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年龄相关性黄斑变性中医证型与多焦视网膜电图和血浆同型半胱氨酸及相关因素的关系研究
A Study on the Relation between TCM Syndrome Types in Age-related Macular Degeneration and Multifocal Electroretinogram, Plasma Homocysteine and Related Factors
【作者】 陈丽;
【导师】 曾庆华;
【作者基本信息】 成都中医药大学 , 中医眼科学, 2009, 博士
【摘要】 目的:通过检测年龄相关性黄斑变性(AMD)病人和正常人的多焦视网膜电图(mfERG)的一阶响应(FOK) P1、N1波的变化,分析mfERG FOK在AMD中医各证型中的诊断价值;研究血浆同型半胱氨酸(Hcy)及相关因素在AMD各中医证型中的变化及意义,观察Hcy是否为中国人群AMD发病的危险因素。对象与方法:①66例患者西医分为干性早期、湿性期,中医分为痰浊蕴结型、痰凝瘀滞型、肝肾亏虚型,采用RETI scan (Version 3.11)设备检测记录AMD患者和13例正常人mfERG FOK六个环、四个象限反应波波形。分析P1、N1波的反应密度及潜伏期在中医各证型中的变化特征。②采集51例AMD患者的血液样本,并以19例正常健康者作对照,酶联免疫法测定空腹血浆Hey水平,同时检测超氧化物歧化酶(SOD)、丙二醛(MDA)、血脂等生化指标水平。运用方差分析、多元回归分析、二元logistic回归分析等统计方法分析Hcy等指标与AMD中医证型的关系及相关因素对Hcy的影响,寻找AMD发病的危险因素。应用SPSS15.O软件进行统计学处理。结果:①mfERG的P1、N1波在痰浊蕴结型组与干性早期组的变化基本一致,在痰凝瘀滞型组、肝肾亏虚型组与湿性组变化相近。痰浊蕴结型组P1波1~3环、N1波1环反应密度下降(P<0.05),P1波1环,N1波2、3、5环潜伏期延迟(P<0.05),其余各环均未见差异(P>0.05);痰凝瘀滞型组P1波、N1波1~5环、肝肾亏虚型组P1波、N1波各环的反应密度均下降,但均以1~4环变化为主。四个象限的变化没有明显规律,从痰浊蕴结型→痰凝瘀滞型→肝肾亏虚型,P1、N1波平均反应密度逐渐下降,潜伏期逐渐延长,其中N1波潜伏期在各证型中均延长。②湿性对侧健眼组(湿对健组)1、2环处P1反应密度较对照组及干性对侧健眼组(干对健组)降低(P<0.05),各组在其余各环间比较无差异。③单眼湿性对侧干性眼组(湿对干组)与干性早期组比较P1、N1波在各环变化均无差异(P>0.05)。④Hcy水平在痰凝瘀滞型组、肝肾亏虚型组均高于对照组(P<0.05),三证型组间比较无差异(P>0.05)。⑤Hcy水平与SOD呈负相关。⑥SOD水平在痰凝瘀滞型组、肝肾亏虚型组均低于对照组及痰湿蕴结型组。MDA、TC、LDL-C水平在各证型组的均不同程度升高(P>O.05),TC水平在痰凝瘀滞型组、肝肾亏虚型组高于对照组(P<0.05);HDL-C水平组间比较无差异。结论:研究显示P1波1~3环、N1波1环反应密度,P1波1环、N1波2、3、5环潜伏期是痰浊蕴结型AMD眼视网膜功能变化的敏感指标;P1波1~4环、N1波1~3环反应密度更能反应痰凝瘀滞型AMD眼后极部视网膜的功能变化。P1、Nl波1~4环反应密度,P1波1~3环、N1波1、2、3、5、6环潜伏期的变化更能反应肝肾亏虚型AMD眼后极部视网膜的功能变化。单眼湿性AMD患者若对侧是健眼则可能发生AMD,若对侧为干性眼,则可能不会加重其干性眼的病情进展。高Hcy可能通过多种致病途径在痰凝瘀滞型与肝肾亏虚型AMD中发挥作用,但未发现是AMD发病的高风险因素;高TC、LDL-C可能是痰浊蕴结型AMD辨证和病程进展的微观指标;高TC、TG、LDL-C可能是痰凝瘀滞型、肝肾亏虚型AMD的生化物质基础;SOD水平减少、MDA生成增多可能为AMD发生发展的提供了病理基础。
【Abstract】 Purpose:To analyze the diagnostic value of different AMD TCM syndrome types with mfERG FOK by measuring P1, N1 wave for age-related macular degeneration(AMD) patients and the healthy. Also serum plasma homocysteine (Hcy), superoxide dismutase (SOD), malondialdehyde (MDA) and serum lipid levels were assayed to study the changes and significance with AMD TCM syndrome types. Then to determine if Hcy level is a risk factor in AMD among Chinese population.Objects and Methods:All 66 AMD patients were divided into early dry form and wet form in western medicine, and phlegm syndrome type, phlegm-blood stasis syndrome type and liver-kidney deficiency syndrome type in TCM. The patients and 13 healthy were measured with RETIscan (Version 3.11) by generating from 6 rings and 4 quadrants of mfERG FOK. Then all the data were analyzed in terms of response density and latency to correlate the variation characteristics among the different TCM syndrome types with response density and latency of P1, N1 waves. Only 51 AMD patients’blood samples were collected and 19 healthy samples. The fasting plasma homocysteine levels were measured by euzyme-linked immunosorbent assay. SOD, MDA, and blood fat concentration were also measured. And then correlated different AMD TCM syndrome types and all these indexes, and to find the influence on Hcy from the related factors and the independent factor of AMD. All the data were analyzed by ANOVA, multiple regression, Binary Logistic regression and so on.Results:①The magnitude of variations of FOK in phlegm syndrome group were consistent with dry AMD group basically, similar changes were also found between phlegm-blood stasis syndrome group as well as liver-kidney deficiency syndrome group and the wet AMD group. P1 wave in ring 1~3 and N1 wave in ring 1 of response densities decreased and P1 wave in ring 1, N1 wave in ring 2,3,5 of latencies delayed in phlegm group (P<0.05), response densities of P1 and Nl wave in ring 1-5 of phlegm-blood stasis syndrome group and any ring in liver-kidney deficiency syndrome group decreased, but mainly in ring 1-4. Response densities decreased and latencies delayed of PI, N1 waves increasingly from phlegm syndrome group to phlegm-blood stasis syndrome group to liver-kidney deficiency syndrome group, among which latency of N1 wave delayed in all syndrome groups.②The response densities in ring 1 of the asymptomatic fellow eyes of wet AMD group decreased compared with the control and asymptomatic fellow eyes of dry AMD groups(P<0.05). No differences were observed in other rings among the three groups.③No changes in the response densities and latencies were observed between one eye in dry form with contralateral wet AMD group and dry AMD group(P>0.05).④The Hcy levels in phlegm-blood stasis syndrome group and liver-kidney deficiency syndrome group were higher than those of the control(P<0.05), yet no differences were detected among three case groups(P>0.05).⑤My results demonstrated inverse correlation between Hcy and SOD level.⑥SOD levels in phlegm-blood stasis syndrome group and liver-kidney deficiency syndrome group were higher than controls and phlegm syndrome group(P<0.05), while TC level was higher than controls(P<0.05); MDA, TC and LDL-C levels all groups were elevated to different degrees(P<0.05). No difference of HDL-C level among four groups was found.Conclusions:Response density in ring 1-3 and latency in ring 1 of P1 wave, response density in ring 1 and latency in ring 2,3,5 of N1 wave of phlegm syndrome; response density in ring 1-4 of P1 wave and ring 1-3 of N1 wave of phlegm-blood stasis syndrome; response density in ring 1-4 of P1, N1 wave, latency in ring 1-3 of PI wave and ring 1,2,3,5,6 of N1 wave of liver-kiney deficiency syndrome among AMD eyes. It was also found that the asymptomatic fellow eyes of wet AMD are vulnerable to become dry AMD, while there is no advanced progression in eyes of dry form with contralateral wet AMD in this study. This research suggested that hyperhomocysteine may play roles in phlegm-blood stasis syndrome and liver-kidney deficiency syndrome AMD by various pathogenic mechanisms, but was not a risk factor of AMD in this survey. Increased TG and LDL-C levels may be microscopic indexes of syndrome differentiation and stage increasing in phlegm syndrome group. Increased TC, TG and LDL-C may be some of the useful markers of phlegm-blood stasis syndrome andliver-kidney deficiency syndrome. Increased SOD and decreased MDA may beregarded as pathological basis in AMD.
【Key words】 multifocal electroretinogram; age-related macular degeneration; TCM syndrome type; homocysteine;