左旋多巴联合恩他卡朋治疗帕金森病疗效观察

祁  萌  夏  昱  刘永芳  李攀攀

郑州市第七人民医院神经内科，河南 郑州 450000

作者简介：祁萌，Email：463392363@qq.com

【摘要】  目的  研究左旋多巴联合恩他卡朋治疗帕金森病(PD)的疗效及对炎症因子、氧化应激指标水平的影响。方法  选取132例PD患者为研究对象，随机数字表法分成治疗组和对照组各66例。治疗组给予左旋多巴联合恩他卡朋治疗，对照组给予左旋多巴治疗。3个月后采用帕金森统一评分量表(UPDRS)比较2组临床疗效，记录其治疗前后血清炎症因子[白细胞介素-1β(IL-1β)、白细胞介素-6(IL-6)]、血浆氧化应激指标[超氧化物歧化酶(SOD)、谷胱甘肽(GSH)、丙二醛(MDA)水平变化情况。结果  2组治疗后UPDRS评分和IL-1β、IL-6、MDA水平均较治疗前显著降低(P＜0.05)，SOD、GSH水平则较治疗前显著升高(P＜0.05)，且治疗组变化幅度大于对照组(P＜0.05)；治疗组总有效率优于对照组(P＜0.05)。结论  左旋多巴联合恩他卡朋方案对PD患者体内炎症因子和氧化应激指标水平有一定调节作用，疗效确切，于病情转归有利。

【关键词】  左旋多巴；恩他卡朋；帕金森病；炎症因子；氧化应激

【中图分类号】  R742.5    【文献标识码】  A    【文章编号】  1673-5110(2018)20-2260-05  DOI：10.12083/SYSJ.2018.20.487

Department of Neurology，Seventh People's Hospital of Zhengzhou，Zhengzhou 450000，China

【Abstract】  Objective  To study the curative effect of levodopa combined with entacapone on Parkinson's disease (PD) and its influence on inflammatory factors and levels of oxidative stress indexes.Methods  132 patients with PD were randomly divided into treatment group and control group，with 66 cases in each group.The treatment group was treated with levodopa combined with entacapone，while the control group was treated with levodopa.The clinical effects in the two groups were compared 3 months after treatment by the Unified Parkinson's disease Rating scale (UPDRS)，the changes of serum inflammatory factors [interleukin-1β(IL-1β)，interleukin-6(IL-6)] and plasma oxidative stress indexes [superoxide dismutase (SOD)，glutathione (GSH)，malondialdehyde (MDA)] were collected and analyzed before and after treatment.Results  After treatment，the UPDRS scores and levels of IL-1β，IL-6 and MDA in the two groups were significantly decreased (P＜0.05)，the SOD and GSH levels in the two groups were significantly increased (P＜0.05)，and the decrease and increase in the treatment group were significantly higher than those in the control group (P＜0.05)；the total effective rate in the treatment group was higher than that in the control group (P＜0.05)．Conclusion  Levodopa combined with entacapone can promote the prognosis，regulate the levels of inflammatory factors and oxidative stress indexes in patients with PD，and its curative effect is definite.

【Key words】  Levodopa；Entacapone；Parkinson's disease；Inflammatory factor；Oxidative stress

        帕金森病(PD)是神经系统变性引起的静止性震颤等运动性障碍，常伴抑郁等非运动性障碍，严重影响老年人的身体健康和生活情况^[1-4]。该疾病进展缓慢，临床多采取药物治疗为主^[5-8]。本研究观察左旋多巴联合恩他卡朋对PD的疗效及对炎症因子、氧化应激指标水平的影响，以找寻相应有效方案。

1．1  一般资料  选取2017-08－2018-08于郑州市第七人民医院接受治疗的132例PD患者为研究对象，随机数字表法分成治疗组和对照组各66例。所有患者均符合PD临床诊断标准^[2]。排除合并自身免疫疾病者；严重心、肝、肺、肾疾病及恶性肿瘤者；左旋多巴或恩他卡朋用药禁忌者；长期服用其他抗炎药物者。132例患者随机分为治疗组与对照组，2组一般资料比较无显著差异(P＞0.05)，具有可比性。见表1。

1．2  治疗方法  对照组给予口服左旋多巴(生产企业：广东闰宝药业有限公司，规格：0.25 g，批准文号：国药准字H44023907)治疗，0.25 g/次，3次/d。治疗组在对照组的基础上另用恩他卡朋(生产企业：Novartis Europharm Ltd，规格：0.2 g，批准文号：H20140221)治疗，0.2 g/次，3次/d。2组均治疗3个月。

1．3  观察指标  治疗前及用药后3个月评估下列指标：(1)帕金森统一评分量表(UPDRS)^[9]评分：该量表涵盖四个部分，评分越高表示疾病越严重。(2)疗效评估^[10]：显效：UPDRS评分降幅＞50%；有效：UPDRS评分降幅20%～50%；无效：UPDRS评分降幅＜20%。总有效率＝(1－无效)/总例数×100%。(3)治疗前及治疗3个月后取患者清晨静脉血5 mL，离心分离血清、血浆，采用酶联免疫吸附法测定血清白细胞介素-1β(IL-1β)、白细胞介素-6(IL-6)水平、血浆超氧化物歧化酶(SOD)、谷胱甘肽GSH)、丙二醛(MDA)水平。

1．4  数据分析  所有数据采用 SPSS 19.0软件处理，计量资料以均数±标准差(x±s)表示，采用t检验，计数资料以百分率(%)表示，采用 χ² 检验，P＜0.05为差异有统计学意义。

2．1  2组UPDRS评分比较  治疗3个月后，2组UPDRS评分显著低于治疗前(P＜0.05)，且治疗组降幅大于对照组，差异有统计学意义(P＜0.05)。见表2。

2．2  2组疗效比较  治疗组总有效率显著高于对照组(P＜0.05)。见表3。

2．3  2组炎症因子水平比较  治疗3个月后，2组IL-1β、IL-6水平较治疗前显著降低(P＜0.05)，且治疗组降幅大于对照组(P＜0.05)。见表4。

2．4  2组氧化应激指标水平比较  治疗3个月后，2组MDA水平较治疗前显著降低(P＜0.05)，SOD、GSH水平较治疗前显著升高(P＜0.05)，且治疗组变化幅度大于对照组(P＜0.05)。见表5。

组别	n	性别(男/女)	年龄/岁	病程(a)	发病年龄/岁
治疗组	66	34/32	64.51±6.49	5.65±2.81	58.86±3.68
对照组	66	36/30	65.47±6.37	5.68±2.78	59.79±3.59
检验值		χ2＝0.122	t＝0.858	t＝0.062	t＝1.470
P值		0.727	0.393	0.951	0.144

表2  2组UPDRS评分比较  (x±s，分)

Table 2  Comparison of UPDRS scores between the two groups  (x±s，score)

组别	n	时间	UPDRSⅠ	UPDRSⅡ	UPDRSⅢ	UPDRSⅣ
治疗组	66	治疗前	4.58±3.19	20.54±6.56	27.07±9.48	2.54±1.45
		治疗后	2.08±1.73▲△	15.14±7.05▲△	19.42±9.47▲△	1.06±0.84▲△
对照组	66	治疗前	4.53±3.28	21.23±6.18	27.13±9.54	2.34±1.38
		治疗后	2.94±2.34▲	18.78±7.07▲	23.59±10.06▲	1.94±1.21▲

  注：与同组治疗前比较，^▲P＜0.05；与对照组治疗后比较，^△P＜0.05

表3  2组疗效比较  [n(%)]

Table 3  Comparison of efficacy between the two groups  [n(%)]

组别	n	显效	有效	无效	总有效
治疗组	66	23(34.85)	36(54.55)	7(10.61)	59(89.39) △
对照组	66	14(21.21)	34(51.52)	18(27.27)	48(72.73)

              注：与对照组比较，χ²＝5.971，^△P＝0.015

表4  2组炎症因子水平比较  (x±s)

Table 4  Comparison of levels of inflammatory cytokines between the two groups  (x±s)

组别	n	时间	IL-1β(ng/L)	IL-6(ng/L)
治疗组	66	治疗前	92.11±10.32	37.18±5.19
		治疗后	43.24±5.98▲△	18.54±3.56▲△
对照组	66	治疗前	92.89±10.28	37.17±4.98
		治疗后	52.62±6.64▲	25.45±4.42▲

              注：与同组治疗前比较，^▲P＜0.05；与对照组治疗后比较，^△P＜0.05

 表5  2组氧化应激指标水平比较  (x±s)

Table 5  Comparison of oxidative stress indexes between the two groups  (x±s)

组别	n	时间	MDA(μmol/mL)	SOD(U/mL)	GSH(μmol/mL)
治疗组	66	治疗前	9.18±1.73	69.23±10.28	18.12±2.14
		治疗后	5.14±0.65▲△	87.63±13.18▲△	52.58±6.37▲△
对照组	66	治疗前	9.22±2.07	69.31±10.24	18.09±2.21
		治疗后	7.76±1.04▲	78.54±11.08▲	36.74±3.81▲

              注：与同组治疗前比较，^▲P＜0.05；与对照组治疗后比较，^△P＜0.05

        多巴胺能神经元退行性病变所致多巴胺含量显著性减少是PD发病的主要病理过程^[11-14]。PD最主要的治疗手段是左旋多巴制剂和抗胆碱能药物为主的药物治疗^[15-20]。研究显示，左旋多巴联合恩他卡朋治疗PD获得显著疗效^[21-24]。

        已有文献表明，PD相关症状主要是由多巴胺减少所致的胆碱能神经细胞亢进功能缺乏抑制引起^[25-29]。左旋多巴为本身无药理活性的机体多巴胺合成前体物质，可通过血脑屏障进入中枢，与多巴脱羧酶作用生成多巴胺恢复多巴胺与乙酰胆碱平衡，达到抑制胆碱能神经细胞亢进的目的，改善PD症状^[30-32]。然而药物治疗过程中机体摄入的大部分左旋多巴未能进入中枢，而是在经外周血途中遭儿茶酚氧位甲基转移酶分解，到达药用部位的左旋多巴因余量过少难以发挥明显作用^[33-34]。恩他卡朋可抑制相关酶的活性避免左旋多巴分解，辅助左旋多巴入脑并充分发挥作用^[35]。本研究中，治疗前后UPDRS评分显示，左旋多巴联合恩他卡朋对PD患者症状改善有积极意义，且相对单纯左旋多巴治疗改善幅度更为显著。

        此外，有文献证实，PD发病与患者机体炎症反应和抗氧化功能缺陷联系紧密^[36-37]，导致PD患者产生多种运动与非运动功功能障碍的主要原因是其体内炎症因子水平过高和多巴胺神经元氧化与抗氧化功能失调^[38]。炎症因子可通过诱导多巴胺神经元细胞凋亡或阻碍神经元功能加剧PD，造成炎症反应与PD相互作用的恶性进展^[39-40]。多巴胺神经元抗氧化功能失调损害机体的自由基清除能力，引起氧化应激损伤损及多巴胺神经元细胞，造成功能障碍^[41-42]。MDA作为细胞膜脂质过氧化产物可通过间接反映细胞膜损伤程度体现机体抗氧化功能，SOD、GSH可通过抑制或清除氧自由基减轻氧化应激损伤发挥抗氧化作用。研究观察发现，PD患者经左旋多巴联合恩他卡朋治疗后血清炎症因子(IL-1β、IL-6)、血浆氧化应激指标(SOD、GSH、MDA)水平均趋于正常水平并改善明显，且改善效果优于单纯左旋多巴治疗。

        左旋多巴联合恩他卡朋治疗PD，可通过提供患者机体所缺多巴胺有效调节患者炎症因子及氧化应激指标水平、改善多巴胺神经元功能失调情况，对患者病情转归有利。

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(收稿2017-07-27  修回2018-10-09)

 本文责编：张喜民

本文引用信息：祁萌，夏昱，刘永芳，李攀攀．左旋多巴联合恩他卡朋治疗帕金森病疗效观察[J]．中国实用神经疾病杂志，2018，21(20)：2260-2264.DOI：10.12083/SYSJ.2018.20.487

Reference information：QI Meng，XIA Yu，LIU Yongfang，LI Panpan.Curative effect of levodopa combined with entacapone on Parkinson's disease[J]．Chinese Journal of Practical Nervous Diseases，2018，21(20)：2260-2264.DOI：10.12083/SYSJ.2018.20.487