拜颤停复方对帕金森病小鼠模型氧化应激反应的影响

目的:通过研究拜颤停复方(BCT)对1-甲基-4-苯基-1,2,3,6-四氢吡啶(MPTP)致小鼠帕金森病(PD)模型神经行为学、纹状体多巴胺(DA)含量、氧化应激反应的影响,探讨BCT对PD模型神经保护作用的可能作用机制。方法:雄性C57BL/6小鼠,MPTP-HC1(30 mg·kg-1·d-1,ip,0.9%生理盐水溶解)5 d,造成PD小鼠模型;设立正常组、模型组、多巴丝肼组(62.50 mg·kg-1·d-1)及BCT高、中、低剂量组(363.00,181.50,95.75 mg·kg-1·d-1),各给药组均用0.5%羧甲基纤维素钠(CMC-Na)溶解;BCT高、中、低剂量组ig给药治疗20 d后,进行爬杆实验和自主活动实验以观察小鼠行为学的变化;采用UPLC-MS-MS三重四级杆串联质谱技术检测小鼠纹状体多巴胺(DA)的含量;化学比色法检测小鼠黑质(SN)部位超氧化物歧化酶(SOD)、丙二醛(MDA)、谷胱甘肽过氧化物酶(GSH-Px)及单胺氧化酶B(MAO-B)。结果:与正常组比较,模型组小鼠爬杆时间显著延长(P0.05),自主活动次数显著减少(P0.05),纹状体DA含量、SOD及GSH-Px水平显著降低(P0.01),MDA及MAO-B水平显著升高(P0.01)。与模型组比较,经过BCT治疗,PD小鼠的神经行为学得到显著改善(P0.05),纹状体DA含量,SOD及GSH-Px水平显著升高(P0.01,P0.05),MDA及MAO-B水平显著降低(P0.01)。结论:BCT可以通过提高机体的抗氧化和清除自由基能力,明显改善PD小鼠的神经行为学变化及纹状体DA的含量,是其对PD模型神经保护作用的可能机制。     

补脑息风止痉汤对帕金森患者血清炎性因子的影响

目的:探究补脑息风止痉汤治疗帕金森对患者血清炎性因子的影响。方法:选取2017年3月至2018年4月四川省人民医院(东院)收治的帕金森患者69例,按照随机数字表法随机分为对照组(n=34)和观察组(n=35)。对照组给予左旋多巴治疗,观察组在对照组用药的基础上联合补脑息风止痉汤治疗,2组均连续治疗2个月。比较治疗前后2组UPDRS评分及中医症候积分;统计治疗后2组临床疗效;另检测并比较2组治疗前后认知功能及血清炎性因子变化。结果:与治疗前比较,治疗后2组UPDRS-Ⅰ、UPDRS-Ⅱ、UPDRS-Ⅲ、UPDRS-Ⅳ评分及观察组中医症候积分降低,且观察组低于对照组(P 0. 05);治疗后观察组临床总有效率高达88. 57%,较对照组的67. 65%显著升高(P 0. 05);与治疗前比较,治疗后2组MMSE、MoCA评分及观察组血清SOD水平升高,且观察组高于对照组(P 0. 05); 2组血清IL-6、IL-1β、MDA水平降低,且观察组低于对照组(P 0. 05)。结论:补脑息风止痉汤可显著改善帕金森患者临床症状,有效降低其血清炎性因子水平,并抑制氧化应激反应,提高患者认知功能,临床疗效显著优于常规西医治疗。     

黄芩苷对MPTP帕金森病小鼠的保护作用

目的观察黄芩苷对1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）帕金森病小鼠的保护作用。方法以10月龄（老龄）C5,BL小鼠腹腔注射MPTP（每天30mg／kg）3天制备小鼠帕金森病模型;黄芩苷组灌胃黄芩苷（每天100mg／kg,共15天）;用悬挂、游泳实验检测小鼠肢体运动功能;HPLC法测定小鼠脑纹状体多巴胺（DA）含量;分光光度法测定小鼠脑组织谷胱苷肽（GSH）、谷胱苷肽过氧化酶（GSH-Px）及丙二醛（MDA）的含量;小鼠脑冰冻切片,行酪氨酸羟化酶（TH）免疫组化染色,观察中脑黑质多巴胺能神经损伤情况。结果（1）模型组小鼠悬挂和游泳实验分值及脑纹状体DA含量均显著降低,黑质TH阳性细胞显著丢失,说明模型复制成功。（2）黄芩苷能够防止帕金森病小鼠黑质多巴胺能神经细胞丢失,防止模型小鼠纹状体DA含量的降低,并显著升高小鼠脑内GSH水平。但短时间给黄芩苷不能明显改善MPTP致帕金森病小鼠运动功能障碍。结论黄芩苷预防给药对MPTP致帕金森病小鼠有保护作用。     

The neuroprotective effect of modified Yeoldahanso-tang via autophagy enhancement in models of Parkinson's disease

Aim of study

Modified Yeoldahanso-tang (MYH) is a Korean herbal formula, containing 10 herbs: Pueraria lobata (Willd.) Ohwi, Angelica tenuissima Nakai, Scutellaria baicalensis Georgi, Platycodon grandiflorum (Jacq), Angelicae Dahurica, Cimicifuga heracleifolia Kom, Raphanus sativa L., Polygala tenuifolia (Willd.), Acorus gramineus Soland. and Dimocarpus longan Lour. The constitutive ratio of the ten herbs is at 6:4:2:1:2:2:2:4:6:6 in dry weight. MYH has been used to treat amnesia, hypochondria and dementia in Korea. In this study, we explored the possibility of using MYH in the prevention and treatment of Parkinson's disease (PD). Specifically, we made an effort to demonstrate the neuroprotective effects of MYH using experimental methods similar to those used in a recent study of PD.

Materials and methods

1-Methyl-4-phenylpyridinium (MPP+) (400 μM) was used to induce cytotoxicity in NGF (nerve growth factor)-differentiated PC12 cells. Cell viability was measured using a MTT assay. Induction of autophagy by MYH in NGF-differentiated PC12 cells was measured using an immunoblotting assay with LC3 and beclin 1 antibodies. The proteasomal inhibitor lactacystin (10 μM) was used to cause UPS dysfunction in NGF-differentiated PC12 cells. Clearance of aggregated proteins by MYH was measured using an immunoblotting assay with an ubiquitin antibody. 1-Methyl-4-phenyl-1,2,3,6-tetrahydrophenylpyridine (MPTP) (20 mg/kg, 4 times i.p.) caused substantia nigra injuries in C57BL/6 mice. Dopamine (DA) neurons were identified using a tyrosine hydroxylase-immunohistochemistry (TH-IHC) assay with a rabbit anti-TH antibody.

Results

Our findings indicate that MYH provides protection against MPP+-induced injury in NGF-differentiated PC12 cell. And MYH provides neuroprotection against lactacystin-induced NGF-differentiated PC12 cell death, which effect is partially mediated by autophagy enhancement through enhanced degradation of aggregated proteins. Additionally, in a C57BL/6 mice model with MPTP-induced substantia nigra injuries, MYH inhibits both the loss of TH-positive neurons in the substantia nigra pars compacta (SNpc) and the reduction of the optical density of TH-IR fibers in the striatum (ST).

Conclusions

All of our results indicate that MYH treatment has neuroprotective effects that are partially mediated by autophagy enhancement. MYH may be a promising herbal formula for the prevention and treatment of neurodegenerative diseases, especially PD.     

Supplementation with Herbal Extracts to Promote Behavioral and Neuroprotective Effects in Experimental Models of Parkinson's Disease: A Systematic Review

Parkinson's disease (PD) consists of a neurodegenerative pathology that has received a considerable amount of attention because of its clinical manifestations. The most common treatment consists of administering the drugs levodopa and biperiden, which reduce the effectiveness of the disease and the progress of its symptoms. However, phytotherapy treatment of PD has shown great potential in retarding the loss of dopaminergic neurons and minimizing the behavioral abnormalities. The aim of this study is to systematically review the use of supplemental herbal plants with cellular protective effect and behavioral activity in in vivo and in vitro experimental models. A total of 20 studies were summarized, where the effectiveness of herbal extracts and their isolated bioactive compounds was observed in animal models for PD. The main neurochemical mechanisms found in these studies are schematically represented. The herbal extracts and their biocompounds have antioxidant, anti‐apoptotic, and antiinflammatory properties, which contribute to avoiding neuronal loss. Reports show that besides acting on the biosynthesis of dopamine and its metabolites, these compounds prevent D2 receptors' hypersensitivity. It is suggested that further studies need be conducted to better understand the mechanisms of action of the bioactive compounds distributed in these plants. Copyright © 2017 John Wiley & Sons, Ltd.     

帕宁方对帕金森病大鼠行为及氧化应激反应的影响

目的:观察帕宁方对帕金森病(PD)大鼠行为和氧化应激反应的影响.方法:运用6-羟基多巴胺(6-OHDA)立体定向脑内注射复制PD大鼠模型.将PD模型大鼠随机分为模型组、阳性对照组(美多巴0.125 g·kg-1)与帕宁方高、中、低剂量组(按生药量计为84,42,21 g·kg-1),另设同期正常组、假手术组.观察各组治疗前后大鼠旋转圈数,测定大鼠中脑黑质纹状体活性氧(ROS)、丙二醛(MDA)、谷胱甘肽(GSH)含量,谷胱甘肽过氧化物酶(GSH-Px)、超氧化物歧化酶(SOD)的活性.结果:与模型组比较,帕宁方高、中、低剂量组大鼠旋转圈数为(237.26±19.23),(246.71±37.06),(278.81±20.09)圈,活性氧含量为( 231.02±10.11),( 235.87±12.76),(247.93±11.30) U·mg-1,MDA含量为(4.56±1.25),(4.70±1.17),(4.63±1.06) nmol·mg-1,均明显减少;GSH含量明显增多,为(6.20±0.81),(6.24±0.76),(6.18±0.90 )mg·g-1;GSH-Px活性为(2.68±0.27),(2.59±0.34),(2.31±0.22) nU·g-1,SOD活性为(188.40±5.86),( 170.87±9.80),(165.62±6.54)nU·mg-1,均明显增高,差异均有统计学意义(P＜0.05).结论:帕宁方能明显改善PD大鼠旋转行为,减轻其黑质纹状体氧化应激损伤.     

滋肾柔经汤改善帕金森病肝肾阴虚证的非运动症状

目的:探讨滋肾柔经汤改善帕金森病(PD)非运动症状肝肾阴虚证的临床疗效以及对血清脂联素(APN),尿酸(UA),肿瘤坏死因子-α(TNF-α)和白细胞介素-6(IL-6)水平的影响。方法:选择符合条件的108例患者,按随机数字表法分为对照组和治疗组,各54例;对照组给予美多巴片治疗,首次用量为1片/次,tid;治疗组在对照组用药基础上采取滋肾柔经汤治疗,qd,常规水煎2次,分早晚口服;两组患者疗程均12周。比较两组中医临床症状评分,非运动症状筛查问卷(NMSQuest)评分,帕金森病睡眠量表(PDSS)评分和汉密尔顿抑郁量表(HAMD)评分;分析两组疗后12周的疗效;检测两组血清APN,UA,TNF-α,IL-6水平。结果:治疗组治疗后中医症状评分均显著低于对照组(P0.01);治疗组的总有效率为87.04%,对照组为68.52%,治疗组明显高于对照组(P0.05);治疗组治疗后NMSQuest,HAMD评分显著低于对照组,PDSS评分显著高于对照组(P0.01);治疗后6,12周,治疗组患者血清APN和UA水平均高于同期对照组,而TNF-α,IL-6显著低于对照组(P0.01)。结论:在西药治疗基础上,滋肾柔经汤改善帕金森非运动症状肝肾阴虚证可显著改善中医症状和非运动症状,提高临床疗效,上调血清APN,UA水平,下调TNF-α,IL-6水平可能在其中发挥重要作用。     

针刺四关穴对帕金森病的疗效及相关机制研究

目的:探讨针刺四关穴对帕金森病(PD)临床疗效。方法:选取2017年12月至2019年1月宝安区中医院收治的PD患者60例进行回顾性分析,按照治疗方法不同分为对照组和观察组,每组30例。对照组予药物治疗联合脑深部电刺激治疗,观察组在对照组基础上加用针刺四关穴治疗,治疗8周。比较2组患者治疗前后氧化应激、帕金森综合量表评分(UPDRS评分)、生命质量测定简式量表(WHO-QOL-2)、肌电图震颤的差异及临床疗效。结果:1)治疗后2组患者精神、行为、情绪积分,日常活动积分、运动功能积分、运动并发症积分、UPDRS总评分、白细胞介素-1β(IL-1β)、白细胞介素-6(IL-6)、丙二醛(MDA)、固定姿势震颤的频率、强度和坐位静止震颤强度较治疗降低,生理、环境、独立性、社会关系、心理、WHO-QOL-2总评分、超氧化物歧化酶(SOD)、多巴胺(DA)较治疗前均升高(P<0.05),观察组优于对照组(P<0.05)。2)观察组显效率、总有效率为46.67%、86.67%,优于对照组的30%、73.33%,差异有统计学意义(P<0.05)。结论:针刺四关穴可改善PD病情,作用机制可能是抑制炎性反应和氧化应激反应有关。     

牵正散提取物对帕金森病模型小鼠震颤、运动障碍、黑质神经元超微结构的影响

目的:建立3种帕金森病小鼠模型,观察牵正散提取物对小鼠行为学影响,初步探讨其作用机制。方法:1昆明小鼠随机分组,设立模型组,牵正散低、高剂量组(1.7,5.0 g·kg-1),阳性药组(盐酸苯海索,3.35 mg·kg-1)。各治疗组小鼠连续ig给药4 d。末次给药后1 h,各组ip给予氢溴酸槟榔碱(25 mg·kg-1)或氧化震颤素(0.15 mg·kg-1)。记录各组小鼠震颤潜伏期和震颤持续时间。2C57BL/6小鼠随机分组,设立正常组,模型组,牵正散低、高剂量组剂量组(1.7,5.0 g·kg-1),阳性药组(美多芭,50 mg·kg-1)。除正常组,各组小鼠ip给予1-甲基-4-苯基-1,2,3,6-四氢吡啶(MPTP,30 mg·kg-1),连续5 d。第6天开始治疗组ig给予牵正散提取物和美多芭,连续7 d,末次给药后检测小鼠行为学变化,电镜观察黑质神经元结构变化。结果:1小鼠ip槟榔碱或氧化震颤素后出现明显震颤,与模型组比较,牵正散提取物高剂量组震颤潜伏期显著延长(P0.05),低、高剂量组震颤持续时间均显著缩短(P0.01)。2与模型组比较,小鼠ip MPTP后出现明显运动障碍,黑质神经元超微结构明显损伤,经牵正散提取物处理后,小鼠自主活动次数增加、转棒潜伏期延长、爬杆时间缩短(P0.05),黑质神经元线粒体等结构损伤程度减轻。结论:牵正散提取物显著抑制帕金森病模型小鼠震颤、改善运动障碍,其作用机制可能与减轻线粒体损伤、保护神经元有关。     

涤痰汤对帕金森病大鼠行为学和氧化应激反应的影响

目的观察涤痰汤对帕金森病（PD）大鼠行为学和氧化应激反应的影响。方法运用6-羟基多巴胺立体定向注射复制PD大鼠模型。将PD模型大鼠随机分为模型组与化痰组;另设正常组和假手术组,分别给予相应处理,共14d。观察各组治疗前后大鼠旋转圈数,测定大鼠中脑黑质纹状体活性氧、丙二醛、谷胱甘肽含量,谷胱甘肽过氧化物酶、超氧化物歧化酶的活性。结果与模型组比较,化痰组大鼠旋转圈数、活性氧及丙二醛含量明显减少,谷胱甘肽含量明显增多,谷胱甘肽过氧化物酶及超氧化物歧化酶活性明显增高,差异均有统计学意义（P〈0.05）;化痰组各氧化应激指标与正常组和假手术组之间的差异有统计学意义（P〈0.05）。结论涤痰汤能明显改善PD大鼠旋转行为,减轻其黑质纹状体氧化应激损伤。     

补肾化痰益智方联合丁苯酞对阿尔茨海默病患者氧化应激、血流变学及认知功能的影响

目的:探讨补肾化痰益智方联合丁苯酞对阿尔茨海默病(Alzheimer's disease,AD)患者氧化应激、血流变学及认知功能的影响。方法:2014年3月—2016年4月齐齐哈尔医学院附属第三医院共收治127例AD患者,以该批患者为研究对象,按随机数字表法分为治疗组(63例),对照组(64例)。两组患者同时给予丁苯酞软胶囊,在此基础上,治疗组加服补肾化痰益智方,连续治疗3个月后,对两组患者临床疗效,氧化应激、血液流变学与简易智力状态检查法(mini-mental state examination,MMSE)量表评分进行比较。结果:治疗组患者总有效率为93.65%,对照组为81.25%,治疗组高于对照组(P0.05);经治疗,两组AD患者全血高、低切黏度,红细胞聚集指数与红细胞压积均明显降低,且治疗组明显低于对照组(P0.05);与治疗前比较,治疗后,两组患者超氧化物歧化酶(super oxide dismutase,SOD),谷胱甘肽过氧化物酶(glutathione peroxidase,GPX-3)及过氧化氢酶(catalase,CAT)均明显提高,丙二醛(malonyldialdehyde,MDA)明显降低,且治疗组效果明显优于对照组(P0.05);与治疗前比较,治疗后两组MMSE评分及记忆力、注意力和计算力、定向力、语言能力、回忆能力均明显改善,且治疗组明显优于对照组(P0.05)。结论:补肾化痰益智方联合丁苯酞可以明显提高AD患者的认知功能,改善患者血液流变学,降低氧化刺激损伤,因此对AD具有积极的治疗效果。     

芍药甘草汤加减对MPTP诱导的帕金森病模型小鼠的影响

目的:研究芍药甘草汤加减对1-甲基-4-苯基-1,2,3,6-四氢吡啶(MPTP)诱导的帕金森病模型小鼠的作用。方法:将60只C57/BL6小鼠随机分为正常组,模型组,美多巴组(50 mg·kg~(-1))和芍药甘草汤加减低、中、高剂量组(1,2,4 g·kg~(-1))。将C57/BL6小鼠腹腔注射MPTP(40 mg·kg~(-1)),每天1次,连续7 d。除正常组和模型组每天灌胃生理盐水外,给药组每天灌胃1次相应的药物,灌药第3天后按上述方法造模(除正常组外),给药15 d后,检测各组小鼠的行为学(爬杆实验、游泳实验和悬尾实验)。采用酶联免疫吸附测定(ELISA)检测各组小鼠血清中胱抑素-C(Cys-C)和神经元特异烯醇化酶(NSE)的含量,采用分光光度法检测各组小鼠纹状体中超氧化物歧化酶(SOD),丙二醛(MDA)和谷胱甘肽过氧化物酶(GSH-PX)的水平,采用蛋白免疫印迹法(Western blot)检测各组小鼠纹状体中α-突触核蛋白(α-syn),酪氨酸羟化酶(TH),B淋巴细胞瘤-2基因(Bcl-2)和Bcl-2相关X蛋白(Bax)的表达。结果:与正常组比较,模型组小鼠的行为学实验中游泳实验得分和悬挂实验得分显著降低(P 0. 01),爬杆时间显著增加(P 0. 01),血清中Cys-C含量显著减少(P 0. 01),NSE含量明显增加(P 0. 05),纹状体中SOD水平和GSH-Px水平显著减少(P 0. 01),MDA水平明显增加(P 0. 05),TH表达和Bcl-2表达显著减少(P 0. 01),α-syn和Bax表达明显增加(P 0. 05);与模型组比较,芍药甘草汤加减各剂量组与美多巴组的行为学实验中游泳实验得分和悬挂实验得分均明显增加(P 0. 05),爬杆时间明显减少(P 0. 05),血清中Cys-C含量显著增加(P 0. 05),NSE含量显著减少(P 0. 05);纹状体中SOD水平和GSH-Px水平显著增加(P 0. 05),MDA水平明显减少(P 0. 05),纹状体中TH表达和Bcl-2表达明显增加(P 0. 05),α-syn和Bax表达明显减少(P 0. 05);与美多巴组比较,芍药甘草汤加减高剂量组的行为学实验中游泳实验得分和悬挂实验得分明显增加(P 0. 05),爬杆时间明显减少(P 0. 05),血清中Cys-C含量明显增加(P 0. 05),而NSE含量明显减少(P 0. 05);纹状体中SOD水平和GSH-Px水平明显增加(P 0. 05),MDA水平明显减少(P 0. 05),纹状体中TH和Bcl-2表达显著增加(P 0. 05),α-syn和Bax表达明显减少(P 0. 05)。结论:芍药甘草汤加减对MPTP诱导的帕金森病模型小鼠神经保护作用可能是通过抑制氧化损伤和细胞凋亡来实现的。     

帕金森病模型大鼠的氧化应激反应及绿茶多酚的干预作用

目的:探讨帕金森病大鼠氧化应激反应及绿茶多酚的干预作用。方法:采用6-羟基多巴胺(6-OHDA)偏侧损毁纹状体制备帕金森病大鼠模型,并随机分为模型组、绿茶多酚组,另取正常对照组、假手术组大鼠,每组10只。分别在6周后进行神经行为学检测后,取纹状体,应用比色法分别测定各组大鼠纹状体内超氧化物歧化酶(SOD)、丙二醛(MDA)、谷胱甘肽(GSH)、谷胱甘肽过氧化物酶(GSH-Px)的含量。结果:帕金森病模型组大鼠纹状体内SOD、GSH、GSH-Px的含量均明显减少,MDA含量呈增加趋势;而绿茶多酚组大鼠纹状体内SOD、GSH、GSH-Px的含量均呈现增加趋势,MDA含量呈减少趋势。结论:绿茶多酚能较好地改善帕金森病大鼠的氧化应激反应,可能通过清除自由基,减轻对细胞的损伤,从而缓解帕金森病的症状。     

大定风珠加减联合西药治疗伴发疼痛的帕金森患者疗效及作用机制

目的:探讨大定风珠加减联合西药治疗伴发疼痛的肝肾阴虚型帕金森(PD)患者的疗效及其作用机制。方法:选择伴发疼痛症状的肝肾阴虚型帕金森患者96例,随机分为对照组和观察组,各42例,均给予多巴丝肼片治疗,对照组给予复方海蛇胶囊治疗,观察组给予大定风珠加减治疗,连续治疗4周。比较2组患者的临床疗效、运动症状、生活质量、情感状态、精神状态及认知状况、腓总神经的传导速度(MCV),潜伏期(LP),波幅(Amp),血浆同型半胱氨酸(Hcy)及氧化应激相关指标及重组人帕金森病蛋白7(PARK7)和神经营养因子-3(NT-3)水平的变化。结果:观察组治疗总有效率明显高于对照组(P0.05)。治疗后,观察组患者运动症状明显优于本组治疗前及对照组(P0.05)。观察组的视觉模拟评分法(VAS),帕金森患者的生活质量问卷(PDQ-39)及帕金森氏病综合评分量表(UPDRS)评分均明显低于本组治疗前及对照组(P0.05)。观察组Hcy和氧化应激指标水平明显低于治疗前及对照组(P0.05)。观察组抗氧化指标水平,Amp及MCV水平明显高于本组治疗前及对照组(P0.05),而LP水平明显低于本组治疗前及对照组(P0.05)。治疗后,观察组血清PARK7明显低于治疗前及对照组,NT-3水平明显高于本组治疗前及对照组(P0.05)。结论:大定风珠加减联合西药治疗伴发疼痛的帕金森病患者可明显改善患者的疼痛症状,修复神经功能,提高生活质量,其机制可能与抑制患者过度的氧化应激状态有关。     

帕金森病的抗衰老辅助治疗机制研究

衰老是机体各种生化反应的综合表现,是体内外许多因素(环境污染、精神紧张、遗传等)共同作用的结果。人类社会逐步进入老龄化,老年人在社会中所占的比重越来越大,随着这一现象的发生,各种"老年病"发生的几率也越来越高。已有很多研究表明,抗衰老治疗对一些疾病的预防与辅助治疗具有价值,对帕金森病的治疗,已有临床及实验研究证明了抗衰老治疗的潜在价值,但对于帕金森病抗衰老治疗的作用机制至今没有明确的论述。为此,该文以具有临床报道的中医抗衰老方剂补阳还五汤为载体,探讨帕金森病的抗衰老治疗机制。研究结果发现,在抗衰老的几种机制中,线粒体损伤、细胞凋亡、自由基与氧化应激等机制有助于帕金森病的辅助治疗。该文以补阳还五汤为载体,但所发现的帕金森病的抗衰老辅助治疗机制不仅仅限于补阳还五汤,亦可通过其他抗衰老手段产生类似的结果。该文的贡献主要在于明确了帕金森病抗衰老治疗的机制,为帕金森病的辅助治疗与预防提供了新的策略。     

Neuroprotective Natural Products for the Treatment of Parkinson's Disease by Targeting the Autophagy–Lysosome Pathway: A Systematic Review

The autophagy–lysosome pathway (ALP) is a primary means by which damaged organelles and long‐lived proteins are removed from cells and their components recycled. Impairment of the ALP has been found to be linked to the pathogenesis of Parkinson's disease (PD), a chronic neurodegenerative disorder characterized by the accumulation of protein aggregates and loss of dopaminergic neurons in the midbrain. In recent years, some active compounds derived from plants have been found to regulate the ALP and to exert neuroprotective effects in experimental models of PD, raising the possibility that autophagy enhancement may be an effective therapeutic strategy in PD treatment. In this review, we summarize recent findings of natural products that enhance ALP and thereby protect against PD. Research articles were retrieved from PubMed using relevant keywords in combination. Papers related to the topic were identified, and then the reliability of the experiments was assessed in terms of methodology. The results suggest that targeting the ALP with natural products is a promising strategy for PD treatment. However, risk of bias exists in some studies due to the defective methodology. Rigorous experimental design following the guidelines of autophagy assays, molecular target identification and in vivo efficacy evaluation is critical for the development of ALP enhancers for PD treatment in future studies. Copyright © 2017 John Wiley & Sons, Ltd.     

重复经颅磁刺激改善帕金森患者认知对步态的影响

目的:探究重复经颅磁刺激对帕金森认知及步态影响性。方法:选取2014年1月至2018年1月解放军联勤保障部队第940医院安宁分院收治符合纳入条件帕金森患者82例作为研究对象,按照就诊顺序编号随机分为对照组和观察组,每组41例。对照组常规治疗,观察组加用重复经颅磁刺激治疗,均治疗4周。观察2组治疗前、完成治疗后脑内神经递质、炎性反应因子、步态、认知功能、帕金森统一评分量表(UPDRS)、计时运动、折返运动变化并比较;完成治疗后进行疗效比较。结果:1)完成治疗后2组C反应蛋白(CRP)、肿瘤坏死因子-α(TNF-α)较治疗前均显著下降(P 0. 05),完成治疗后观察组多巴胺(DA)、乙酰胆碱(Ach)、5-羟色胺(5-HT)较治疗前均显著升高(P 0. 05),对照组治疗前后差异无统计学意义(P 0. 05),完成治疗后观察组DA、Ach、5-HT较对照组显著升高,CRP、TNF-α显著下降(P 0. 05)。2)完成治疗后2组步长、步速、转身角速度、Berg评分较治疗前均显著升高(P 0. 05),完成治疗后观察组以上指标均显著高于对照组(P 0. 05)。3)完成治疗后2组重组人帕金森病蛋白7(PARK7)较治疗前均显著下降,蒙特利尔认知评估量表(MoCA)、简易精神状态量表(MMSE)较治疗前显著升高(P 0. 05),完成治疗后观察组MoCA、MMSE显著高于对照组,PARK7显著低于对照组(P 0. 05)。4)完成治疗后观察组精神行为情绪、日常生活活动、运动功能、折返运动、总分较治疗前均显著下降;计时运动较治疗前均显著升高(P 0. 05);对照组治疗前、完成治疗后比较,差异无统计学意义(P 0. 05);完成治疗后观察组计时运动显著高于对照组,余均显著低于对照组(P 0. 05)。5)完成治疗后观察组显效率、总有效率均显著高于对照组,比较差异有统计学意义(P 0. 05)。结论:重复经颅磁刺激能通过提高PD神经元递质,抑制炎性反应,从而改善认知功能和促进步态平衡。     

针灸治疗帕金森病自主神经功能障碍的临床研究进展

帕金森病（PD）是一种以静止性震颤、运动迟缓、肌张力增髙、姿势步态异常等症状,以及便秘、夜尿症等非运动症状为主要临床表现的神经系统变性疾病。近年来研究表明,针灸对于PD的非运动症状,尤其是PD自主神经功能障碍所造成的一系列症状如心血管系统功能障碍、泌尿系统功能障碍、胃肠道功能障碍等具有良好的调节作用,但尚无综述对此类研究加以整理。因此,现总结归纳PD自主神经功能障碍的病理特点、临床表现、发病机制及针灸治疗PD自主神经功能障碍的临床研究进展,分析针灸治疗PD自主神经功能障碍相关症状的优势,以期为进一步研究的开展提供参考资料。     

Effects of Five Ayurvedic Herbs on Locomotor Behaviour in a Drosophila melanogaster Parkinson's Disease Model

Current conventional treatments for Parkinson's disease (PD) are aimed at symptom management, as there is currently no known cure or treatment that can slow down its progression. Ayurveda, the ancient medical system of India, uses a combination of herbs to combat the disease. Herbs commonly used for this purpose are Zandopa (containing Mucuna pruriens), Withania somnifera, Centella asiatica, Sida cordifolia and Bacopa monnieri. In this study, these herbs were tested for their potential ability to improve climbing ability of a fruit fly (Drosophila melanogaster) PD model based on loss of function of phosphatase and tensin‐induced putative kinase 1 (PINK1). Fruit flies were cultured on food containing individual herbs or herbal formulations, a combination of all five herbs, levodopa (positive control) or no treatment (negative control). Tests were performed in both PINK1 mutant flies and healthy wild‐type (WT) flies. A significant improvement in climbing ability was observed in flies treated with B. monnieri compared with untreated PINK1 mutant flies. However, a significant decrease in climbing ability was observed in WT flies for the same herb. Centella asiatica also significantly decreased climbing ability in WT flies. No significant effects were observed with any of the other herbs in either PINK1 or WT flies compared with untreated flies. Copyright © 2014 John Wiley & Sons, Ltd.     

人参皂苷Re对帕金森病小鼠保护作用--人参皂甙Re抗黑质神经元凋亡的机制初探

目的 :研究人参皂苷Re对 1 甲基 4 苯基 1,2 ,3,6 四氢吡啶 ( 1 methy 4 phenyl 1,2 ,3,6 tetrahy dropyridine ,MPTP)诱致C5 7BL小鼠黑质神经元凋亡的保护作用及其可能机制。方法 :用MPTP皮下注射C5 7BL小鼠制备帕金森病 (Parkinson’sdisease ,PD)模型 ,灌胃给予人参皂苷Re预处理后 ,用TH组织化学染色 ,TUNEL染色观察黑质神经元的变化及凋亡情况 ;免疫组织化学检测Bcl 2 ,Bax蛋白表达。结果 :13mg·kg-1,2 6mg·kg-1人参皂苷Re预处理能使黑质致密带 (SNc)部位的TH染色阳性神经元增多 ,TUNEL染色阳性率降低 ,以及Bcl 2蛋白表达增加 ,Bax蛋白表达减少。结论 :人参皂苷Re对MPTP诱致小鼠黑质神经元凋亡有明显的保护作用 ;Bcl 2表达的升高和Bax表达的降低可能是人参皂苷Re抗凋亡的重要机制。