目的 研究大黄素甲醚-8-O-β-D-葡萄糖苷(physcion-8-O-β-D-monoglucoside,PMG)通过 PI3K/AKT/NF-κB 信号通路干预四氯化碳(carbon tetrachloride,CCl4)急性肝损伤模型小鼠的保肝机制.方法 将小鼠随机分为正常对照组、模型组、PMG低、中、高(10、20、40 mg·kg-1)剂量组及联苯双酯(300 mg·kg-1)阳性对照组.PMG组和联苯双酯组灌胃对应药物混悬液,2次/天,连续3 d,正常对照组和模型组灌胃空白溶剂0.5％羧甲基纤维素钠(CMC-Na).末次给药1 h后,腹腔注射0.5％CCl4油溶液建立急性肝损伤模型,造模16 h后取材.给药体积均为0.1 mL/10 g体质量.HE染色法评价PMG对肝组织病理变化的改善作用;Hoechst 33342染色法检测肝细胞凋亡数;Western blot法检测肝组织中caspase-3、PI3K、p-PI3K、AKT、p-Akt、IKB、p-IKB 总蛋白及 NF-κB p65核蛋白表达水平;流式细胞术检测小鼠肝组织中辅助性T细胞17(T helper cell 17,Th17)的细胞比例.结果PMG干预可改善肝组织病理损伤程度,能明显抑制肝细胞凋亡,降低caspase-3蛋白表达水平,并能明显降低NF-κB p65核蛋白表达水平,以及PI3K、AKT、IκB蛋白磷酸化水平,降低肝组织中Th17细胞比例.结论 PMG可抑制CCl4致小鼠肝细胞凋亡,抑制肝脏过度炎症反应,其作用可能与其影响PI3K/AKT信号通路调控NF-κB激活有关.

目的 研究芍药内酯苷抗抑郁作用及其与TSPO(translocator protein 18 ku)的关系.方法 根据糖水偏好实验结果随机将小鼠分为8组:空白组、模型组(慢性不可预知应激抑郁模型)、氟西汀组,芍药内酯苷组低、中、高剂量(3.5、7.0、14.0 mg·kg-1)组、TSPO拮抗剂(PK11195)组和芍药内酯苷高剂量+PK11195组,连续给药35 d后,通过行为学实验来评估芍药内酯苷在慢性不可预知应激模型中的作用;Western blot法和ELISA法检测小鼠脑中TSPO表达量和孕酮及四氢孕酮含量,进一步明确药物作用与TSPO的关系.结果 行为学测试中,模型组与空白组均有显著性差异,说明造模成功,阳性药和芍药内酯苷不同剂量组可以逆转模型组的作用,PK11195可逆转芍药内酯苷高剂量组的作用;Western blot法和ELISA法结果显示,模型组TSPO和孕酮及四氢孕酮含量明显降低,阳性药和芍药内酯苷不同剂量组可以逆转模型组的作用,PK11195可逆转芍药内酯苷高剂量组的作用.结论 芍药内酯苷在小鼠慢性不可预知应激模型上有显著抗抑郁及抗焦虑作用,TSPO对芍药内酯苷的抗抑郁作用有一定的介导作用,这为今后进一步研究芍药内酯苷的抗抑郁作用及机制提供实验依据.

目的 观察水蜈蚣对CCL4所致小鼠急性肝损伤的保护作用,并探讨其作用机制.方法 50只雄性ICR小鼠随机分为正常组、模型组、联苯双酯组、水蜈蚣低剂量组和水蜈蚣高剂量组,各组连续13 d分别予相应溶液灌胃.末次给药后1 h,正常组按10 mL/kg腹腔注射花生油,其余4组小鼠按10 mL/kg予0.5％CCl4花生油溶液腹腔注射建立急性肝损伤小鼠模型.染毒24 h后摘眼球取血,小鼠及其肝组织称重并记录,计算小鼠肝脏指数;取肝脏组织进行HE染色,观察肝组织病理变化;分光光度法检测血清天冬氨酸氨基转移酶(GOT)、谷氨酸-丙酮酸转氨酶(GPT),肝组织超氧化物歧化酶(SOD)、丙二醛(MDA)含量,ELISA法检测血清肿瘤坏死因子-α(TNF-α)、白介素-6(IL-6)、单核细胞趋化蛋白-1(MCP-1)含量.结果 水蜈蚣24 h内给药3次后观察7 d,小鼠状态良好,未出现死亡,最大耐受量为86.4 g/kg.与正常组比较,模型组小鼠肝脏指数显著增加(P<0.01),血清GPT、GOT活力显著升高(P<0.01),HE染色呈现肝细胞大量片状坏死,伴有炎性细胞浸润,病理评分显著升高(P<0.01),肝组织SOD含量显著降低(P<0.01),MDA含量显著升高(P<0.01),血清TNF-α、IL-6、MCP-1含量均明显增加(P<0.01);与模型组比较,水蜈蚣能降低肝脏指数(P<0.05),显著降低血清GOT、GPT活性(P<0.01),明显减轻肝细胞损伤,降低病理评分(P<0.05),显著升高肝组织SOD活性(P<0.01),降低MDA含量(P<0.01),显著抑制血清TNF-α、IL-6、MCP-1含量(P<0.01,P<0.05).其作用效果与联苯双酯相当.结论 水蜈蚣对CCL4导致的急性肝损伤小鼠有显著保护作用,其作用机制可能和抑制脂质过氧化和下调炎症因子TNF-α、IL-6、MCP-1发挥抗炎作用有关.

目的:观察天王补心丸的抗抑郁作用及其对雄性大鼠性功能的影响,旨在发掘天王补心丸的作用特点.方法:通过小鼠悬尾、强迫游泳和自发活动实验验证其抗抑郁药效与5-HT1A受体的关系;通过大鼠交配行为和非接触阴茎勃起实验验证药物对雄性大鼠性功能的影响,同时加入5-HT1A受体阻断剂WAY100635探讨其可能作用机制;ELISA法检测大鼠血清雄激素水平.结果:与空白组比较,天王补心丸低、中、高剂量组,氟西汀组,天王补心丸+WAY100635组小鼠悬尾不动时间显著降低(P＜0.05,P＜0.01),天王补心丸中、高剂量组,氟西汀组及天王补心丸+WAY100635组小鼠强迫游泳不动时间显著降低(P＜0.05),说明天王补心丸有显著的抗抑郁作用,且与5-HT1A受体无关.在大鼠性功能实验中,与空白组比较,氟西汀组雄性大鼠爬垮潜伏期、插入潜伏期和射精间歇时间显著延长(P＜0.01),爬垮次数、插入次数和射精次数显著减少(P＜0.01),阴茎勃起次数也显著减少(P＜0.01),而天王补心丸无此作用,合用WAY100635后氟西汀的性功能障碍作用消失;同时,所有药物对大鼠雄激素均无显著性影响.结论:天王补心丸的抗抑郁作用可能与5-HT1A受体无关,且对雄性大鼠性功能没有影响,优于氟西汀.

目的:研究天王补心丸对慢性应激抑郁模型小鼠行为学、下丘脑-垂体-肾上腺轴(HPA轴),海马糖原合酶激酶3β(GSK3β)磷酸化及脑源性神经营养因子(BDNF)表达的影响,初步探讨其抗抑郁作用机制.方法:将60只雄性ICR小鼠按照糖水偏嗜度随机分为正常组、慢性应激模型组、盐酸氟西汀组(10 mg·kg-1)以及天王补心丸高、中、低剂量组(3.6,1.8,0.9 g·kg-1).采用慢性不可预知应激实验(CUS)建立抑郁症小鼠模型,各给药组灌胃给药28 d后通过糖水偏好实验、开场行为实验、新奇抑制摄食实验检测其行为学变化.之后分别取小鼠血、肾上腺及海马组织,采用酶联免疫吸附测定(ELISA)法检测小鼠血清中促肾上腺皮质激素(ACTH)和皮质酮(CORT)含量,蛋白免疫印迹法(Western blot)检测海马组织中GSK3β磷酸化及BDNF表达的变化,并计算肾上腺指数.结果:与正常组比较,模型组小鼠的蔗糖水偏嗜度显著降低(P＜0.01),开场活动次数明显减少(P＜0.05),新奇抑制摄食潜伏期延长(P＜0.01),血清ACTH,CORT含量民明显升高(P＜0.05,P＜0.01),海马组织中GSK3β磷酸化及BDNF表达显著降低(P＜0.01),肾上腺指数显著升高(P＜0.01);与模型组比较,天王补心丸可以逆转抑郁症模型小鼠行为学变化(P＜0.05,P＜0.01),显著降低抑郁症模型小鼠血浆ACTH和CORT的含量(P＜0.01)和肾上腺指数(P＜0.01),同时增加小鼠海马GSK3β磷酸化及BDNF表达水平(P＜0.05,P＜0.01),其作用效果与盐酸氟西汀相当.结论:天王补心丸对慢性不可预知应激抑郁模型小鼠具有显著的抗抑郁作用,其作用机制与抑制HPA轴活性、上调海马GSK3β磷酸化及BDNF的蛋白表达有关.

This study aimed to investigate the antidepressant effects of Puyu Capsules and its potential mechanism. The antidepressant activity of Puyu Capsules was evaluated by forced swimming test(FST) and tail suspension test(TST) after subchronic administration in mice. Next, the mice were subjected to a chronic unpredictable stress(CUS) protocol for a period of 28 d to induce depressive-like behaviors. Then, a sucrose preference test, open-field test and novelty-suppressed feeding test were performed to evaluate the antidepressant effect of Puyu Capsules. After the behavioral test, the adrenal index was calculated; the levels of serum corticosterone(CORT) and adrenocorticotropic hormone(ACTH) were detected by enzyme-linked immunosorbent assay(ELISA); the levels of glucocorticoid receptor(GR), protein expression of brain-derived neurotrophic factor(BDNF), and the ratio of phosphorylated cAMP response element binding protein(CREB) to total CREB were detected by Western blot to explore the antidepressant function and mechanism of Puyu Capsules. The results suggested that Puyu Capsules had significant antidepressant effects on both the depression model and CUS model. At the same time, the drug could prevent the change of adrenal index induced by CUS and reverse the abnormal activation of CORT and ACTH in the serum of depressed mice. Finally, Puyu Capsules could also reverse the lower expression of pCREB, BDNF and GR in the hippocampus of CUS mice. In conclusion, Puyu Capsules produced significant antidepressant effects, and the mechanism was closely related to hypothalamic pituitary adrenal(HPA) axis activity, GR and CREB-BDNF pathway expression.

Objective:To observe the impacts of Jieyu capsule (Puyu capsule) on mice of drug-induced depression model and the possible mechanism of action.Methods:The mice were divided randomly into control group,imipramine group,Jieyu capsule (Puyu capsule) low-dosage group (235 mg · kg-1),Jieyu capsule(Puyu capsule) medium-dosage group (470 mg · kg-1) and Jieyu capsule(Puyu capsule) high-dosage group(940 mg · kg-1) according to body weights.A reserpine-induced depression model was produced through reserpine antagonism experiment,and the impacts of Jieyu capsule (Puyu capsule) on reserpine-induced body temperature drop,acinesia and ptosis were observed;then the times of mice twitching heads and fatality rate caused by yohimbine were observed through serotonine-induced head twitching experiment and yohimbine toxicity experiment,and also the impacts of drugs on serotonine and norepinephrine in mouse body were observed.Results:After being injected with reserpine,animals were reserpinized,i.e.,subjected to body temperature drop,acinesia and ptosis;Jieyu capsule of different dosages could antagonize its actions remarkably.In serotonine-induced head twitching experiment,it was observed that the times of head twitching of the mice taking Jieyu capsule(Puyu capsule) hadn't increased remarkably.In yohimbine toxicity experiment,it was observed that the mediumdosage and high-dosage Jieyu capsule(Puyu capsule) could both add yohimbine's toxicity.Conclusion:Jieyu capsule (Puyu capsule) has the anti-depression effect on reserpine-induced depression model mice;its mechanism of action is likely to be related to the enhancement of neurologic function of norepinephrine in the brain.

目的:观察四物汤对血虚证小鼠肝细胞凋亡执行分子Caspase 8 mRNA表达的影响.方法:24只C57BL/6J小鼠随机分为空白组、模型组、给药组.以腹腔注射环磷酰胺建立血虚证模型,采用全自动血液分析仪检测外周血象,TUNEL法检测肝细胞凋亡百分率,荧光定量PCR法检测Caspase 8 mRNA表达.结果:与模型组相比,给药组小鼠外周血红细胞数及血红蛋白含量升高(P<0.05),肝细胞凋亡百分率下降(P<0.05),Caspase 8 mRNA表达水平下降(P<0.05).结论:四物汤可改善血虚证模型小鼠外周血象,下调凋亡执行分子Caspase 8 mRNA表达,减少肝细胞凋亡.提示四物汤减少血虚证模型肝细胞凋亡的作用机制可能与其抑制Caspase 8激活有关.

目的 从解郁合欢汤、血府逐瘀汤和天王补心丹3种复方水煎剂中初步筛选出有潜在抗抑郁效果的复方. 方法 取健康SPF级雄性KM小鼠50只,根据旷场试验结果随机分成空白组、盐酸氟西汀组、解郁合欢汤组、血府逐瘀汤组和天王补心丹组5组,每日灌胃给药1次,连续给药14d.每周进行悬尾试验、强迫游泳试验观测小鼠行为学变化;给药结束后测定小鼠自发活动;行为学试验结束后,用Western Blot法测定小鼠海马p-GSK3β的表达量. 结果 ①与空白组相比,血府逐瘀汤组和天王补心丹组在给药第1周和第2周均能显著缩短小鼠悬尾和游泳不动时间,作用与盐酸氟西汀组相当,其中天王补心丹组作用最显著;解郁合欢汤组有作用趋势,但无显著性差异.②3种复方均不影响小鼠自发活动.③3种复方均能增加小鼠海马p-GSK3β的表达量,天王补心丹组作用最显著. 结论 天王补心丹抗抑郁效果较强,其作用机制可能与增加海马p-GSK3β的表达有关.

目的 观察四物汤对血虚证小鼠肝细胞凋亡相关分子Caspase3及Caspase8表达的影响.方法 24只C57BL/6J小鼠随机分为空白组、模型组、给药组.以腹腔注射环磷酰胺建立血虚证模型,采用全自动血液分析仪检测外周血象,TUNEL法检测肝细胞凋亡百分率,荧光定量PCR法检测Caspase3及Caspase8 mRNA表达.Western blot检测Caspase3及Caspase8蛋白表达.结果 与模型组相比,给药组小鼠外周血红细胞数及血红蛋白含量升高(P＜0.01),肝细胞凋亡百分率下降(P＜0.01),Caspase3及Caspase8 mRNA及蛋白表达水平下降(P＜0.05,P＜0.01).结论 四物汤可改善血虚证模型小鼠外周血象,下调凋亡相关分子Caspase3及Caspase8表达,减少肝细胞凋亡.提示四物汤减少血虚证模型肝细胞凋亡的作用机制可能与其抑制Caspase3及Caspase8激活.

目的：观察菖郁通络颗粒治疗缺血性中风后轻度认知功能障碍（MCI）的临床疗效。方法将确诊为缺血性中风后所致轻度认知功能障碍患者80例，根据不同的治疗方案将患者平均分为西药组和结合组。2组患者均常规给予抑制血小板聚集、控制血压、血脂、血糖、改善脑部血液循环及健康教育等综合治疗，西药组给于尼莫地平普通片，每次40 mg，每天3次，饭后口服治疗，结合组在此基础上加用菖郁通络颗粒，每天3次，每次1包，饭后口服治疗。两组治疗6个月，评估患者治疗前后蒙特利尔量表（ MoCA）、日常生活能力量表（ ADL）变化、血液流变学变化情况。结果结合组与西药组在治疗第6个月对MoCA进行组间比较，P＜0.05，ADL评分进行组间比较，P＜0.05，治疗后结合组与西药组的血液流变学比较，P＜0.05，均有统计学意义。结论菖郁通络颗粒治疗缺血性中风后轻度认知功能障碍具有显著疗效，可缓解患者认知功能，延缓痴呆形成。

目的 探讨解郁散乙酸乙酯和正丁醇有效部位的抗抑郁作用及其机制,为解郁散的进一步开发应用提供实验依据和理论基础. 方法 选择80只昆明种小鼠随机分为溶剂组、盐酸丙咪嗪组、正丁醇提取物高、中、低剂量组,乙酸乙酯提取物高、中、低剂量组共8组,每组各10只.采用小鼠悬尾试验、强迫游泳试验初步检测正丁醇提取物和乙酸乙酯提取物的抗抑郁效应,再通过5-HTP诱导的小鼠甩头试验和育亨宾毒性试验初步揭示其抗抑郁机制. 结果 小鼠悬尾不动时间和强迫游泳不动时间表明解郁散正丁醇低剂量组和乙酸乙酯高剂量组都有明显抗抑郁作用;5-HTP诱导小鼠甩头试验和育亨宾毒性试验结果发现两者均能增加小鼠甩头次数和增加育亨宾的致死率,其中正丁醇提取物和乙酸乙酯提取物中、高剂量组能明显增多小鼠甩头次数;同时,乙酸乙酯提取物均可以增加育亨宾的致死率,而正丁醇提取物中剂量组无此作用. 结论 解郁散乙酸乙酯提取物和正丁醇提取物都有抗抑郁作用,均增加了小鼠甩头次数和育亨宾毒性,说明其作用机制可能与增加突触间隙单胺递质有关.从量效关系来看:乙酸乙酯提取物的量效关系更好.

Objective To study the analgesic effect and the drug-receptor interactions with frog rectus abdominis N2-receptor of the neurotoxin from Naja atra venom( NT). Methods Three model of pain( tail electric stimulation-vocali-zation test ,the hot-plate test ,and writhing responses in mice)were used. The effects of NT on acetylcholine-induced i-solated frog rectus abdoninis were observed. Results NT could dose-dependently raise the pain threshold in hot-plate test in mice and inhibit the writhing reaction induce by acetic acid in mice . The analgesic effect of NT effect at 2 h and peaked at 5 h. NT produced a concentration-dependent parallel shift to the right of dose-response curve of acetylcholine applied exogenously with no change in the maximal asymptotic response. Conclusion NT had a better analgesic effect on the pain due to hot- plate ,acetic acid and electric stimulation. NT was determined as the competitive antagonists of N2 -AChR.

Objective: To compare the analgesia and anti-inflammatory effects of contents from Tougu Xiaotong Prescription which extracted by different methods and determine the best one.Method: Using the method of acetic acid-induced writhing in mice to observe the effects strength of analgesia from Tougu Xiaotong prescription 1 to 4,the best prescription was determined.Then,the best prescription were divided into low,medium and high dose groups,and the methods of acetic acid-induced writhing and xylene-induced ear swelling in mice were used to observe the anti-inflammation and analgesia effects from three dose groups.Results: Tougu Xiaotong prescription 2 and 3 can reduce the times of acetic acid-induced writhing in mice and the latter was the best.The medium and high dose groups of prescription 3 can significantly reduce the times of acetic acid-induced writhing,and inhibit the xylene-induced ear swelling in mice.Conclusion: The Tougu Xiaotong prescription 3 has a significant anti-inflammation and analgesia effects,which may serve as the raw material for new capsule.

<正>解郁散是著名中医学家施奠邦教授的经验方,临床疗效显著,长期服用未见明显毒副作用。解郁散由四逆散加味而成,由柴胡、枳实、白芍、炙甘草、合欢花组成。前期研究表明解郁散对慢性应激抑郁大鼠模型有抗抑郁作用,对抑郁大鼠行为