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      紅景天對(duì)帕金森病患者抗氧化及神經(jīng)功能的影響

      2014-09-03 14:08:31董亞賢石紅婷鐘高賢刁芳明
      關(guān)鍵詞:紅景天帕金森病氧化應(yīng)激

      董亞賢+石紅婷+鐘高賢+刁芳明

      【摘要】目的觀察紅景天注射液對(duì)帕金森病(PD)患者的臨床療效及安全性。 方法選擇68例帕金森病患者,隨機(jī)分為對(duì)照組34例、觀察組34例,兩組均常規(guī)抗帕金森治療,而觀察組聯(lián)用紅景天注射液,連續(xù)2周,治療前后行血超氧化物歧化酶(SOD) 和丙二醛(MDA)測(cè)定,并采用H-Y分級(jí)及帕金森病統(tǒng)一評(píng)分量表的第二分量表(UPDRS II)評(píng)定兩組治療前后的臨床療效。 結(jié)果觀察組治療后MDA值低于治療前,而SOD值高于治療前(P<0.05),且治療前后UPDRS II評(píng)分及H-Y分級(jí)比較有明顯改善(P<0.05 ),而對(duì)照組改變不顯著(P>0.05);觀察組與對(duì)照組不良反應(yīng)的比較無明顯統(tǒng)計(jì)學(xué)差異(P>0.05)。結(jié)論紅景天可增強(qiáng)帕金森患者的抗氧化和神經(jīng)功能。

      【關(guān)鍵詞】紅景天;帕金森?。谎趸瘧?yīng)激

      【中圖分類號(hào)】R322.8【文獻(xiàn)標(biāo)識(shí)碼】B

      隨著社會(huì)的老齡化,帕金森氏病(Parkinson's disease,PD)的發(fā)病率逐漸升高,PD作為中老年人常見的中樞神經(jīng)系統(tǒng)退行性疾病,其復(fù)雜的病因和發(fā)病機(jī)制至今尚未闡明,從而延緩PD的發(fā)生發(fā)展是目前研究的重點(diǎn)[1-2] 。目前傾向于認(rèn)為氧化應(yīng)激水平的提高是PD重要的病理生理機(jī)制之一[3-5],且相關(guān)研究證明紅景天具有顯著的抗缺氧、抗疲勞、清除自由基等藥理作用[6]。因此本研究選擇PD為研究對(duì)象,測(cè)定患者的SOD與MDA水平,同時(shí)運(yùn)用UPDRS II評(píng)分及H-Y分級(jí)量表評(píng)估紅景天對(duì)PD患者抗氧化和神經(jīng)功能的作用。

      1資料與方法

      1.1研究對(duì)象

      隨機(jī)連續(xù)性選擇2013年2月~2014年4月我院神經(jīng)內(nèi)科門診和住院的患者。符合原發(fā)性帕金森病的評(píng)定標(biāo)準(zhǔn)[7]患者共68例,女33例,男35例,年齡60-75(69.9±9.5)歲。隨機(jī)分成觀察組34例和對(duì)照組34例,且兩組患者按Hoehn-Yahr分級(jí)[8],分為I級(jí)、II級(jí)、III級(jí)及IV級(jí)。排除標(biāo)準(zhǔn) ①各種原因引起的繼發(fā)性帕金森綜合征及帕金森疊加綜合征;②存在嚴(yán)重的心肝腎功能損害或免疫系統(tǒng)、呼吸系統(tǒng)等疾病;③伴有精神疾病者;④近期行較大手術(shù)或嚴(yán)重外傷者;⑤近1個(gè)月發(fā)生過重大個(gè)人或家庭事件,可能影響患者情緒狀態(tài)者;⑥長(zhǎng)期臥床不起者;⑦語言溝通障礙者。本研究經(jīng)過廣州醫(yī)科大學(xué)附屬第一醫(yī)院倫理委員會(huì)批準(zhǔn),所有患者或其家人均簽署知情同意書。

      1.2方法

      1.2.1一般情況評(píng)估

      入院后仔細(xì)詢問患者一般情況:既往病史、個(gè)人史、家族

      史及患帕金森病的病程;入院后當(dāng)日行CT或MRI檢查排除繼發(fā)性帕金森綜合征及帕金森疊加綜合征,次日空腹采用黃嘌呤氧化酶法測(cè)定SOD及與硫代巴比妥縮合法測(cè)定MDA水平。

      1.2.2治療

      對(duì)入組患者已服用的美多巴、安坦、金剛烷胺等抗帕金森藥物,應(yīng)繼續(xù)服用,并維持原劑量,而對(duì)觀察組患者加用紅景天注射液10 mL加入250m1生理鹽水靜脈滴注,每天一次,連續(xù)2周,治療期間觀察兩組患者的胃腸道反應(yīng)(惡心、嘔吐、食欲減少)、頭痛、頭暈、失眠、精神癥狀、體位性低血壓、開關(guān)現(xiàn)象、劑末現(xiàn)象和晨僵少動(dòng)等。2周后再次測(cè)定兩組的SOD與MDA水平,且采用Hoehn-Yahr:分級(jí)和帕金森病統(tǒng)一評(píng)分量表(Unified Parkinson's Disease Rating Scale,UPDRS)評(píng)分量表的第二分量表(UPDRS II)評(píng)定臨床療效[8,9]。

      1.3統(tǒng)計(jì)學(xué)方法

      采用SPSS 16.0統(tǒng)計(jì)軟件對(duì)數(shù)據(jù)進(jìn)行統(tǒng)計(jì)學(xué)分析,計(jì)數(shù)資料用率表示,組間比較采用 檢驗(yàn),計(jì)量資料用 (±s)表示,兩組間比較采用t檢驗(yàn), P<0.05為差異有統(tǒng)計(jì)學(xué)意義。

      2結(jié)果

      2.1兩組一般資料比較

      觀察組與對(duì)照組比較,年齡、病程、Hochn-Yahr分期等,差異無統(tǒng)計(jì)學(xué)意義(P>0.05,表1)。

      2.3兩組不良反應(yīng)比較

      觀察組與對(duì)照組在不良反應(yīng)比例上比較,差異無統(tǒng)計(jì)學(xué)意義(P>0.05,表3)

      3討論

      紅景天是一種重要的天然植物,被喻為"高原人參"。其主要化學(xué)成分有紅景天苷、酪醇及紅景天多糖,并且含有黃酮類化合物、酚類化合物、蛋白質(zhì)、脂肪、微量揮發(fā)油及微量元素、氨基酸等[10]。研究表明[6,11-12],紅景天本身就具有抗氧化活性,這個(gè)作用是直接地去除自由基繼而保護(hù)機(jī)體減少氧化應(yīng)激的傷害,而非應(yīng)激反應(yīng)的結(jié)果。因此,紅景天的抗氧化及神經(jīng)功能作用逐漸受到關(guān)注。SOD是一種超氧陰離子清除劑,能起到保護(hù)細(xì)胞結(jié)構(gòu)和功能完整的作用,且減少自由基的生成,而MDA是過氧化脂質(zhì)(LPO)的降解產(chǎn)物,MDA含量可以反映LPO的水平,因此這兩種物質(zhì)反映了機(jī)體抗氧化損傷的能力[13-14]。從而本實(shí)驗(yàn)以測(cè)定SOD和MDA水平評(píng)定氧化應(yīng)激含量。

      相關(guān)研究證明[11.12,13],紅景天有典型的"適應(yīng)原樣"作用,這種現(xiàn)象是指該物質(zhì)本身具有微量的毒性,能使機(jī)體產(chǎn)生應(yīng)激反應(yīng),如上調(diào)機(jī)體的抗氧化能力、DNA損傷修復(fù)能力和熱休克蛋白表達(dá)的增加,能使機(jī)體對(duì)隨后的應(yīng)激產(chǎn)生保護(hù)作用。本研究顯示,觀察組,治療后的MDA水平低于治療前,而SOD水平高于治療前,而對(duì)照組治療前后改變不明顯,且治療后兩組比較,觀察組SOD水平升高而MDA水平下降,提示紅景天注射液可能是通過調(diào)節(jié)過氧化反應(yīng)過程,降低MDA的含量和活性,但提高SOD的活性和含量,改善腦細(xì)胞的氧和能量代謝,提高Na+-K+泵ATP酶活性,減少氧自由基生成,使其清除加速,從而減少氧自由基對(duì)神經(jīng)細(xì)胞造成進(jìn)一步損害,具有明顯DA神經(jīng)元保護(hù)作用,可能有助于延長(zhǎng)左旋多巴療效并降低副反應(yīng)。同時(shí)本研究也發(fā)現(xiàn)觀察組,治療后的UPDRS評(píng)分(II)、Hoehn-Yahr:分級(jí)高于治療前,且治療后比較,對(duì)照組的UPDRS評(píng)分(II)、Hoehn-Yahr:分級(jí)高于觀察組,從而預(yù)示,在帕金森病患者中,常規(guī)加用紅景天注射液治療可增強(qiáng)帕金森患者的抗氧化和神經(jīng)功能,延緩帕金森患者的進(jìn)展。

      在治療過程中,本實(shí)驗(yàn)觀察兩組的相關(guān)不良反應(yīng),結(jié)果顯示對(duì)照組發(fā)生率高于觀察組,(26.4%VS20.6%),因此說明紅景天注射液治療帕金森病不良反應(yīng)少,安全性高。由于取材的限制,未能同期檢測(cè)腦脊液相應(yīng)指標(biāo)的變化,另外病人僅限于短期住院觀察,長(zhǎng)期效果如何,均有待進(jìn)一步觀察。

      參考文獻(xiàn)

      [1] Poewe W.Treatments for Parkinson, s disease-past achievements and current clinical needs[J].Neurology,2009,72(7):65-73.

      [2]張宇紅,陳生弟,李江林,等.紅景天甙促進(jìn)帕金森病模型小鼠表達(dá)內(nèi)源性GDNF保護(hù)多巴胺能神經(jīng)元[J].中華神經(jīng)科雜志,2006,39:540.

      [3] Chen WQ,Zhao XL,Hou Y,et al.Protective effects of green tea polyphenols on cognitive impairments induced by psychological stress in rats [J].Behav Brain Res,2009,202(1):71-76.

      [4] Avila I,Reilly MP,Sanabria F,et al.Modeling operant behavior in the Parkinsonian rat[J]. Behav Brain Res,2009,198(2):298-305.

      [5] Sanyal J,Bandyopalnyysk,Baneriee TK,et al.Plasma levels of lipid peroxides in patients with Parkinson, s disease [J].Eur Rev Med Pharmacol Sci,2009,13(2):129-132.

      [6]Sehriner SE,Abrahamyan A,Avanessian A,et a1.Decreased mitochondrial superoxide levels and enhanced protection in against paraquat in Drosophila melanogaster supplemented with Rhodiola roseal[J].Free Radic Res,2009,43(9):836-843.

      [7] 中華醫(yī)學(xué)會(huì)神經(jīng)病學(xué)分會(huì)運(yùn)動(dòng)障礙及帕金森病學(xué)組.帕金森病的診斷[J].中華神經(jīng)科雜志,2006,39(6):169-171.

      [8] Hoehn MM,Yahr MD. Parkinsonism:onset,progression,and mortality[J]. Neurology, 1967, 17:427-442.

      [9] Fahn S,Elton RL.Members of the URDPS Development committee:Unified Parkinson, s disease rating scale [C].In:Fahn S,Marsden CD,Calne DB,Goldstein M,editors.Recentdevelopment in Parkinson, s disease.2 nd ed,F(xiàn)lorham Park,NJ:MacMillan Healthcare Information,1987:153-164.

      [10]金萍.紅景天的研究現(xiàn)狀[J].光明中醫(yī),2011,26(7):1508-1511.

      [11] Wiegant FA,Surinova S,Ytsma E,et al.Plant adaptogens increase lifespan and stress resistance in C.elegans [J].Biogerontology,2009,10(1):27-42.

      [12] Panossian A,Wagner H.Stimulating effect of adaptogens:an overview with parricular reference to their efficaly following single dose administration [J]. Phy tother Res,2005,19(10):819-838.

      [13] Cai L,Wang H,Li Q, et al.Salidroside inhibits H2O2-induced apoptosis in PC12 cells by proventing cytochrome C release and inactivating of caspase cascade [J].Acta Biochim Biophys Sin(shang hai),2008,40(9):796-802.

      [14] Ya S,Chen Y, Liu J, et al.Involvement of ERK1/2 pathway in neuroprotection by salidroside against hydrogen peroxide-induced apoptotic cell death [J].J Mol Neuro Sci,2010,40(3):32-31.

      在治療過程中,本實(shí)驗(yàn)觀察兩組的相關(guān)不良反應(yīng),結(jié)果顯示對(duì)照組發(fā)生率高于觀察組,(26.4%VS20.6%),因此說明紅景天注射液治療帕金森病不良反應(yīng)少,安全性高。由于取材的限制,未能同期檢測(cè)腦脊液相應(yīng)指標(biāo)的變化,另外病人僅限于短期住院觀察,長(zhǎng)期效果如何,均有待進(jìn)一步觀察。

      參考文獻(xiàn)

      [1] Poewe W.Treatments for Parkinson, s disease-past achievements and current clinical needs[J].Neurology,2009,72(7):65-73.

      [2]張宇紅,陳生弟,李江林,等.紅景天甙促進(jìn)帕金森病模型小鼠表達(dá)內(nèi)源性GDNF保護(hù)多巴胺能神經(jīng)元[J].中華神經(jīng)科雜志,2006,39:540.

      [3] Chen WQ,Zhao XL,Hou Y,et al.Protective effects of green tea polyphenols on cognitive impairments induced by psychological stress in rats [J].Behav Brain Res,2009,202(1):71-76.

      [4] Avila I,Reilly MP,Sanabria F,et al.Modeling operant behavior in the Parkinsonian rat[J]. Behav Brain Res,2009,198(2):298-305.

      [5] Sanyal J,Bandyopalnyysk,Baneriee TK,et al.Plasma levels of lipid peroxides in patients with Parkinson, s disease [J].Eur Rev Med Pharmacol Sci,2009,13(2):129-132.

      [6]Sehriner SE,Abrahamyan A,Avanessian A,et a1.Decreased mitochondrial superoxide levels and enhanced protection in against paraquat in Drosophila melanogaster supplemented with Rhodiola roseal[J].Free Radic Res,2009,43(9):836-843.

      [7] 中華醫(yī)學(xué)會(huì)神經(jīng)病學(xué)分會(huì)運(yùn)動(dòng)障礙及帕金森病學(xué)組.帕金森病的診斷[J].中華神經(jīng)科雜志,2006,39(6):169-171.

      [8] Hoehn MM,Yahr MD. Parkinsonism:onset,progression,and mortality[J]. Neurology, 1967, 17:427-442.

      [9] Fahn S,Elton RL.Members of the URDPS Development committee:Unified Parkinson, s disease rating scale [C].In:Fahn S,Marsden CD,Calne DB,Goldstein M,editors.Recentdevelopment in Parkinson, s disease.2 nd ed,F(xiàn)lorham Park,NJ:MacMillan Healthcare Information,1987:153-164.

      [10]金萍.紅景天的研究現(xiàn)狀[J].光明中醫(yī),2011,26(7):1508-1511.

      [11] Wiegant FA,Surinova S,Ytsma E,et al.Plant adaptogens increase lifespan and stress resistance in C.elegans [J].Biogerontology,2009,10(1):27-42.

      [12] Panossian A,Wagner H.Stimulating effect of adaptogens:an overview with parricular reference to their efficaly following single dose administration [J]. Phy tother Res,2005,19(10):819-838.

      [13] Cai L,Wang H,Li Q, et al.Salidroside inhibits H2O2-induced apoptosis in PC12 cells by proventing cytochrome C release and inactivating of caspase cascade [J].Acta Biochim Biophys Sin(shang hai),2008,40(9):796-802.

      [14] Ya S,Chen Y, Liu J, et al.Involvement of ERK1/2 pathway in neuroprotection by salidroside against hydrogen peroxide-induced apoptotic cell death [J].J Mol Neuro Sci,2010,40(3):32-31.

      在治療過程中,本實(shí)驗(yàn)觀察兩組的相關(guān)不良反應(yīng),結(jié)果顯示對(duì)照組發(fā)生率高于觀察組,(26.4%VS20.6%),因此說明紅景天注射液治療帕金森病不良反應(yīng)少,安全性高。由于取材的限制,未能同期檢測(cè)腦脊液相應(yīng)指標(biāo)的變化,另外病人僅限于短期住院觀察,長(zhǎng)期效果如何,均有待進(jìn)一步觀察。

      參考文獻(xiàn)

      [1] Poewe W.Treatments for Parkinson, s disease-past achievements and current clinical needs[J].Neurology,2009,72(7):65-73.

      [2]張宇紅,陳生弟,李江林,等.紅景天甙促進(jìn)帕金森病模型小鼠表達(dá)內(nèi)源性GDNF保護(hù)多巴胺能神經(jīng)元[J].中華神經(jīng)科雜志,2006,39:540.

      [3] Chen WQ,Zhao XL,Hou Y,et al.Protective effects of green tea polyphenols on cognitive impairments induced by psychological stress in rats [J].Behav Brain Res,2009,202(1):71-76.

      [4] Avila I,Reilly MP,Sanabria F,et al.Modeling operant behavior in the Parkinsonian rat[J]. Behav Brain Res,2009,198(2):298-305.

      [5] Sanyal J,Bandyopalnyysk,Baneriee TK,et al.Plasma levels of lipid peroxides in patients with Parkinson, s disease [J].Eur Rev Med Pharmacol Sci,2009,13(2):129-132.

      [6]Sehriner SE,Abrahamyan A,Avanessian A,et a1.Decreased mitochondrial superoxide levels and enhanced protection in against paraquat in Drosophila melanogaster supplemented with Rhodiola roseal[J].Free Radic Res,2009,43(9):836-843.

      [7] 中華醫(yī)學(xué)會(huì)神經(jīng)病學(xué)分會(huì)運(yùn)動(dòng)障礙及帕金森病學(xué)組.帕金森病的診斷[J].中華神經(jīng)科雜志,2006,39(6):169-171.

      [8] Hoehn MM,Yahr MD. Parkinsonism:onset,progression,and mortality[J]. Neurology, 1967, 17:427-442.

      [9] Fahn S,Elton RL.Members of the URDPS Development committee:Unified Parkinson, s disease rating scale [C].In:Fahn S,Marsden CD,Calne DB,Goldstein M,editors.Recentdevelopment in Parkinson, s disease.2 nd ed,F(xiàn)lorham Park,NJ:MacMillan Healthcare Information,1987:153-164.

      [10]金萍.紅景天的研究現(xiàn)狀[J].光明中醫(yī),2011,26(7):1508-1511.

      [11] Wiegant FA,Surinova S,Ytsma E,et al.Plant adaptogens increase lifespan and stress resistance in C.elegans [J].Biogerontology,2009,10(1):27-42.

      [12] Panossian A,Wagner H.Stimulating effect of adaptogens:an overview with parricular reference to their efficaly following single dose administration [J]. Phy tother Res,2005,19(10):819-838.

      [13] Cai L,Wang H,Li Q, et al.Salidroside inhibits H2O2-induced apoptosis in PC12 cells by proventing cytochrome C release and inactivating of caspase cascade [J].Acta Biochim Biophys Sin(shang hai),2008,40(9):796-802.

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