Objective:Parkinson’s disease(PD)is the second largest neurodegenerative disease following Alzheimer’s disease(AD),which associated with aging.There are many similarities in pathology and pathogenesis,even in the TC...Objective:Parkinson’s disease(PD)is the second largest neurodegenerative disease following Alzheimer’s disease(AD),which associated with aging.There are many similarities in pathology and pathogenesis,even in the TCM theory understanding,so we can learn from each other in the process of drug discovery.The clinical results showed that Bushen-Yizhi formula(BSYZ)could effectively improve the neurological function score of senile dementia patients and had a better anti-dementia effect.Further pharmacological studies showed that BSYZ had neuroprotective effects,such as anti-inflammatory,anti-oxidation,anti-apoptosis and neurotrophic effects.In this study,the therapeutic effect of BSYZ on PD was evaluated in vivo and in vivo,and its molecular mechanism was discussed in order to expand the scope of application of BSYZ and to provide strategies for drug discovery of related neurodegenerative diseases.Methods:C57 BL/6 mice were injected intraperitoneally with MPTP to construct a PD mouse model.BSYZ(1.46,2.92,5.84 mg·kg-1)was administered for two weeks,and the positive control group was given a NSAID,piroxicam(12.5 mg·kg-1).After 1 week of pretreatment,MPTP was used to construct a PD mouse model.The mice were subjected to Rotation test on days 1,3 and 5,6th day.and the movement coordination and exercise ability of the drug on PD mice were observed on theThe number of TH-positive cells,Iba1 and CD68-labeled microglial cells in SNpc region were observed by immunofluorescence to observe the proliferation and activation of microglial cells and GFAP-labeled astrocytes.Western blotting was used to detect the nuclear transfer of NLRP3,Caspase-1,ASC,pro-IL-1β,IL-1βand NF-κB in the midbrain.Results:1.BSYZ could significantly improve the expression of MPTP model mice in the experiment of fatigue and Y-maze,increase the number of neurons in SNpc region and the positive expression of TH protein.2.BSYZ significantly inhibited the number of Iba1/CD68-positive microglial cells in MPTP-model mice and decreased the number of GFAP-positive astrocytes.3.BSYZ significantly inhibited the expression of NLRP3-associated protein in BV2 microglial cells induced by LPS+ATP and inhibited the nuclear transfer of NF-κB.Conclusion:BSYZ can effectively relieve the motor dysfunction of PD model mice,improve the damage of dopaminergic neurons,inhibit the proliferation and activation of microglial cells and astrocytes,and have good anti-MPTPinduced neuroinflammation and neuroinflammation mediated by nuclear transfer of NF-κB.The results show that BSYZ has a good prospect of anti-Parkinson’s disease and provides valuable drug discovery strategies for the related neurodegenerative diseases.展开更多
目的：观察补肾益智汤联合卡巴拉汀治疗阿尔兹海默症的临床效果及对血清缓激肽水平的影响。方法：选择医院收治的70例符合入组标准的阿尔兹海默症患者作为研究对象,按随机数字表分为研究组（35例）和对照组（35例）,对照组患者给予卡巴...目的：观察补肾益智汤联合卡巴拉汀治疗阿尔兹海默症的临床效果及对血清缓激肽水平的影响。方法：选择医院收治的70例符合入组标准的阿尔兹海默症患者作为研究对象,按随机数字表分为研究组（35例）和对照组（35例）,对照组患者给予卡巴拉汀治疗,研究组在对照组的基础上再口服补肾益智汤,4周为1个疗程,两组均治疗6个疗程,治疗前后进行中医症候积分、简易智能状态量表（mini-mantal state examination,MMSE）评分、修订韦氏记忆量表（WMS）、痴呆量表（Blessed-Roth）评分、阿尔兹海默症评定量表（ADAS-Cog）评分、日常生活能力量表（ADL）评分评判,取清晨空腹血,采用生物素双抗体夹心酶联免疫吸附法进行血清缓激肽（BK）检测,评价中医临床疗效,记录不良反应发生情况。结果：研究组治疗后记忆力减退、腰膝酸软、倦怠嗜卧、表情呆钝、善惊易恐、脑转耳鸣、面颊潮红等中医症候积分均较治疗前明显下降（P〈0.05）,而对照组仅记忆力减退明显改善（P〈0.05）。研究组和对照组治疗后MMSE、WMS明显升高（P〈0.05）,ADL、Blessed-Roth、ADAS-Cog明显降低（P〈0.05）,且研究组治疗后MMSE、WMS明显高于对照组（P〈0.05）,ADL、Blessed-Roth、ADAS-Cog明显低于对照组（P〈0.05）。研究组和对照组治疗后BK均明显降低（P〈0.05）,研究组治疗后BK明显低于对照组（P〈0.05）。研究组的中医临床疗效总有效率为82.86%,明显高于对照组62.86%,差异具有统计学意义（P〈0.05）。结论：阿尔兹海默症在卡巴拉汀治疗的基础上再加用补肾益智汤治疗的临床疗效明显,能有效改善患者认知功能、记忆功能、痴呆程度及日常生活能力,可能与其降低血清血清缓激肽水平有关。展开更多
目的探讨补肾益智方有效部位群对M146L细胞分泌的β淀粉样蛋白的影响,寻找潜在的具有抑制Aβ分泌的中药复方有效群。方法体外培养稳定转染人类阿尔茨海默病(AD)β淀粉样前体蛋白(beta-amyloid protein precursor,APP)基因及突变型早老素...目的探讨补肾益智方有效部位群对M146L细胞分泌的β淀粉样蛋白的影响,寻找潜在的具有抑制Aβ分泌的中药复方有效群。方法体外培养稳定转染人类阿尔茨海默病(AD)β淀粉样前体蛋白(beta-amyloid protein precursor,APP)基因及突变型早老素1(prsenilin-1,PS1)基因的中华仓鼠卵巢上皮细胞系(M146L),使之高效产生β淀粉样蛋白Aβ1-42,建立Aβ1-42过度表达的细胞模型。加入待筛选的补肾益智方有效提取部位群,用MTT法检测不同浓度的补肾益智方有效提取部位群(0,12.5,50μg/ml)对M146L细胞的毒性作用,应用Western blot免疫印迹方法分别检测突变型PS1M146L和野生型APP751双转染稳定表达CHO细胞系分泌的Aβ1-42的变化。结果不同浓度的补肾益智方有效部位群对M146L存活均无影响,不具有细胞毒作用。其中浓度为12.5μg/ml有效部位群F1和F2对M146L细胞分泌Aβ1-42有抑制作用。结论一定剂量的补肾益智方有效提取部位群对M146L细胞分泌的Aβ1-42有明显的抑制作用,其机制有待进一步研究。展开更多
文摘Objective:Parkinson’s disease(PD)is the second largest neurodegenerative disease following Alzheimer’s disease(AD),which associated with aging.There are many similarities in pathology and pathogenesis,even in the TCM theory understanding,so we can learn from each other in the process of drug discovery.The clinical results showed that Bushen-Yizhi formula(BSYZ)could effectively improve the neurological function score of senile dementia patients and had a better anti-dementia effect.Further pharmacological studies showed that BSYZ had neuroprotective effects,such as anti-inflammatory,anti-oxidation,anti-apoptosis and neurotrophic effects.In this study,the therapeutic effect of BSYZ on PD was evaluated in vivo and in vivo,and its molecular mechanism was discussed in order to expand the scope of application of BSYZ and to provide strategies for drug discovery of related neurodegenerative diseases.Methods:C57 BL/6 mice were injected intraperitoneally with MPTP to construct a PD mouse model.BSYZ(1.46,2.92,5.84 mg·kg-1)was administered for two weeks,and the positive control group was given a NSAID,piroxicam(12.5 mg·kg-1).After 1 week of pretreatment,MPTP was used to construct a PD mouse model.The mice were subjected to Rotation test on days 1,3 and 5,6th day.and the movement coordination and exercise ability of the drug on PD mice were observed on theThe number of TH-positive cells,Iba1 and CD68-labeled microglial cells in SNpc region were observed by immunofluorescence to observe the proliferation and activation of microglial cells and GFAP-labeled astrocytes.Western blotting was used to detect the nuclear transfer of NLRP3,Caspase-1,ASC,pro-IL-1β,IL-1βand NF-κB in the midbrain.Results:1.BSYZ could significantly improve the expression of MPTP model mice in the experiment of fatigue and Y-maze,increase the number of neurons in SNpc region and the positive expression of TH protein.2.BSYZ significantly inhibited the number of Iba1/CD68-positive microglial cells in MPTP-model mice and decreased the number of GFAP-positive astrocytes.3.BSYZ significantly inhibited the expression of NLRP3-associated protein in BV2 microglial cells induced by LPS+ATP and inhibited the nuclear transfer of NF-κB.Conclusion:BSYZ can effectively relieve the motor dysfunction of PD model mice,improve the damage of dopaminergic neurons,inhibit the proliferation and activation of microglial cells and astrocytes,and have good anti-MPTPinduced neuroinflammation and neuroinflammation mediated by nuclear transfer of NF-κB.The results show that BSYZ has a good prospect of anti-Parkinson’s disease and provides valuable drug discovery strategies for the related neurodegenerative diseases.
文摘目的：观察补肾益智汤联合卡巴拉汀治疗阿尔兹海默症的临床效果及对血清缓激肽水平的影响。方法：选择医院收治的70例符合入组标准的阿尔兹海默症患者作为研究对象,按随机数字表分为研究组（35例）和对照组（35例）,对照组患者给予卡巴拉汀治疗,研究组在对照组的基础上再口服补肾益智汤,4周为1个疗程,两组均治疗6个疗程,治疗前后进行中医症候积分、简易智能状态量表（mini-mantal state examination,MMSE）评分、修订韦氏记忆量表（WMS）、痴呆量表（Blessed-Roth）评分、阿尔兹海默症评定量表（ADAS-Cog）评分、日常生活能力量表（ADL）评分评判,取清晨空腹血,采用生物素双抗体夹心酶联免疫吸附法进行血清缓激肽（BK）检测,评价中医临床疗效,记录不良反应发生情况。结果：研究组治疗后记忆力减退、腰膝酸软、倦怠嗜卧、表情呆钝、善惊易恐、脑转耳鸣、面颊潮红等中医症候积分均较治疗前明显下降（P〈0.05）,而对照组仅记忆力减退明显改善（P〈0.05）。研究组和对照组治疗后MMSE、WMS明显升高（P〈0.05）,ADL、Blessed-Roth、ADAS-Cog明显降低（P〈0.05）,且研究组治疗后MMSE、WMS明显高于对照组（P〈0.05）,ADL、Blessed-Roth、ADAS-Cog明显低于对照组（P〈0.05）。研究组和对照组治疗后BK均明显降低（P〈0.05）,研究组治疗后BK明显低于对照组（P〈0.05）。研究组的中医临床疗效总有效率为82.86%,明显高于对照组62.86%,差异具有统计学意义（P〈0.05）。结论：阿尔兹海默症在卡巴拉汀治疗的基础上再加用补肾益智汤治疗的临床疗效明显,能有效改善患者认知功能、记忆功能、痴呆程度及日常生活能力,可能与其降低血清血清缓激肽水平有关。
文摘目的探讨补肾益智方有效部位群对M146L细胞分泌的β淀粉样蛋白的影响,寻找潜在的具有抑制Aβ分泌的中药复方有效群。方法体外培养稳定转染人类阿尔茨海默病(AD)β淀粉样前体蛋白(beta-amyloid protein precursor,APP)基因及突变型早老素1(prsenilin-1,PS1)基因的中华仓鼠卵巢上皮细胞系(M146L),使之高效产生β淀粉样蛋白Aβ1-42,建立Aβ1-42过度表达的细胞模型。加入待筛选的补肾益智方有效提取部位群,用MTT法检测不同浓度的补肾益智方有效提取部位群(0,12.5,50μg/ml)对M146L细胞的毒性作用,应用Western blot免疫印迹方法分别检测突变型PS1M146L和野生型APP751双转染稳定表达CHO细胞系分泌的Aβ1-42的变化。结果不同浓度的补肾益智方有效部位群对M146L存活均无影响,不具有细胞毒作用。其中浓度为12.5μg/ml有效部位群F1和F2对M146L细胞分泌Aβ1-42有抑制作用。结论一定剂量的补肾益智方有效提取部位群对M146L细胞分泌的Aβ1-42有明显的抑制作用,其机制有待进一步研究。
