2014]219號(hào))
【分類號(hào)】:R742.5

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