智脑胶囊对实验性AD模型大鼠学习记忆及自由基代谢的影响1

目的 观察智脑胶囊对实验性AD模型大鼠学习记忆及自由基代谢的影响.方法采用β-淀粉样蛋白(β-AP)大鼠侧脑室注射,联用转移生长因子β1(TGF β1)脑内注射,制作实验性AD大鼠模型.在此基础上,应用避暗法和水迷路法测定AD模型大鼠学习记忆功能,并采用黄嘌呤氧化酶法、硫代巴比妥酸比色法分别测定实验性AD模型大鼠脑组织超氧化物歧化酶(SOD)活性和丙二醛(MDA)含量.结果经改进由β-AP联用TGF β1诱导的AD模型大鼠既表现有行为学改变(学习记忆障碍),又有典型的AD病理学特征(β-AP沉积斑),同时模型大鼠脑组织SOD活性明显下降,MDA含量显著增加.智脑胶囊能有效地改善实验性AD模型大鼠学习记忆功能,提高模型大鼠脑组织SOD活性,减少MDA含量.结论智脑胶囊能明显提高β-AP联用TGF β1诱导的实验性AD模型大鼠学习记忆能力,其机制与清除自由基密切相关.     

智脑胶囊对实验性AD模型大鼠学习记忆及自由基代谢的影响

目的 观察智脑胶囊对实验性AD模型大鼠学习记忆及自由基代谢的影响。方法 采用β－淀粉样蛋白（β－AP）大鼠侧脑室注射,联用转移生长因子β1（TGF β1）脑内注射,制作实验性AD大鼠模型。在此基础上,应用避暗法和水迷路法测定AD模型大鼠学习记忆功能,并采用黄嘌呤氧化酶法、硫代巴比妥酸比色法分别测定实验性AD模型大鼠脑组织超氧化物歧化酶（SOD）活性和丙二醛（MDA）含量。结果 经改进由β－AP联用TGF β1诱导的AD模型大鼠既表现有行为学改变（学习记忆障碍）,又有典型的AD病理学特征（β－AP沉积斑）,同时模型大鼠脑组织SOD活性明显下降,MDA含量显增加。智脑胶囊能有效地改善实验性AD模型大鼠学习记忆功能,提高模型大鼠脑组织SOD活性,减少MDA含量。结论 智脑胶囊能明显提高β－AP联用TGF β1诱导的实验性AD模型大鼠学习记忆能力,其机制与清除自由基密切相关。     

水飞蓟宾对D-半乳糖诱导衰老大鼠抑制糖氧化应激反应及改善学习记忆作用

目的:观察水飞蓟宾对D-半乳糖(D-gal)诱导衰老大鼠糖化氧化应激反应及学习记忆作用的影响。方法:采用D-gal诱导衰老大鼠模型;采用Morris水迷宫测定法检测大鼠学习记忆能力。实验结束后测定大鼠血浆糖化血红蛋白(HbA1c)、血浆非酶糖基化终产物(AGEs)和果糖胺(FRA)含量、红细胞醛糖还原酶(AR)活性及脑组织超氧化物歧化酶(SOD)活性和丙二醛(MDA)、AGEs含量。结果:水飞蓟宾150mg/kg和75mg/kg均能明显抑制D-gal诱导的AR活性增高(P<0.01),降低FRA、HbA1c和AGEs含量(P<0.01或P<0.05),能不同程度地降低大鼠脑组织AGEs和MDA含量,提高SOD活性(P<0.01)。结论:水飞蓟宾对D-半乳糖所致衰老大鼠学习记忆障碍具有保护作用,能增强学习记忆能力,其机制可能与抑制糖氧化应激反应有关。     

淫羊藿苷对淀粉样β蛋白片段25-35所致大鼠学习记忆障碍的改善作用

目的观察淫羊藿苷对淀粉样β蛋白片段25-35(Aβ25-35)所致阿尔茨海默病(AD)模型大鼠学习记忆能力的保护作用,并探讨其可能的作用机制。方法Wistar雄性大鼠,右侧海马内注射Aβ25-3510μg制备AD模型,次日起淫羊藿苷30,60和120mg.kg-1灌胃给药,连续14d,d15～19Morris水迷宫检测大鼠空间辨别学习记忆能力;d20检测海马组织中谷胱甘肽过氧化物酶(GSH-PX)、超氧化物歧化酶(SOD)及一氧化氮合酶(NOS)的活性,免疫组化法检测海马内乙酰胆碱酯酶(AChE)和胆碱乙酰转移酶(ChAT)的表达。结果与模型对照组比较,淫羊藿苷给药14d明显改善大鼠学习记忆能力;海马组织中SOD和GSH-PX活性升高,NOS活性降低;海马内AChE及ChAT的表达增加。结论淫羊藿苷可以改善Aβ25-35海马内注射所致AD模型大鼠的学习记忆能力,其作用可能与其增加AChE和ChAT表达,增强SOD和GSH-PX等自由基清除酶活性,降低NOS活性,减少NO释放等多种机制,促进胆碱能递质系统功能的恢复有关。     

华中五味子酮对阿尔茨海默病模型大鼠学习记忆的影响及其机制的研究

目的观察华中五味子酮(schisandrone)对阿尔茨海默病(AD)模型大鼠学习记忆及大脑内过氧化氢酶(CAT)、谷胱苷肽过氧化物酶(GSH-Px)、超氧化物歧化酶(SOD)活性的影响,探讨华中五味子酮对AD可能的防治作用。方法30只雄性SD大鼠,周龄8~12周,体质量250~300 g,随机分为3组:空白对照组、AD模型组和华中五味子酮干预组(每组10只)。采用侧脑室立体定向注射Aβ25-35(溶于无菌生理盐水,浓度10 mmol/L)的方法,建立AD的动物模型,并用华中五味子酮(溶于玉米油,浓度2 mmol/L)灌胃进行药物干预,测定各组Morris水迷宫逃避潜伏期,通过化学比色法观察各组大鼠脑组织CAT、GSH-Px、SOD的活性。结果与对照组比较,AD模型组大鼠的逃避潜伏期较长,而且其脑组织内CAT、SOD及GSH-Px活性较低,而用华中五味子酮干预的AD样大鼠的逃避潜伏期较AD模型组缩短(P<0.05),而且其大脑内CAT、SOD及GSH-Px活性较AD样大鼠显著增高(P<0.05或P<0.01)。结论五味子酮能够显著提高Aβ25-35介导的AD模型大鼠的学习记忆能力,可能与其提高大脑内抗氧化酶系统(CAT、SOD、GSH-Px)活性,促进氧自由基的清除有关。     

神经干细胞对AD大鼠行为及突触素Ⅰ表达的影响

目的:探究神经干细胞(NSCs)移植对β-淀粉样蛋白(Aβ1-42)诱导的阿尔茨海默病(AD)大鼠学习记忆能力及海马组织内突触素I表达的影响。方法:采用β-淀粉样蛋白(Aβ1-42)注射到大鼠海马组织内建立阿尔茨海默病(AD)大鼠动物模型,通过Y迷宫测试大鼠学习记忆能力和Western blot技术检测大鼠海马组织内Synapsin I表达。结果:与对照组比较,AD模型组、细胞移植组大鼠学习记忆和大鼠海马组织内Synapsin I蛋白表达量均低(P<0.05),与AD模型组比较,细胞移植组大鼠学习记忆能力和大鼠海马组织内Synapsin I蛋白表达量均较高(P<0.05)。结论:NSCs能显著改善AD大鼠的学习记忆能力,可能与上调突触素Ⅰ的表达有关。     

脑康泰胶囊对阿尔茨海默氏病大鼠学习记忆作用的影响

目的：观察脑康泰胶囊对阿尔茨海默氏病模型大鼠学习记忆作用的影响。方法：采用脑立体定向颅内注射啉酸所致阿尔第默氏病（Alzheimers disease.AD)大鼠模型的方法。结果：脑康泰胶囊可显著增加强AD大鼠被动学习和主动学习的能力。调节脑组织中单胺类递质含量及血清中相关激素水平,并显著改善AD模型大鼠的脑电图。结论：脑康泰胶囊显著改善AD大鼠学习记忆能力的作用,其机制与其调节中枢递质及激素水平等相关。     

水飞蓟宾对锰致神经毒性的干预研究

目的研究不同剂量的水飞蓟宾(silibinin)对锰致人神经母细胞瘤SH-SY5Y细胞毒性的对抗作用及可能机制。方法体外培养SH-SY5Y细胞,加入不同浓度的水飞蓟宾(5~20μmol/L),继续培养24 h,吸出后加入MnCl2(终浓度为0.6 mmol/L),MTT法检测细胞活力,Western blot检测自噬标志蛋白LC3和Beclin-1的表达和活化情况,DCFH-DA染色检测活性氧(ROS)含量,同时检测水飞蓟宾的体内外抗氧化活性。结果 MTT结果显示(5~20μmol/L)的水飞蓟宾对MnCl2诱导的细胞损伤有显著的拮抗作用。Western blot结果显示水飞蓟宾能剂量依赖性地抑制MnCl2处理诱导的自噬性损伤的发生。与对照组相比,0.6 mmol/L的MnCl2处理组ROS含量明显升高,而水飞蓟宾给药则能显著抑制ROS的产生,同时体内外的抗氧化能力检测显示水飞蓟宾抗具有较强的总抗氧化能力和抗超氧阴离子自由基活力,能显著恢复细胞内GSH和SOD的活力。结论水飞蓟宾能剂量依赖性地对抗MnCl2诱导的SH-SY5Y细胞损伤,这一作用可能是通过清除细胞内ROS继而抑制自噬性死亡的发生来实现的。     

二十二碳六烯酸-磷脂对AD大鼠学习记忆的影响

目的 研究二十二碳六烯酸-磷脂(docosahexaenoic acid-phosphatidylcholine, DHA-PC)对海马CA1区注射Aβ25-35所致的阿尔茨海默病（Alzheimer’s disease,AD）大鼠模型学习记忆能力改善作用,为DHA-PC的药用开发奠定理论基础。方法 SPF级雄性Wistar大鼠40只,250~300 g,随机分为正常对照组、AD组、多奈哌齐组、DHA-PC组。大鼠双侧海马CA1区注射Aβ25-35制作AD大鼠模型,水迷宫检测学习记忆能力改变,检测Tau(Ser 396)蛋白的含量,检测超氧化物歧化酶活性。结果 水迷宫结果显示：与AD组相比,定向航行实验DHA-PC组大鼠的潜伏期明显降低（P<0.05）;空间探索实验DHA-PC组大鼠在安全平台所在象限的活动时间明显增加（P<0.05）。与AD组相比,DHA-PC组和DHCI组大鼠皮层和海马的Tau（Ser396）蛋白含量明显降低（P<0.05,P<0.01）,DHA-PC组和DHCI组皮层SOD活性增强（P<0.01）。结论 DHA-PC可通过降低皮层和海马396位点磷酸化Tau蛋白的表达和增强SOD活性,改善AD大鼠学习记忆能力,具有较好的药用开发前景。     

松果菊苷对阿尔采末病模型大鼠学习、记忆功能及氧自由基水平的影响

目的研究松果菊苷(ECH)对Aβ25-35引起的阿尔采末病(AD)大鼠的学习与记忆能力的改善和氧自由基水平的影响。方法 60只SD大鼠,体质量(300±10)g,随机分为假手术组、模型组、ECH高、中、低剂量组(40、20、10 mg·kg-1·d-1)、阳性药石杉碱甲组(Hup-A,0.02 mg·kg-1·d-1)。水迷宫实验评价其学习记忆能力的改变。检测大脑皮质和海马中丙二醛(MDA)、一氧化碳(NO)的含量和超氧化物歧化酶(SOD)、一氧化氮合酶(NOS)的活性。结果 Aβ25-35能够严重损害大鼠学习记忆能力;与模型组大鼠相比,ECH不同剂量治疗组均能够减少其对学习记忆能力的损害(P<0.01,P<0.05)。ECH治疗组大鼠大脑皮质和海马组织中的MDA含量明显下降,SOD的活性明显升高,明显减少NO、NOS的释放(P<0.01,P<0.05)。结论 ECH可以改善AD大鼠学习记忆力,其作用机制可能与加快氧自由基的清除能力和降低大鼠脑内氧化应激水平有关。     

荔枝核皂苷对老年痴呆大鼠的干预作用研究

目的:建立老年痴呆(Alzheimer’s disease,AD)大鼠模型,探讨荔枝核皂苷对AD大鼠的治疗作用及其机制。方法:50只SD大鼠分为:对照组、模型对照组和低、中、高剂量荔枝核皂苷治疗组,共5组,每组10只;Morris水迷宫实验检测各组大鼠的逃避潜伏时间和平台跨越次数;Western blot实验检测各组脑组织β淀粉样蛋白(β-amyloid protein,Aβ)的表达变化;流式细胞仪检测各组脑组织活性氧(ROS)表达的改变。结果:AD大鼠模型组与对照组比较,逃避潜伏时间出现显著性地延长(P<0.01),平台跨越次数显著性地减少(P<0.01)。荔枝核皂苷治疗后AD大鼠的逃避潜伏时间和平台跨越次数得到显著性地改善(P<0.05)。AD大鼠脑组织Aβ的表达水平显著高于正常对照组,高、中、低剂量荔枝核皂苷治疗组可以剂量依赖性地降低模型鼠脑组织中Aβ的表达水平。对照组、模型对照组、低剂量荔枝核皂苷治疗组、中剂量荔枝核皂苷治疗组、高剂量荔枝核皂苷治疗组ROS表达水平的相对值分别为6.12±0.61、9.54±1.42、8.33±1.26、7.68±1.14、7.23±0.73,模型组显著高于对照组(P<0.01),荔枝核皂苷治疗可以显著降低模型组脑组织中ROS的表达水平(P<0.05)。结论:荔枝核皂苷具有抗AD大鼠痴呆的活性,减少AD大鼠脑组织Aβ和ROS的生成是其主要的作用机制。     

人参皂苷Rg1脂质体对东莨菪碱诱导大鼠学习记忆障碍的改善及其作用机制

目的：观察人参皂苷Rg1脂质体（Rg1-L）对东莨菪碱诱导大鼠学习记忆障碍的改善，并探讨其相关机制，方法：制备东莨菪碱诱导大鼠学习记忆障碍模型。采用Y型迷宫评价Rg1-L对模型大鼠学习记忆的影响，并测定大鼠大脑皮质中乙酰胆碱酯酶活性。结果：Rg1-L可以显著改善模型大鼠学习记忆功能。同时抑制大脑皮质中乙酰胆碱酯酶活性。结论：Rg1-L对东莨菪碱诱导大鼠学习记忆障碍模型大鼠的学习记忆功能有显著的改善作用，其机制可能与抑制大脑皮质中乙酰胆碱酯酶活性、提高人参皂苷Rg1生物利用度有关。     

红景天水提物和辅酶Q_(10)合用对小鼠学习记忆的协同促进作用

目的研究红景天水提物和辅酶Q10对Alzheimer病模型的协同保护作用。方法通过乙酰胆碱酯酶体外试验、NaCN及缺糖引起的PC12神经细胞损伤模型、东莨菪碱所致记忆障碍模型小鼠试验,并采用水迷宫评价促智作用,以小鼠皮层内乙酰胆碱酯酶活性,血清中单胺氧化酶、超氧化物歧化酶及丙二醛的活性水平为指标,检测红景天水提物和辅酶Q10的促智作用。结果红景天水提物和辅酶Q10对乙酰胆碱酯酶具有协同抑制作用,对神经细胞损伤具有协同保护作用,对东莨菪碱所致小鼠的空间辨别学习记忆障碍具有明显协同改善作用。结论红景天水提物和辅酶Q10对动物学习记忆有明显协同促进作用,其作用机制可能与红景天水提物能抑制胆碱酯酶活性而辅酶Q10有抗氧化作用有关。     

DHA型磷脂酰丝氨酸对东莨菪碱痴呆模型小鼠学习记忆力的影响

目的 研究富含DHA的磷脂酰丝氨酸（DHA-PS）对老年痴呆小鼠学习记忆的影响。方法 通过对小鼠腹腔注射东莨菪碱建模,并进行行为学测试和测定小鼠海马组织中的乙酰胆碱（Ach）、乙酰胆碱酯酶（AchE）和超氧化物歧化酶（SOD）的活力。实验分组为：正常对照组（N）、模型组（AD）、多奈哌齐阳性对照组（P）、DHA-PS组和DHA与磷脂酰丝氨酸（PS）的混合物组（DHA+PS）。 结果 富含DHA的磷脂酰丝氨酸（DHA-PS）能降低水迷宫潜伏期,提高穿越平台次数和目标象限停留时间,能明显抑制AchE的活力和提高SOD的活力,而DHA+PS组效果比较差。结论 富含DHA的磷脂酰丝氨酸（DHA-PS）通过影响中枢胆碱能神经系统和脑内抗氧化系统,改善了东莨菪碱所致痴呆小鼠学习记忆能力且与其分子形式有关。     

Effects of GBEE on memory impairment induced by scopolamine in mice and activity of AChE in cerebral cortex

OBJECTIVE The fruit of Ginkgo biloba L.is also known as Ginkgo nuts. Ginkgo has the effect of warming the lung, boosting qi, downbear phlegm, dispersing toxin, kil ing worms and etc, which also recorded in ancient books on tumor treatment. The scientific name of succulent skin is exocarp in Gingko nuts. Research shows that GBEE(Ginkgo biloba exocarp extracts) has anti-tumor,anti-aging and immune promoting activity. As an M receptor blocker, scopolamine can block the excitatory effect of acetylcholine on M receptors, causing learning and memory dysfunction. It can partially simulate some features of the cholinergic system of Alzheimer disease(AD). The learning and memory impairment model of scopolamine is the classic screening model for AD drug research. In this paper, the effects of GBEE on scopolamine induced learning and memory impairment in mice and its mechanism were preliminarily studied. METHODS GBEE was prepared by the patented method(patent: ZL201610916394.4). Infrared Spectroscopy(IR) analysis shows that the proteoglycan in GBEE is ester linkage. The total content of proteoglycan in GBEE was 62.6%-64.8%, which was measured by phenol sulfuric acid method and brilliant blue method. Pre-column derivatization high-performance liquid chromatography(HPLC) detection showed that the proteoglycan in GBEE contains 6 kinds of monosaccharides including mannose, rhamnose, galacturonic acid, glucose, galactose, arabinose and 14 kinds of amino acids including aspartic acid, glutamic acid, glycine,serine, threonine, alanine, proline, valine, methionine,isoleucine, leucine, phenylalanine, tryptophan and lysine.60 ICR mice, half male and half female, 6-8 weeks old and weight(18-22) g, were randomly divided into six groups: blank control group(normal saline), model group(normal saline), positive drug group( donepezi 1.25 mg·kg-1)and GBEE low-does(50 mg·kg-1), medium-does(100 mg·kg-1) and high-does(200 mg·kg-1) groups. The drug were infused to stomach of mice once a day for 14 d,after that model of learning disorder and dysmnesia were made by intraperitoneal injection of scopolamine hydrobromide(3 mg·kg-1) in six groups except the blank control group on days 15-19. Morris water maze experiment was performed by using the mice′s instinct of escaping from the water to find rest platform. The mean escape latency(s), in other words, the time needed for searching platform was detected on days 15-18, the time in platform annulus(s) was detected on day 19. Each test was performed 30 min after intraperitoneal injection and 1 h after intragastric administration. The mean escape latency(s) and the time in platform annulus(s) were correlated with the memory ability of mice, the former was negatively correlated, the latter was positively correlated, so as to evaluate the changes of learning and memory ability of each group of mice. After the behavioral experiment, the brain tissues of mice were taken out immediately, and the cerebral cortex and hippocampus were cut and stored in the refrigerator at-80℃ with the help of the mouse brain mold. During the test, the brain homogenate was prepared by ultrasonic method, and the activity of acetylcholin esterase(AChE) in the cerebral cortex and hippocampus of each group of mice was measured according to the instructions of AChE test box. RESULTS Scopolamine can significantly prolong the mean escape latency(s) of Morris water maze experiment in mice, and shorten the time in platform annulus(s), which is statistically significant compared with the control group(P<0.05,P<0.01). The results showed that scopolamine caused the decrease of learning and memory ability in the model group. The time required to search for the platform in mice of positive drug group and the GBEE of the three dose groups was significantly reduced on the third and fourth days of Morris water maze experiment test. Except for the GBEE low-dose group, the comparison with the model group was statistically significant(P<0.05, P<0.01). On day 19, positive medicine and three dose groups GBEE can significantly extend the time in platform annulus(s), compared with model group(P<0.05,P<0.01), the effect of medium-dose GBEE group is better than that of high dose, close to the positive drug, the results showed that it could improve the learning and memory ability of scopolamine-induced memory impairment modle mice. While the memory ability of the scopolamine model group was decreased, AChE activity in the cerebral cortex of the mice was significantly increased compared with the control group(P<0.05). Donepezil and GBEE in each dose could reduce Ach E activity in the cerebral cortex of the mice. Except for the high-dose GBEE group, there were significant differences between the other groups and the model group(P<0.05). The results of AChE activity in hippocampi need to be repeated further because of the large difference. CONCLUSION GBEE can improve the learning and memory ability of scopolamine induced memory impairment model mice,and the mechanism may be related to reducing the activity of cerebral AChE and reducing the inactivation of cholinergic neurotransmitter ACh in memory impairment mice.AD is a kind of neural degenerative disease, which can easily be seen in the middle-aged and old people, the early disease mainly for hypomnesis, dysmnesia and so on, accompanied by the reduction of acetylcholine(ACh), the increasing of AChE activity. Early stage of AD is the best treatment stage, by improving the memory function, which can effectively prevent the further development of AD, slow disease progression and reduce disease severity. This study shows that GBEE has certain potential in the treatment of AD, which lays a foundation for further research on the effect and mechanism of GBEE on AD.     

左旋黄皮酰胺对冈田酸和β淀粉样肽25-35神经毒性的保护作用

探讨左旋黄皮酰胺对冈田酸(okadaic acid，OA)诱导的人神经瘤细胞(SH-SY5Y)和去卵巢(ovariectomy，OVX)及单侧侧脑室注射Aβ_25-35所致神经元损伤的保护作用。通过MTT试验、LDH释放测定试验、Hoechst 33258荧光染色试验以及SH-SY5Y细胞检测，考察左旋黄皮酰胺拮抗冈田酸诱导的细胞毒作用。通过避暗试验、电镜检测、Nissl体染色及HE染色，考察左旋黄皮酰胺对去卵巢及侧脑室注射Aβ_25-35大鼠神经元的保护作用。左旋黄皮酰胺可明显拮抗冈田酸诱导的细胞毒作用，提高去卵巢及侧脑室注射Aβ_25-35大鼠的学习记忆能力，保护海马及皮层神经元。左旋黄皮酰胺可拮抗冈田酸及Aβ_25-35诱导的神经毒性，具有神经保护作用。     

依达拉奉注射液对AD大鼠学习记忆和海马内APP mRNA表达的影响

目的观察依达拉奉注射液对老年性痴呆（AD）模型大鼠学习记忆功能和海马内APP mRNA表达的影响。方法 44只大鼠随机分为空白对照组12只,造模组12只,依达拉奉低剂量干预组（干预Ⅰ组）10只,依达拉奉高剂量干预组（干预Ⅱ组）10只。用腹腔注射D-半乳糖和灌胃AlCl3法建立AD模型,从实验开始第9周开始,干预Ⅰ组和干预Ⅱ组分别于大鼠尾静脉注射依达拉奉3 mg.kg-1.d-1和6 mg.kg-1.d-1,造模组和对照组分别注射等量生理盐水。实验开始12周后以Morris水迷宫实验检测学习记忆能力,以RT-PCR法检测大鼠脑内海马APP mRNA的表达。结果依达拉奉能显著改善AD模型大鼠的学习记忆障碍（P〈0.05）,依达拉奉干预Ⅰ组和干预Ⅱ组大鼠脑内海马内APP mRNA表达的水平亦较造模组明显降低（P〈0.05）。结论依达拉奉注射液对AD模型大鼠的学习记忆障碍有明显的改善作用。     

甲基黄酮醇胺盐对大鼠学习记忆的促进作用与其抗氧化作用的关系

目的研究甲基黄酮醇胺盐对大鼠学习记忆的影响，分析该药影响学习记忆与其影响脑内自由基反应的关系。方法ｉｐ甲基黄酮醇胺盐５，１０ｍｇ·ｋｇ－１共７ｄ后，采用Ｍｏｒ－ｒｉｓ水迷宫测试大鼠的学习记忆能力，同时测定训练ｄ５和休息３０ｄ后大鼠脑内过氧化脂质（ＬＰＯ）含量和超氧化歧化酶（ＳＯＤ）活性。结果甲基黄酮醇胺盐两种剂量均可提高大鼠获取空间定位信息能力和信息贮存能力并增强记忆保持和再现过程。用药大鼠脑内ＬＰＯ含量明显低于对照组，与其记忆成绩呈正相关性。而脑内ＳＯＤ活性则高于对照组，与其记忆成绩呈负相关性。结论甲基黄酮醇胺盐对大鼠的学习记忆机能具有促进作用，而它的抗氧化作用可能为其促进学习记忆的作用机制。     

Curcumin inhibits appoptosin-induced apoptosis via upregulating heme oxygenase-1 expression in SH-SY5Y cells

Aim:

Appoptosin (SLC25A38) is a pro-apoptotic protein, which is upregulated in Alzheimer''s disease (AD) brains and plays an important role in promoting the pathological progress of AD. The aim of this study was to investigate the effects of curcumin from the rhizome of Curcuma longa on appoptosin-induced apoptosis in SH-SY5Y cells.

Methods:

SH-SY5Y cells were pretreated with curcumin, then transfected with appoptosin or vector. The apoptotic cells were detected with Annexin V staining analysis by flow cytometry. The expression of cleaved caspase-3, appoptosin, heme oxygenase-1 (HO-1) was examined using Western blotting. Intracellular level of ROS was measured with DCFH-DA staining by flow cytometry analysis. Mitochondrial membrane potential (ΔΨm) was detected with JC-1 staining under a fluorescence microscope and quantified by fluorescence ratio detection.Overexpression of appoptosin in SH-SY5Y cells markedly increased cell apoptosis accompanied by reduced HO-1 expression, increased intracellular heme level, ROS overproduction and ΔΨm impairment. Treatment of SH-SY5Y cells with curcumin (2.5–20 μmol/L) for 24 h did not significantly affect their viability. However, pretreatment with curcumin (2.5–20 μmol/L) dose-dependently attenuated all above-mentioned pathological changes in appoptosin-transfected SH-SY5Y cells.

Results:

Overexpression of appoptosin in SH-SY5Y cells markedly increased cell apoptosis accompanied by reduced HO-1 expression, increased intracellular heme level, ROS overproduction and ΔΨm impairment. Treatment of SH-SY5Y cells with curcumin (2.5–20 μmol/L) for 24 h did not significantly affect their viability. However, pretreatment with curcumin (2.5–20 μmol/L) dose-dependently attenuated all above-mentioned pathological changes in appoptosin-transfected SH-SY5Y cells.

Conclusion:

Curcumin inhibits appoptosin-induced apoptosis in SH-SY5Y cells by upregulating the expression of HO-1, reducing the production of intracellular heme and ROS, and preventing the ΔΨm loss.     

知母皂苷元及其异构体对老年大鼠学习记忆和脑内M_1受体密度的影响

目的　观察知母皂苷元 (ZMS)及其异构体 (ZMR)对老年大鼠学习记忆和脑内M1受体密度的作用。方法　选择 2 4mon龄SD老年大鼠 ,将动物分为老年对照组、ZMS组和ZMR组 ,并以 3～ 4mon龄青年大鼠作为正常对照 ,用迷宫法测定学习记忆能力 ,采用放射配基结合分析法测定脑内M1受体密度。结果　用药组大鼠连续口服ZMS和ZMR 4 0d后 ,与老年对照组比较 ,其学习记忆能力明显增强 ,脑内M1受体密度升高。结论　知母皂苷元及其异构体对老年性痴呆的胆碱能系统功能渐进性退化有一定的预防和治疗作用