《環(huán)丙沙星對腦脊液氨基酸神經(jīng)遞質(zhì)含量影響的研究》由會(huì)員分享,可在線閱讀,更多相關(guān)《環(huán)丙沙星對腦脊液氨基酸神經(jīng)遞質(zhì)含量影響的研究(2頁珍藏版)》請?jiān)谘b配圖網(wǎng)上搜索。
1、環(huán)丙沙星對腦脊液氨基酸神經(jīng)遞質(zhì)含量影響的研究
目的觀察靜滴環(huán)丙沙星(CPLX)后患者CSF中抑制性氨基酸(GABA、Gly)和興奮性氨基酸(Asp、Glu)含量的變化,探討 CPLX致癇的發(fā)生機(jī)制。方法患者靜脈滴注CPLX 200mg/次,給藥后60min記錄腦電圖,于用藥前作脊髓穿刺,抽取CSF作為對照,用藥后120min時(shí)抽取CSF作為試驗(yàn)樣本,用高效液相色譜法測定CSF中氨基酸的含量。結(jié)果靜滴CPLX后可引起患者CSF中抑制性氨基酸和興奮性氨基酸的含量發(fā)生明顯的變化。用藥后120min時(shí),CSF中GABA含量為2.150.88μmol/L,明顯高于用藥前的0.62
2、0.18μmol/L(P
氨基酸神經(jīng)遞質(zhì);腦脊液;高效液相色譜;環(huán)丙沙星 Study on the changes of concentration of amino acids neurotransmitter in the CSF induced by ciprofloxacin
ObjectiveTo evaluate the changes of concentration of inhibitory and excitatory amino acids neurotransmitter (Asp, Glu, GABA, Gly) in the CSF after
3、 intravenous drip ciprofloxacin (CPLX), and conduct an investigation into the pathogenic mechanism of epilepsy induced by CPLX. MethodsThe intravenous drip ciprofloxacin 200mg.time-1 to volunteers, before dosage, the CSF of volunteers was taken out as control, electroencephalogram (EEG) was recorded
4、 at 60 min after dosage, then the CSF of volunteers was taken out again at 120min after administration as experimental samples, and the amino acids were detected with high performance liquid chromatography.ResultsThe concentration of inhibitory and excitatory amino acids in the CSF was obviously cha
5、nged after dosage. At 120min after administration, the concentration of GABA(2.150.88μmol/L) was significantly higher than before dosage (0.620.18μmol/L, P
amino acid;neurotransmitter; cerebrospinal fluid;high performance liquid chromatography; ciprofloxacin
文獻(xiàn)報(bào)道,氟喹諾酮類藥物(FQs)的致癇機(jī)制是阻止GABA與神經(jīng)細(xì)
6、胞相應(yīng)的受體結(jié)合,而致腦神經(jīng)細(xì)胞的興奮抑制調(diào)節(jié)失調(diào) [1,2]。靜滴環(huán)丙沙星易引起神經(jīng)系統(tǒng)不良反應(yīng),嚴(yán)重者可引起癲癇大發(fā)作[3]。氨基酸是重要的神經(jīng)遞質(zhì)之一,在中樞神經(jīng)的興奮和抑制過程中起著重要的作用。筆者研究發(fā)現(xiàn)靜注環(huán)丙沙星(CPLX)后可引起大鼠腦脊液(CSF)中興奮性和抑制性氨基酸神經(jīng)遞質(zhì)含量發(fā)生明顯的改變[4],環(huán)丙沙星在臨床治療中引起的神經(jīng)系統(tǒng)不良反應(yīng)機(jī)制未見詳細(xì)的文獻(xiàn)報(bào)道。選擇用CPLX進(jìn)行抗感染治療的患者,觀察腦脊液(cerebrospinal fluid, CSF)中興奮性氨基酸天門冬氨酸(aspartic acid,Asp)、谷氨酸(glutamic acid,Glu)和抑制
7、性氨基酸γ-氨基丁酸(γ-aminobutyric acid,GABA)、甘氨酸(glycine,Gly)等氨基酸神經(jīng)遞質(zhì)含量的變化,探討CPLX引起神經(jīng)系統(tǒng)不良反應(yīng)的發(fā)生機(jī)制。
1材料與方法
1.1對象用環(huán)丙沙星進(jìn)行抗感染治療的臨床病例志愿者,男12例,女8例,年齡18~60歲。
1.2試劑與儀器環(huán)丙沙星由天津藥研院太原制藥廠提供。日本光電7314F型腦電圖儀、美國Backman 6300型黃金系列高效液相氨基酸分析儀和JY-10型真空低溫凍干機(jī)。
1.3病例處理給臨床感染病例志愿者靜脈滴注環(huán)丙沙星200mg/次,用藥后60min記錄腦
8、電變化情況,記錄時(shí)間20min,按照國際10-20系統(tǒng)電極安置法安放頭皮電極,做單極導(dǎo)聯(lián)和雙極導(dǎo)聯(lián)描記,并做睜閉眼、過度換氣和閃光誘發(fā)等試驗(yàn)。以黃遠(yuǎn)桂標(biāo)準(zhǔn)進(jìn)行診斷[5]。用藥前抽取患者腦脊液作為對照,用藥后120min抽取腦脊液作試驗(yàn)組,分別進(jìn)行高效液相分析法測定CSF中的興奮性氨基酸谷氨酸(Glu)、天門冬氨酸(Asp)和抑制性氨基酸γ-氨基丁酸(GABA)、甘氨酸(Gly)等4種氨基酸的含量。
1.4氨基酸分析CSF 200μl加100g/L磺柳酸30μl,混勻使蛋白析出,然后用微孔濾膜離心管10000g離心除去蛋白。去蛋白液放-80℃真空冰凍干燥機(jī)內(nèi)凍干,再加pH2.3枸櫞酸鋰緩沖液100μl充分混合溶解后備用。處理好的樣本用6300型氨基酸自動(dòng)分析儀,作高效液相色譜(high performance liquid chromatography, HPLC)分析,測定CSF中的谷氨酸、天門冬氨酸、γ-氨基丁酸和甘氨酸的含量。用配對t檢驗(yàn)對實(shí)驗(yàn)數(shù)據(jù)進(jìn)行統(tǒng)計(jì)分析,結(jié)果以xs表示。