肝豆汤加减治疗湿热内蕴型肝豆状核变性的临床疗效研究
|
摘要
目的了解肝豆汤加减治疗湿热内蕴型肝豆状核变性(Wilson病)的临床疗效,并探讨其作用机制。方法选取2016年1—8月在安徽中医药大学第一附属医院脑病中心住院治疗的湿热内蕴型Wilson病患者78例,采用随机数字表法分为对照组和观察组,各39例。两组患者入院后均以谷胱甘肽、二巯丙磺酸钠保肝驱铜为基础治疗,观察组在基础治疗的同时采用清热解毒、通腑利尿之中药肝豆汤加减治疗,两组患者均以4周为1个疗程。比较两组患者治疗前后的中医证候积分、血清同型半胱氨酸(Hcy)水平、血清肝纤维化标志物[透明质酸酶(HA)、Ⅳ型胶原(Ⅳ-C)、Ⅲ型前胶原(PCⅢ)、层粘连蛋白(LN)]水平及中医证候疗效。结果治疗前两组患者中医证候积分比较,差异无统计学意义(P>0.05);治疗后观察组患者中医证候积分低于对照组,差异有统计学意义(P<0.05)。两组患者中医证候疗效比较,差异无统计学意义(P>0.05)。治疗前两组患者血清Hcy水平比较,差异无统计学意义(P>0.05);治疗后观察组患者血清Hcy水平低于对照组,差异有统计学意义(P<0.05)。治疗前两组患者血清HA、Ⅳ-C、PCⅢ、LN水平比较,差异无统计学意义(P>0.05);治疗后观察组患者血清HA水平低于对照组,差异有统计学意义(P<0.05);但治疗后两组患者血清Ⅳ-C、PCⅢ、LN水平比较,差异无统计学意义(P>0.05)。结论在进行西医综合保肝驱铜治疗的同时,临床辨证使用肝豆汤加减治疗湿热内蕴型Wilson病可以改善患者的临床症状,调节血清肝纤维化标志物和Hcy水平,改善肝功能。其作用机制为通过通腑利尿法竞争性抑制铜离子在胃肠道的吸收,同时增加体内多余铜的排泄,从而减轻铜毒导致的脏器功能损伤。
Objective To investigate the therapeutic effect and mechanism of action of modified Gandou decoction in the treatment of Wilson's disease with endogenous damp-heat syndrome. Methods We enrolled 78 cases of Wilson' s disease with endogenous damp-heat syndrome who received inpatient treatment in Encephalopathy Treatment Center,the First Affiliated Hospital of Anhui University of Chinese Medicine from January to August 2016 and divided them into the observation group and the control group with 39 in each based on random number table. Both groups received glutathione( GSH) and sodium dimercaptosulphonate( DMPS) as the basic treatment for protecting liver function and decoppering. The observation group additionally received modified Gandou decoction for heat-clearing,detoxifying,clearing bowels and promoting diuresis. Four-week treatment was defined as one course of treatment. TCM syndrome scores,clinical effects, levels of serum homocysteine( Hcy),markers of liver fibrosis [hyaluronidase( HA),type Ⅳ collagen( Ⅳ-C),type Ⅲ procollagen( PC Ⅲ) and laminin( LN) ]and TCM syndrome treatment were measured and compared in both groups before and after treatment. Results The TCM syndrome scores did not differ significantly between the groups before treatment( P > 0. 05), but they decreased significantly in the observation group after treatment( P < 0. 05). TCM syndrome treatment in both groups were improved significantly,but showed no differences between the groups( P > 0. 05). The levels of Hcy were found to be similar in both groups before treatment( P > 0. 05); after treatment,they were decreased obviously in the observation group( P < 0. 05). The levels of HA,Ⅳ-C,PCⅢ and LN were similar in both groups before treatment( P > 0. 05); after treatment,the levels of HA decreased obviously in the observation group( P < 0. 05),but the levels of Ⅳ-C,PCⅢ and LN were still similar in both groups( P > 0. 05). Conclusion For patients with Wilson's disease with endogenous damp-heat syndrome,modified Gandou decoction based on syndrome differentiation combined with western drugs for protecting liver function and decoppering can improve the clinical symptoms,levels of markers of liver fibrosis and serum Hcy as well as the liver function. The mechanism is acted by decreasing gastrointestinal absorption of copper via clearing bowels and promoting diuresis and advancing the discharge of excess copper,so that the organ function damage caused by copper deposition is alleviated remarkably.
Objective To investigate the therapeutic effect and mechanism of action of modified Gandou decoction in the treatment of Wilson's disease with endogenous damp-heat syndrome. Methods We enrolled 78 cases of Wilson' s disease with endogenous damp-heat syndrome who received inpatient treatment in Encephalopathy Treatment Center,the First Affiliated Hospital of Anhui University of Chinese Medicine from January to August 2016 and divided them into the observation group and the control group with 39 in each based on random number table. Both groups received glutathione( GSH) and sodium dimercaptosulphonate( DMPS) as the basic treatment for protecting liver function and decoppering. The observation group additionally received modified Gandou decoction for heat-clearing,detoxifying,clearing bowels and promoting diuresis. Four-week treatment was defined as one course of treatment. TCM syndrome scores,clinical effects, levels of serum homocysteine( Hcy),markers of liver fibrosis [hyaluronidase( HA),type Ⅳ collagen( Ⅳ-C),type Ⅲ procollagen( PC Ⅲ) and laminin( LN) ]and TCM syndrome treatment were measured and compared in both groups before and after treatment. Results The TCM syndrome scores did not differ significantly between the groups before treatment( P > 0. 05), but they decreased significantly in the observation group after treatment( P < 0. 05). TCM syndrome treatment in both groups were improved significantly,but showed no differences between the groups( P > 0. 05). The levels of Hcy were found to be similar in both groups before treatment( P > 0. 05); after treatment,they were decreased obviously in the observation group( P < 0. 05). The levels of HA,Ⅳ-C,PCⅢ and LN were similar in both groups before treatment( P > 0. 05); after treatment,the levels of HA decreased obviously in the observation group( P < 0. 05),but the levels of Ⅳ-C,PCⅢ and LN were still similar in both groups( P > 0. 05). Conclusion For patients with Wilson's disease with endogenous damp-heat syndrome,modified Gandou decoction based on syndrome differentiation combined with western drugs for protecting liver function and decoppering can improve the clinical symptoms,levels of markers of liver fibrosis and serum Hcy as well as the liver function. The mechanism is acted by decreasing gastrointestinal absorption of copper via clearing bowels and promoting diuresis and advancing the discharge of excess copper,so that the organ function damage caused by copper deposition is alleviated remarkably.
引文
[1]LAI C H,TSENG H F.Population-based epidemiologic study of Wilson's disease in Taiwan[J].European Journal of Neurology the Official Journal of the European Federation of Neurological Societies,2010,17(6):830-833.DOI:10.1111/j.1468-1331.2009.02946.x.
[2]CHENG N,WANG K,HU W B,et al.Wilson disease in the south Chinese Han population[J].Canadian Journal of Neurological Sciences Le Journal Canadien Des Sciences Neurologiques,2014,41(3):363-367.DOI:org/10.1017/s0317167100017315.
[3]胡文彬,韩咏竹,薛本春,等.安徽省含山县肝豆状核变性的流病学研究[J].中华医学杂志,2011,91(13):894-897.DOI:10.3760/cma.j.issn.0376-2491.2011.13.008.HU W B,HAN Y Z,XUE B C,et al.Eepidemiological study of hepatolenticular degeneration at Hanshan County,Anhui Province[J].National Medical Journal of China,2011,91(13):894-897.DOI:10.3760/cma.j.issn.0376-2491.2011.13.008.
[4]COFFEY A J,DURKIE M,HAGUE S,et al.A genetic study of Wilson's disease in the United Kingdom[J].Brain A Journal of Neurology,2013,136(5):1476-1487.DOI:10.1093/brain/awt035.
[5]杨文明,韩辉,鲍远程,等.中医对肝豆状核变性病因病机及辨证论治的探索[J].北京中医药大学学报(中医临床版),2012,19(4):6-9.DOI:10.3969/j.issn.1672-2205.2012.04.002.YANG W M,HAN H,BAO Y C,et al.TCM etiology,pathogenesis and syndrome differentiation and treatment of epatolenticular degeneration[J].Journal of Beijing University of Traditional Chinese Medicine(Clinical Medicine),2012,19(4):6-9.DOI:10.3969/j.issn.1672-2205.2012.04.002.
[6]贾建平.神经病学[M].7版.北京:人民卫生出版社,2013:286-288.JIA J P.Neurology[M].7th ed.Beijing:People's Medical Publishing House(PMPH),2013:286-288.
[7]王翼洁,胡文彬,余小玲,等.肝豆状核变性患者血浆同型半胱氨酸与脂蛋白(a)、叶酸等的相关性研究[J].中华临床医师志,2014,8(20):6-10.DOI:10.3877/cma.j.issn.1674-0785.2014.20.002.WANG Y J,HU W B,YU X L,et al.Correlation between plasma homocysteine and lipoprotein(a),folate etc.in patients with hepatolenticular degeneration[J].Chinese Journal of Clinicians(Electronic Edition),2014,8(20):6-10.DOI:10.3877/cma.j.issn.1674-0785.2014.20.002.
[8]贾建平.神经病学[M].6版.北京:人民卫生出版社,2008.JIA J P.Neurology[M].6th ed.Beijing:People's Medical Publishing House(PMPH),2008.
[9]周仲英.中医内科学[M].6版.北京:中国中医药出版社,2002.ZHOU Z Y.Internal medicine of traditional Chinese medicine[M].6th ed.Beijing:China Press of Traditional Chinese Medicine,2002.
[10]杨文明,鲍远程,张波,等.肝豆状核变性诊疗方案[J].中医药临杂床杂志,2012,24(11):1130-1131.DOI:10.16448/j.cjtcm.2012.11.028.YANG W M,BAO Y C,ZHANG B,et al.Diagnosis and treatment of hepatolenticular degeneration[J].Clinical Journal of Traditional Chinese Medicine,2012,24(11):1130-1131.DOI:10.16448/j.cjtcm.2012.11.028.
[11]中华全国中医学会老年医学会.中医老年颤证诊断和疗效评定标准[J].北京中医学院学报,1992,34(4):39-41.Chinese Academy of Traditional Chinese Medicine,Geriatrics Society.Criteria for diagnosis and efficacy evaluation of senile fibrillation syndrome in traditional Chinese medicine[J].Journal of Beijing University of Traditional Chinese Medicine,1992,34(4):39-41.
[12]中华人民共和国原卫生部.中药新药临床研究指导原则[M].北京:中国中医药出版社,2002.Ministry of Health of the People's Republic of China.Guiding principles for clinical research of new drug of Chinese materia medica[M].Beijing:Chinese Medicine Press,2002.
[13]DALVI A,PADMANABAN M.Wilson's disease:etiology,diagnosis and treatment[J].Disease-a-month,2014,60(9):450-459.DOI:10.1016/j.disamonth.2014.07.002.
[14]杨文明,张春海,李瑞娟,等.毒邪在肝豆状核变性致病中的作用[J].中国实验方剂学杂志,2009,15(11):109-111.DOI:10.3969/j.issn.1005-9903.2009.11.037.YANG W M,ZHANG C H,LI R J,et al.Pathogenetic role of poison in Wilson's disease[J].Chinese Journal of Experimental Traditional Medical Formulae,2009,15(11):109-111.DOI:10.3969/j.issn.1005-9903.2009.11.037.
[15]韩辉,杨文明,张娟,等.肝豆状核变性的中医证候特征[J].中医药临床杂志,2014,26(1):16-19.DOI:10.16448/j.cjtcm.2014.01.008.HAN H,YANG W M,ZHANG J,et al.Characteristics of traditional Chinese medicine syndrome of hepatolenticular degeneration[J].Clinical Journal of Traditional Chinese Medicine,2014,26(1):16-19.DOI:10.16448/j.cjtcm.2014.01.008.
[16]杨文明,方芳,汪美霞,等.肝豆扶木汤治疗Wilson病肝纤维化的临床研究[J].中医药临床杂志,2014,26(11):1111-1113.DOI:10.16448/j.cjtcm.2014.11.010.YANG W M,FANG F,WANG M X,et al.Clinical study of liver decoction in the treatment of Wilson's disease with liver fibrosis[J].Clinical Journal of Traditional Chinese Medicine,2014,26(11):1111-1113.DOI:10.16448/j.cjtcm.2014.11.010.
[17]张卫东.大黄治疗重症肝炎机制浅析[J].中国民康医学,2008,20(4):293.DOI:10.3969/j.issn.1672-0369.2008.04.027.ZHANG W D.Analysis on the mechanism of severe hepatitis treated by rhubarb[J].Medical Journal of Chinese People's Health,2008,20(4):293.DOI:10.3969/j.issn.1672-0369.2008.04.027.
[18]黄古叶,龙富立,石清兰,等.大黄煎剂配合人工肝支持系统治疗重型肝炎临床研究[J].辽宁中医杂志,2008,35(10):1537-1538.DOI:10.3969/j.issn.1000-1719.2008.10.050.HANG G Y,LONG F L,SHI Q L,et al.Rhubarb decoction combined with artificial liver support system in severe hepatitis treatment:a clinical study[J].Liaoning Journal of Traditional Chinese Medicine,2008,35(10):1537-1538.DOI:10.3969/j.issn.1000-1719.2008.10.050.
[19]张晶晶,谈恒山.黄连素的临床应用研究进展[J].药学与临床研究,2015,23(3):287-290.DOI:10.13664/j.cnki.pcr.2015.03.022.ZHANG J J,TAN H S.Progress of berberine's clinical application[J].Pharmaceutical and Clinical Research,2015,23(3):287-290.DOI:10.13664/j.cnki.pcr.2015.03.022.
[20]郭少英,程发峰,钟相根,等.黄芩苷的体外抗氧化研究[J].时珍国医国药,2011,22(1):9-10.DOI:10.3969/j.issn.1008-0805.2011.01.004.GUO S Y,CHEN F F,ZHONG X G,et al.Antioxidative effects of baicalin in vitro[J].Lishizheng Medicine and Materia Medica Research,2011,22(1):9-10.DOI:10.3969/j.issn.1008-0805.2011.01.004.
[21]尹青,邓明明.穿心莲内酯抗炎作用机制研究进展[J].广东医学,2014,35(5):786-788.DOI:10.13820/j.cnki.gdyx.2014.05.061.YIN Q,DENG M M.Research progress of anti inflammatory mechanism of andrographolide[J].Guangdong Medical Journal,2014,35(5):786-788.DOI:10.13820/j.cnki.gdyx.2014.05.061.
[22]王志远,戴玲,张凯.半枝莲多糖的提取纯化及抗氧化活性研究[J].中国生化药物杂志,2008,29(2):96-99.WANG Z Y,DAI L,ZHANG K.Research on extraction techniques and antioxidant activity of polysaccharides from Scutellaria Barbata D.Don[J].Chinese Journal of Biochemical Pharmaceutics,2008,29(2):96-99.
[23]王国义.软肝散治疗肝炎肝纤维化78例[J].陕西中医,2011,32(5):523-524.DOI:10.3969/j.issn.1000-7369.2011.05.006.WANG G Y.Hepatic fibrosis treated by ruangan powder[J].Shaanxi Journal of Traditional Chinese Medicine,2011,32(5):523-524.DOI:10.3969/j.issn.1000-7369.2011.05.006.
[24]FAUX N G,ELLIS K A,PORTER L,et al.Homocysteine,vitamin B12,and folic acid levels in Alzheimer's disease,mild cognitive impairment,and healthy elderly:baseline characteristics in subjects of the Australian Imaging Biomarker Lifestyle study[J].Journal of Alzheimers Disease Jad,2011,27(4):909-922.DOI:10.3233/JAD-2011-110752.
[25]余小玲,胡文彬,吴君霞,等.肝豆状核变性与血浆同型半胱氨酸的相关性研究[J].安徽医学,2014,36(10):1347-1351.10.3969/j.issn.1000-0399.2014.010.005.YU X L,HU W B,WU J X,et al.Correlation study of hepatolenticular degeneration and plasma homocysteine[J].Anhui Medical Journal,2014,36(10):1347-1351.DOI:10.3969/j.issn.1000-0399.2014.010.005.
[2]CHENG N,WANG K,HU W B,et al.Wilson disease in the south Chinese Han population[J].Canadian Journal of Neurological Sciences Le Journal Canadien Des Sciences Neurologiques,2014,41(3):363-367.DOI:org/10.1017/s0317167100017315.
[3]胡文彬,韩咏竹,薛本春,等.安徽省含山县肝豆状核变性的流病学研究[J].中华医学杂志,2011,91(13):894-897.DOI:10.3760/cma.j.issn.0376-2491.2011.13.008.HU W B,HAN Y Z,XUE B C,et al.Eepidemiological study of hepatolenticular degeneration at Hanshan County,Anhui Province[J].National Medical Journal of China,2011,91(13):894-897.DOI:10.3760/cma.j.issn.0376-2491.2011.13.008.
[4]COFFEY A J,DURKIE M,HAGUE S,et al.A genetic study of Wilson's disease in the United Kingdom[J].Brain A Journal of Neurology,2013,136(5):1476-1487.DOI:10.1093/brain/awt035.
[5]杨文明,韩辉,鲍远程,等.中医对肝豆状核变性病因病机及辨证论治的探索[J].北京中医药大学学报(中医临床版),2012,19(4):6-9.DOI:10.3969/j.issn.1672-2205.2012.04.002.YANG W M,HAN H,BAO Y C,et al.TCM etiology,pathogenesis and syndrome differentiation and treatment of epatolenticular degeneration[J].Journal of Beijing University of Traditional Chinese Medicine(Clinical Medicine),2012,19(4):6-9.DOI:10.3969/j.issn.1672-2205.2012.04.002.
[6]贾建平.神经病学[M].7版.北京:人民卫生出版社,2013:286-288.JIA J P.Neurology[M].7th ed.Beijing:People's Medical Publishing House(PMPH),2013:286-288.
[7]王翼洁,胡文彬,余小玲,等.肝豆状核变性患者血浆同型半胱氨酸与脂蛋白(a)、叶酸等的相关性研究[J].中华临床医师志,2014,8(20):6-10.DOI:10.3877/cma.j.issn.1674-0785.2014.20.002.WANG Y J,HU W B,YU X L,et al.Correlation between plasma homocysteine and lipoprotein(a),folate etc.in patients with hepatolenticular degeneration[J].Chinese Journal of Clinicians(Electronic Edition),2014,8(20):6-10.DOI:10.3877/cma.j.issn.1674-0785.2014.20.002.
[8]贾建平.神经病学[M].6版.北京:人民卫生出版社,2008.JIA J P.Neurology[M].6th ed.Beijing:People's Medical Publishing House(PMPH),2008.
[9]周仲英.中医内科学[M].6版.北京:中国中医药出版社,2002.ZHOU Z Y.Internal medicine of traditional Chinese medicine[M].6th ed.Beijing:China Press of Traditional Chinese Medicine,2002.
[10]杨文明,鲍远程,张波,等.肝豆状核变性诊疗方案[J].中医药临杂床杂志,2012,24(11):1130-1131.DOI:10.16448/j.cjtcm.2012.11.028.YANG W M,BAO Y C,ZHANG B,et al.Diagnosis and treatment of hepatolenticular degeneration[J].Clinical Journal of Traditional Chinese Medicine,2012,24(11):1130-1131.DOI:10.16448/j.cjtcm.2012.11.028.
[11]中华全国中医学会老年医学会.中医老年颤证诊断和疗效评定标准[J].北京中医学院学报,1992,34(4):39-41.Chinese Academy of Traditional Chinese Medicine,Geriatrics Society.Criteria for diagnosis and efficacy evaluation of senile fibrillation syndrome in traditional Chinese medicine[J].Journal of Beijing University of Traditional Chinese Medicine,1992,34(4):39-41.
[12]中华人民共和国原卫生部.中药新药临床研究指导原则[M].北京:中国中医药出版社,2002.Ministry of Health of the People's Republic of China.Guiding principles for clinical research of new drug of Chinese materia medica[M].Beijing:Chinese Medicine Press,2002.
[13]DALVI A,PADMANABAN M.Wilson's disease:etiology,diagnosis and treatment[J].Disease-a-month,2014,60(9):450-459.DOI:10.1016/j.disamonth.2014.07.002.
[14]杨文明,张春海,李瑞娟,等.毒邪在肝豆状核变性致病中的作用[J].中国实验方剂学杂志,2009,15(11):109-111.DOI:10.3969/j.issn.1005-9903.2009.11.037.YANG W M,ZHANG C H,LI R J,et al.Pathogenetic role of poison in Wilson's disease[J].Chinese Journal of Experimental Traditional Medical Formulae,2009,15(11):109-111.DOI:10.3969/j.issn.1005-9903.2009.11.037.
[15]韩辉,杨文明,张娟,等.肝豆状核变性的中医证候特征[J].中医药临床杂志,2014,26(1):16-19.DOI:10.16448/j.cjtcm.2014.01.008.HAN H,YANG W M,ZHANG J,et al.Characteristics of traditional Chinese medicine syndrome of hepatolenticular degeneration[J].Clinical Journal of Traditional Chinese Medicine,2014,26(1):16-19.DOI:10.16448/j.cjtcm.2014.01.008.
[16]杨文明,方芳,汪美霞,等.肝豆扶木汤治疗Wilson病肝纤维化的临床研究[J].中医药临床杂志,2014,26(11):1111-1113.DOI:10.16448/j.cjtcm.2014.11.010.YANG W M,FANG F,WANG M X,et al.Clinical study of liver decoction in the treatment of Wilson's disease with liver fibrosis[J].Clinical Journal of Traditional Chinese Medicine,2014,26(11):1111-1113.DOI:10.16448/j.cjtcm.2014.11.010.
[17]张卫东.大黄治疗重症肝炎机制浅析[J].中国民康医学,2008,20(4):293.DOI:10.3969/j.issn.1672-0369.2008.04.027.ZHANG W D.Analysis on the mechanism of severe hepatitis treated by rhubarb[J].Medical Journal of Chinese People's Health,2008,20(4):293.DOI:10.3969/j.issn.1672-0369.2008.04.027.
[18]黄古叶,龙富立,石清兰,等.大黄煎剂配合人工肝支持系统治疗重型肝炎临床研究[J].辽宁中医杂志,2008,35(10):1537-1538.DOI:10.3969/j.issn.1000-1719.2008.10.050.HANG G Y,LONG F L,SHI Q L,et al.Rhubarb decoction combined with artificial liver support system in severe hepatitis treatment:a clinical study[J].Liaoning Journal of Traditional Chinese Medicine,2008,35(10):1537-1538.DOI:10.3969/j.issn.1000-1719.2008.10.050.
[19]张晶晶,谈恒山.黄连素的临床应用研究进展[J].药学与临床研究,2015,23(3):287-290.DOI:10.13664/j.cnki.pcr.2015.03.022.ZHANG J J,TAN H S.Progress of berberine's clinical application[J].Pharmaceutical and Clinical Research,2015,23(3):287-290.DOI:10.13664/j.cnki.pcr.2015.03.022.
[20]郭少英,程发峰,钟相根,等.黄芩苷的体外抗氧化研究[J].时珍国医国药,2011,22(1):9-10.DOI:10.3969/j.issn.1008-0805.2011.01.004.GUO S Y,CHEN F F,ZHONG X G,et al.Antioxidative effects of baicalin in vitro[J].Lishizheng Medicine and Materia Medica Research,2011,22(1):9-10.DOI:10.3969/j.issn.1008-0805.2011.01.004.
[21]尹青,邓明明.穿心莲内酯抗炎作用机制研究进展[J].广东医学,2014,35(5):786-788.DOI:10.13820/j.cnki.gdyx.2014.05.061.YIN Q,DENG M M.Research progress of anti inflammatory mechanism of andrographolide[J].Guangdong Medical Journal,2014,35(5):786-788.DOI:10.13820/j.cnki.gdyx.2014.05.061.
[22]王志远,戴玲,张凯.半枝莲多糖的提取纯化及抗氧化活性研究[J].中国生化药物杂志,2008,29(2):96-99.WANG Z Y,DAI L,ZHANG K.Research on extraction techniques and antioxidant activity of polysaccharides from Scutellaria Barbata D.Don[J].Chinese Journal of Biochemical Pharmaceutics,2008,29(2):96-99.
[23]王国义.软肝散治疗肝炎肝纤维化78例[J].陕西中医,2011,32(5):523-524.DOI:10.3969/j.issn.1000-7369.2011.05.006.WANG G Y.Hepatic fibrosis treated by ruangan powder[J].Shaanxi Journal of Traditional Chinese Medicine,2011,32(5):523-524.DOI:10.3969/j.issn.1000-7369.2011.05.006.
[24]FAUX N G,ELLIS K A,PORTER L,et al.Homocysteine,vitamin B12,and folic acid levels in Alzheimer's disease,mild cognitive impairment,and healthy elderly:baseline characteristics in subjects of the Australian Imaging Biomarker Lifestyle study[J].Journal of Alzheimers Disease Jad,2011,27(4):909-922.DOI:10.3233/JAD-2011-110752.
[25]余小玲,胡文彬,吴君霞,等.肝豆状核变性与血浆同型半胱氨酸的相关性研究[J].安徽医学,2014,36(10):1347-1351.10.3969/j.issn.1000-0399.2014.010.005.YU X L,HU W B,WU J X,et al.Correlation study of hepatolenticular degeneration and plasma homocysteine[J].Anhui Medical Journal,2014,36(10):1347-1351.DOI:10.3969/j.issn.1000-0399.2014.010.005.