咔唑类生物碱衍生物CZ-7对cuprizone诱导的动物模型髓鞘再生的影响及机制

目的研究咔唑类生物碱衍生物CZ-7对cuprizone(CPZ)诱导的小鼠模型髓鞘再生的影响及相关作用机制。方法对C57BL/6J小鼠采用灌胃CPZ 4周诱导髓鞘脱失的实验动物模型,并同时给予CZ-7进行治疗。采用行为学、LFB染色法及QPCR检测CZ-7对髓鞘损伤的保护作用;采用免疫荧光染色及油红O染色法观察CZ-7对有害髓鞘碎片的清除作用;采用免疫荧光化学染色法检测CZ-7对小胶质细胞吞噬作用的影响。结果与对照组相比,CPZ组小鼠出现明显的行为运动障碍,CZ-7对CPZ小鼠的行为学障碍有改善作用;CPZ能够诱导C57BL/6J小鼠胼胝体区域出现广泛的髓鞘脱失且髓鞘相关基因的表达明显减少,而CZ-7对CPZ诱导的髓鞘损伤有保护作用(P<0.05,P<0.01);CZ-7可以促进CPZ小鼠胼胝体部位有害髓鞘碎片的清除(P<0.01);给予CZ-7后,更多的吞噬样小胶质细胞被募集到胼胝体部位吞噬髓鞘碎片,有利于髓鞘再生。结论 CZ-7能够显著减轻CPZ诱导的髓鞘损伤,促进髓鞘再生。其作用机制可能是通过增强小胶质细胞的吞噬作用,促进有害髓鞘碎片的清除来实现的。     

原花青素B2在双环己酮草酰二腙诱导脱髓鞘模型中调节铁代谢和减轻氧化应激促进髓鞘再生作用机制研究

目的:探究原花青素B2(proanthocyanidins B2,PC-B2)促进双环己酮草酰二腙(cuprizone, CPZ)诱导的小鼠脱髓鞘模型髓鞘再生的作用机制。方法:选用40只C57BL/6雄性小鼠,随机分为4组,给予0.2%(质量分数)的CPZ构建脱髓鞘小鼠模型;采用旷场、T迷宫和高架十字迷宫观察小鼠行为学变化;通过固蓝染色(luxol fast blue, LFB)和免疫荧光染色观察胼胝体区域髓鞘、髓鞘碱性蛋白(myelin basic protein, MBP)、降解髓鞘碱性蛋白(degraded myelin basic protein, dMBP)、腺瘤样息肉抗体(adenomatous polyposis coli, CC1)、铁蛋白(ferritin)、胶质纤维酸性蛋白(glial fibrillary acidic protein, GFAP)、离子化钙结合适配分子1(ionized calcium binding adapter molecule 1,Iba1)的变化;采用ELISA法检测脑匀浆中过氧化氢酶(catalase, CAT)、丙二醛(malond...     

血竭提取物对急性心衰大鼠脑缺血耐受的作用研究

目的 研究血竭提取物对大鼠急性心力衰竭（acute heart failure,AHF）致脑功能损伤的保护作用及其机制。方法 将25只SD大鼠随机分为空白对照组、心衰模型组和血竭提取物干预组。空白对照组和心衰模型组每日生理盐水灌胃,干预组按照血竭提取物浓度分为低剂量（300 mg·kg^-1·d^-1）、中剂量（450 mg·kg^-1·d^-1）和高剂量（600 mg·kg^-1·d^-1）3组,每日灌胃。采用Morris水迷宫检测大鼠的空间学习记忆能力的变化;检测超氧化物歧化酶（superoxide dismutase,SOD）活性及丙二醛（malondialdehyde,MDA）含量;HE染色观察脑组织病理变化。结果 Morris水迷宫试验中,空白对照组和血竭提取物高、中剂量组的逃避潜伏期均短于心衰模型组,运动平均速度和目标象限时间百分比均大于心衰模型组;心衰模型组的MDA含量较空白对照组增加,SOD活性反之;血竭提取物干预组的MDA含量较心衰模型组下降,SOD活性反之。结论 急性心力衰竭单次发作即可损伤脑功能,血竭提取物可能通过抗氧化和清除氧自由基等对防治大鼠急性心力衰竭所致的脑功能损伤具有积极的保护作用。     

依达拉奉对脑梗死大鼠神经髓鞘再生、认知功能及VEGF/Notch1信号通路的影响

目的 探讨依达拉奉对脑梗死大鼠神经髓鞘再生、认知功能及血管内皮生长因子（VEGF）/跨膜体受体蛋白（Notch1）信号通路的影响。方法 50只大鼠按照随机数字表法分为对照组、模型组、阿司匹林组和依达拉奉1.5、3 mg/kg组，每组10只。除对照组外，其余组大鼠均建立大脑中动脉梗死模型，依达拉奉1.5、3mg/kg组分别尾iv依达拉奉注射液，阿司匹林组注射4 mg/kg阿司匹林溶液。穿梭箱联合水迷宫实验观察各组大鼠认知功能；ELISA法检测各组大鼠血清髓鞘碱性蛋白（MBP）含量；Pal-Weigert染色观察各组大鼠神经髓鞘形态；TTC染色测定各组大鼠脑梗死体积；免疫印迹法检测各组大鼠VEGF/Notch1水平。结果 与模型组比较，依达拉奉各剂量组能够主动逃避次数增加，被电次数、学习和记忆潜伏时间减少（P＜0.05）；与模型组比较，依达拉奉各剂量组血清MBP含量、梗死体积、Notch1水平下降，VEGF水平升高（P＜0.05）。模型组髓鞘崩解、破坏、脱失严重，髓鞘稀疏，部分区域有髓鞘断裂缺失，染色变浅；依达拉奉各剂量组及阿司匹林组髓鞘形态改善。结论 依达拉奉可促进VEGF活性，抑制炎症反应，调控Notch1信号通路，降低MBP蛋白表达，促进神经髓鞘再生，提升认知功能。     

抗炎抗凝融合蛋白TAP-SSL5对ApoE基因敲除小鼠动脉粥样硬化病变形成的影响

摘 要 目的：探讨重组融合蛋白蜱抗凝血肽（TAP） 金黄色葡萄球菌超抗原样蛋白5（SSL5）对ApoE基因敲除（ApoE-/-）小鼠动脉粥样硬化病变形成的影响。方法: 选取12周龄雄性ApoE-/-小鼠21只,随机分为3组：TAP-SSL5组（3 mg·kg^-1·d^-1）、SSL5组（2 mg·kg^-1·d^-1）、空白对照组（pH 7.4磷酸盐缓冲液）,ip,qd,连续给药12周,观察小鼠体质量变化。高脂饮食饲养12周后取材,检测血浆总胆固醇（TC）、三酰甘油（TG）、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)水平;对小鼠主动脉血管进行石蜡切片,常规HE染色,分析小鼠主动脉根部血管动脉粥样硬化斑块的形成情况,小鼠主动脉内膜面采用油红O染色,比较动脉粥样硬化斑块的分布情况。结果: 高脂饲养12周后,与空白对照组比较,TAP-SSL5组小鼠体质量增长和TC水平明显降低（P<0.001）,而TG、HDL-C、LDL-C水平无明显变化。HE染色结果表明,TAP-SSL5组主动脉根部切片斑块面积明显降低（P<0.05）;主动脉大体标本斑块油红O染色提示TAP-SSL5干预组主动脉动脉粥样硬化斑块形成明显小于空白对照组。结论:TAP-SSL5可显著抑制ApoE-/-小鼠动脉血管粥样硬化斑块的形成。     

雌激素对实验性自身免疫性脑脊髓炎小鼠治疗作用的观察

目的:探讨雌激素对实验性自身免疫性脑脊髓炎(EAE)小鼠中枢神经系统(CNS)髓鞘及轴突损伤的影响。方法:用MOG35-55多肽诱发建立40只EAE小鼠模型后随机分为2组,各20只,治疗组予雌激素治疗,对照组予同等量的生理盐水灌胃处理。比较2组EAE小鼠的临床症状评分和体质量变化。取各组EAE小鼠脑和脊髓,行罗克沙尔固蓝(LFB)-HE染色及Bielschowsky染色观察髓鞘及轴突损伤情况;实时荧光定量PCR及Westernblot检测各组EAE小鼠CNS中髓鞘碱性蛋白(MBP)及生长相关蛋白-43(GAP-43)的表达。结果:治疗组EAE小鼠较对照组临床症状评分、平均丧失的最大体质量降低;LFB-HE染色、Bielschowsky染色示治疗组较对照组脱髓鞘减轻,轴突损伤减轻,PCR及Westernblot结果显示治疗组MBP和GAP-43表达较对照组增加。结论:雌激素可通过减轻髓鞘损伤及促进轴突再生治疗EAE小鼠。     

构树总黄酮对免疫抑制小鼠免疫功能的影响

目的 探讨构树总黄酮（total flavonoids of Broussonetia papyrifera,TFBP）对环磷酰胺诱导的免疫抑制小鼠免疫功能的影响。方法 用环磷酰胺复制免疫抑制模型并随机分为模型组、构树总黄酮高、中、低剂量组（200,100,50 mg·kg^-1·d^-1）,以正常小鼠为空白对照组。分别于饲喂构树总黄酮后第10天和第30天采样,检测白细胞含量、腹腔巨细胞吞噬功能、T、B淋巴细胞转化率、血清IgG含量及BSA抗体水平。结果 与模型组比较,饲喂TFBP的高、中、低剂量组小鼠的白细胞含量、腹腔巨噬细胞吞噬功能、T、B淋巴细胞转化率、BSA抗体水平和血清IgG均显著升高（P < 0.05或P < 0.01）,随着TFBP剂量的增加,上述免疫指标与空白对照组相近。结论 构树总黄酮能显著改善环磷酰胺诱导的免疫抑制小鼠的免疫功能。     

乌苯美司对慢性阻塞性肺疾病小鼠免疫失衡及氧化应激的影响

目的 研究乌苯美司对慢性阻塞性肺疾病（chronic obstructive pulmonary disease,COPD）小鼠免疫失衡及氧化应激的影响。方法 50只小鼠随机分为空白组、模型组、乌苯美司组、氨茶碱+吸氧组、氨茶碱+吸氧+乌苯美司组,共5组。空白组不做处理,其余4组均诱导建立COPD小鼠模型,造模第8天开始,乌苯美司组以20 mg·kg^-1乌苯美司灌胃治疗;氨茶碱+吸氧组采用吸氧、氨茶碱溶液（10 mL·kg^-1）灌胃常规治疗;氨茶碱+吸氧+乌苯美司组在氨茶碱+吸氧组基础上加以20 mg·kg^-1灌胃乌苯美司治疗;空白组、模型组予以同等剂量的生理盐水,连续给药4周,采用Buxco系统检测小鼠肺功能吸气峰流量（peak inspiratory flow,PIF）、呼气峰流量（peak expiratory flow,PEF）、每分钟通气量（minute volume,MV）后处死小鼠,采血样及肺组织样本。HE染色考察肺组织病理学变化;流式细胞测定全血CD3⁺、CD4⁺、CD8⁺水平,并计算CD4⁺/CD8⁺;ELISA检测血清MDA、SOD、IL-8、TNF-α、CRP水平。结果 与模型组相比,乌苯美司组、氨茶碱+吸氧组、氨茶碱+吸氧+乌苯美司组病理损伤明显减轻;氨茶碱+吸氧+乌苯美司组PIF、PEF、MV及CD3⁺、CD4⁺、CD4⁺/CD8⁺水平明显升高（P<0.01）,CD8⁺水平明显降低（P<0.05）;仅氨茶碱+吸氧+乌苯美司组较模型组MDA、SOD、TNF-α、IL-8、CRP含量均明显改善（P<0.01）。结论 乌苯美司辅助常规治疗能有效改善COPD小鼠肺功能及免疫水平,减轻炎症反应和调节氧化应激,促进肺组织明显恢复。     

补肝散不同分离组份抗抑郁活性筛选

目的 对补肝散醇提物不同分离组份的抗抑郁活性进行筛选。方法 采用慢性不可预知温和应激（chronicunpredictable mild stress,CUMS）对小鼠进行为期8周的造模,造模4周后,分别以盐酸帕罗西汀（paroxetine hydrochloride,PX）、补肝散醇提物、石油醚（A）、二氯甲烷（B）、乙酸乙酯（C）及正丁醇（D）4个分离组份进行为期4周的灌胃治疗,考察各组小鼠的行为学及脑内神经递质含量的变化。结果 连续给药4周（造模8周）后,PX组（0.026 g·kg^-1）、补肝散醇提物组（1.92 g·kg^-1）及其分离组份C（0.232 g·kg^-1）、D（1.04 g·kg^-1）和B（0.160 g·kg^-1）组均能明显逆转模型小鼠的抑郁表现如糖水偏好率下降、强迫游泳不动时间延长等抑郁症状。能不同程度地增加其脑内额叶皮质中5-羟色胺和多巴胺的含量,其中PX、醇提物及分离组份C的作用更为明显（与模型组比较,P<0.05或<0.01）。结论 补肝散醇提物的抗抑郁活性部位主要集中于乙酸乙酯和正丁醇分离组份,其次是二氯甲烷分离组份。     

苦参素胶囊对BALB/c小鼠人肝癌细胞株SMMC 7721体外种植瘤的影响

摘 要 目的：观察苦参素胶囊对BALB/c小鼠人肝癌细胞株SMMC 7721体外种植瘤的影响。方法: 采用体外传代培养人肝癌SMMC 7721细胞株,建立体外种植瘤小鼠肝癌模型。随机分为模型组、氟尿嘧啶（5 Fu）组（25 mg·kg^-1）、苦参素胶囊高剂量组（90 mg·kg^-1）、苦参素胶囊低剂量组（45 mg·kg^-1）,另设空白对照组。每组10只,连续给药14 d后。眼球取血,分离血清,Elisa法测定IL 2水平。摘取瘤株,称量湿质量,计算抑制率;HE染色,观察肿瘤组织的病理改变。结果: 与模型组比较,苦参素胶囊高、低剂量组可显著升高小鼠血清IL 2含量（P<0.01或P<0.05）;抑制体外种植瘤生长（P<0.001或P<0.05）;高剂量组上述作用与5 Fu组相比无明显差异（P>0.05）。HE染色可见小鼠肿瘤细胞核染色变浅,肿瘤细胞数量减少。结论: 苦参素胶囊对BALB/c小鼠人肝癌细胞株体外种植瘤有一定的抑制作用。     

Protective and therapeutic role of Bilobalide in cuprizone-induced demyelination

Multiple sclerosis (MS) is a chronic demyelinating disease of the central nervous system characterized by recurrent and progressive demyelination, neuroinflammation and oligodendrocyte loss. The cuprizone (CPZ) model is characterized by primary and reversible demyelination, accompanied by oligodendrocyte loss and neuroinflammation. In the current study, we explored the efficiency of Bilobalide in the demyelination and remyelination. The results demonstrate that Bilobalide improved behavioral abnormality and promoted remyelination in the corpus callosum by using Luxol Fast Blue, Black Gold II and myelin basic protein (MBP) staining. We for the first time found that CPZ caused the splenic atrophy and induced the formation of myelin oligodendrocyte glycoprotein (MOG) antibody, which was attenuated by Bilobalide. Thus, Bilobalide decreased the loss of O4+ oligodendrocytes possibly through MOG antibody-dependent cell cytotoxicity. Bilobalide also prevented the infiltration of CD4⁺ T cells, CD68⁺ macrophages and B220⁺ B cells within the brain, and reduced the inflammatory microenvironment mediated with Iba1⁺iNOS⁺ and Iba1⁺NF-kB⁺ microglia after CPZ challenge, accompanied by the inhibition of IL-1β and IL-6 in the brain. These results identify a potent therapeutic efficiency for Bilobalide and highlight clear pleiotropic effects of the compound beyond specific autoantibody and inflammatory microenvironment in CPZ-mediated demyelination.     

虎杖清脉饮对慢性脑缺血小鼠认知功能及肠道菌群的影响

目的 从肠道菌群角度探讨虎杖清脉饮对慢性脑缺血小鼠认知功能改善的作用机制。方法 放置微弹簧圈于双侧颈总动脉致狭窄制备慢性脑缺血小鼠模型。灌胃给药12 w后,采用Morris水迷宫和LFB染色测定小鼠的认知功能和白质的损伤程度;提取各组小鼠盲肠内容物,进行16S rRNA基因V3+V4去扩增子信息采集与分析。结果 水迷宫实验结果显示,虎杖清脉饮组小鼠逃避潜伏期显著缩短,跨越平台次数和目标象限百分比增加,学习记忆功能明显改善。LFB染色显示,模型组白质损伤严重;虎杖清脉饮组白质损伤程度较轻。16S rRNA测序结果显示,与模型组相比,虎杖清脉饮组小鼠肠道菌群中疣微菌门、阿克曼菌属和丹毒荚膜菌属的丰度显著降低（P<0.05）,而嗜木聚糖真杆菌属和异杆菌属的丰度显著增加（P<0.05）。结论 虎杖清脉饮具有改善慢性脑缺血小鼠认知功能的作用,其保护作用可能与调节慢性脑缺血小鼠肠道菌群有关。     

Treatment with the anti-diabetic drug metformin ameliorates betel-nut induced carcinogenesis in a murine model

BackgroundMetformin, a widely used anti-diabetic drug has gained enormous attention as an anticancer agent. This study seeks to investigate the efficacy of metformin in ameliorating aqueous extract of betel-nut (AEBN) and arecoline induced carcinogenesis in a murine model.MethodsSwiss albino mice were exposed to AEBN (2 mg ml⁻¹) and arecoline (10 μg ml⁻¹) in drinking water for 16 weeks followed by co-administration of metformin (75 mg kg⁻¹ or 150 mg kg⁻¹) for 4 or 8 weeks. Histological changes and oxidative stress were assessed by haematoxylin and eosin staining, TBARS assay and protein carbonylation assay respectively. Lipid profile was determined using an automated analyzer. Expression of total and phosphorylated AMPK, ACC and p53 were determined by immunoblotting.ResultsAEBN and arecoline induced dyslipidemia by downregulating AMPK (Thr-172) and activating ACC (Ser-79); they also downregulated tumor suppressor p53 (Ser-15). Metformin treatment induced AMPK-dependent alleviation of dyslipidemia in a dose and time dependent manner, upregulated p53 (Ser-15), restored tissue architecture and reduced oxidative stress in tissues of AEBN and arecoline treated mice.ConclusionThis study establishes that betel nut induces dyslipidemia through its alkaloid, arecoline by inhibition of AMPK (Thr-172) and activation of ACC (Ser-79) and highlights the therapeutic potential of metformin for treatment of betel-nut induced carcinogenesis, indicating the repurposing of the old drug in a new avenue.     

Toxicity of cuprizone a Cu2+ chelating agent on isolated mouse brain mitochondria: a justification for demyelination and subsequent behavioral dysfunction

Multiple Sclerosis (MS) is a complex disease with an unknown etiology and no effective cure, despite decades of extensive research that led to the development of several partially effective treatments. In this study we aimed to investigate brain mitochondrial dysfunction in demyelination induced by cuprizone in mice. Cuprizone was used for induction of demyelination in mice through a diet containing 0.2% w/w cuprizone for 5 weeks. Behavioral tests for proving of MS was performed and then mitochondria from brain of animals were isolated and afterwards parameters of mitochondrial dysfunction examined. Results of mitochondrial dysfunction parameters such as mitochondrial swelling, production ROS, collapse of the membrane potential showed that isolated mitochondria from cuprizone treated mice have been damaged compared to those of untreated control mice. It is likely that demyelination induced mitochondrial damage led to increased mitochondrial ROS formation and progression of oxidative damages in neurons. It is suggested that cuprizone which is a Cu²⁺?chelating agent causes impairment of electron transport chain (complex IV) and antioxidant system (SOD) in mitochondria leading to decreased ATP production and increased ROS formation.     

Neuroprotective effects of ellagic acid on cuprizone-induced acute demyelination through limitation of microgliosis,adjustment of CXCL12/IL-17/IL-11 axis and restriction of mature oligodendrocytes apoptosis

Context: Ellagic acid (EA) is a natural phenol antioxidant with various therapeutic activities. However, the efficacy of EA has not been examined in neuropathologic conditions.

Objective: In vivo neuroprotective effects of EA on cuprizone (cup)-induced demyelination were evaluated.

Material and methods: C57BL/6?J mice were fed with chow containing 0.2% cup for 4?weeks to induce oligodendrocytes (OLGs) depletion predominantly in the corpus callosum (CC). EA was administered at different doses (40 or 80?mg/kg body weight/day/i.p.) from the first day of cup diet. Oligodendrocytes apoptosis [TUNEL assay and myelin oligodendrocyte glycoprotein (MOG⁺)/caspase-3⁺ cells), gliosis (H&;E staining, glial fibrillary acidic protein (GFAP⁺) and macrophage-3 (Mac-3⁺) cells) and inflammatory markers (interleukin 17 (IL-17), interleukin 11 (IL-11) and stromal cell-derived factor 1 α (SDF-1α) or CXCL12] during cup intoxication were examined.

Results: High dose of EA (EA-80) increased mature oligodendrocytes population (MOG⁺ cells, p?p?+ cells, p?+ cells) compared with the cup mice.

Discussion and conclusion: In this model, EA-80 effectively reduces lesions via reduction of neuroinflammation and toxic effects of cup on mature OLGs. EA is a suitable therapeutic agent for moderate brain damage in neurodegenerative diseases such as multiple sclerosis.     

DHF-7 Ameliorates Behavioral Disorders and White Matter Lesions by Regulating BDNF and Fyn in a Mouse Model of Schizophrenia Induced by Cuprizone and MK-801

BackgroundSchizophrenia is a psychiatric disorder including multiple clinical symptoms such as severe psychosis and cognitive dysfunction. DHF-7 is a novel dihydroflavanone derivative that was designed and synthesized to treat schizophrenia. This study aimed to investigate the effects and mechanisms of DHF-7 in a mouse model of schizophrenia induced by a combination of cuprizone and MK-801.MethodsAfter intragastric administration of DHF-7 for 7 weeks, open field, Y-maze, and novel object recognition tests were performed to detect behavioral changes in the mouse model. White matter lesions and myelin loss were determined using transmission electron microscopy and oil red O staining. Western blotting and immunohistochemistry were used to detect the expression of the related proteins.ResultsThe results showed that DHF-7 treatment significantly improved cognitive impairment and positive symptoms in the model mice. Moreover, DHF-7 alleviated white matter lesions and demyelination and promoted the differentiation and maturation of oligodendrocytes for remyelination in the corpus callosum of model mice. The mechanistic study showed that DHF-7 increased the expression of brain-derived neurotrophic factor and phosphorylated Fyn, thus activating the tyrosine kinase receptor B (Trk B)/Fyn/N-methyl-D-aspartate receptor subunit 2 B (NMDAR2B) and Raf/mitogen-activated protein kinase (MEK)/ extracellular signal-related kinase (ERK) signaling pathways.ConclusionsOur results provide an experimental basis for the development of DHF-7 as a novel therapeutic agent for schizophrenia.     

白藜芦醇抑制角蛋白17改善银屑病样皮肤损伤

目的 探讨白藜芦醇（Rsv）对咪喹莫特（IMQ）诱导的银屑病样皮肤损伤的改善作用及其作用机制。方法 BALB/c小鼠随机分为4组：对照组、Rsv组、模型（IMQ）组、Rsv治疗（IMQ+Rsv）组,每组6只;涂抹IMQ诱导BALB/c鼠耳部银屑病样皮肤损伤模型,连续8 d,同时涂抹20 mg Rsv予以治疗;观察红斑及银屑的多少、游标卡尺测量耳厚度;HE染色观察组织改变;实时荧光定量（qRT-PCR）检测组织角蛋白17（K17）、IL-17A、IL-19及IL-23 mRNA表达;Western blotting检测K17蛋白表达。结果 与模型组比较,Rsv治疗组小鼠红斑面积明显减少,表皮鳞屑减少,耳缘厚度显著降低;HE染色结果表明,Rsv治疗组耳缘组织表皮厚度明显减轻,炎细胞浸润减少;与对照组比较,模型组K17、IL-17A、IL-19及IL-23 mRNA水平、K17蛋白表达明显升高,Rsv治疗后K17、IL-17A、IL-19 mRNA水平、K17蛋白表达显著降低。结论 白藜芦醇通过抑制K17及炎症分子表达,改善IMQ诱导的银屑病样皮肤损伤。     

小分子阿胶对小鼠免疫功能的影响

目的 研究小分子阿胶对小鼠免疫功能的调节作用。方法 将ICR小鼠随机分为对照组、模型组、生血丸3.00 g/kg组和小分子阿胶3.00、1.50、0.75 g/kg组,ig给药14 d,ip环磷酰胺或氢化可的松建立免疫低下模型,用鸡红细胞诱导小鼠溶血素,测定小鼠血清溶血素水平,观察小分子阿胶对体液免疫的影响;采用二硝基氯苯诱导小鼠耳廓肿胀,检测小鼠耳廓肿胀度,观察小分子阿胶对细胞免疫的影响;利用流式细胞术对小鼠淋巴细胞亚群进行分析,观察小分子阿胶对小鼠淋巴细胞分型的影响。结果 与模型组比较,小分子阿胶3.00、1.50、0.75 g/kg显著提高免疫功能低下小鼠血清溶血素含量（P<0.01）;3.00、1.50 g/kg显著提高小鼠耳廓肿胀度（P<0.01、0.05）;3.00 g/kg显著提高小鼠T淋巴细胞（CD3⁺）、辅助性T细胞和迟发超敏性T细胞（CD3⁺CD4⁺）占淋巴细胞的比例（P<0.01）。结论 小分子阿胶能提高小鼠体液免疫和细胞免疫功能,对免疫功能有正向调节作用。     

Rhododendron groenlandicum (Labrador tea), an antidiabetic plant from the traditional pharmacopoeia of the Canadian Eastern James Bay Cree,improves renal integrity in the diet-induced obese mouse model

Content Our team has identified Labrador tea [Rhododendron groenlandicum L. (Ericaceae)] as a potential antidiabetic plant from the traditional pharmacopoeia of the Eastern James Bay Cree. In a previous in vivo study, the plant extract was tested in a high-fat diet (HFD)-induced obese model using C57BL/6 mice and it improved glycaemia, insulinaemia and glucose tolerance.

Objective In the present study, we assessed the plant’s potential renoprotective effects.

Materials and methods Rhododendron groenlandicum was administered at 250?mg/kg/d to mice fed HFD for 8 weeks to induce obesity and mild diabetes. Histological (periodic acid–Schiff (PAS), Masson and Oil Red O staining), immunohistochemical (IHC) and biochemical parameters were assessed to evaluate the renoprotective potential of R. groenlandicum treatment for an additional 8 weeks.

Results Microalbuminuria and renal fibrosis were developed in HFD-fed mice. Meanwhile, there was a tendency for R. groenlandicum to improve microalbuminuria, with the values of albumin-creatinine ratio (ACR) reducing from 0.69 to 0.53. Renal fibrosis value was originally 4.85 arbitrary units (AU) in HFD-fed mice, dropped to 3.27 AU after receiving R. groenlandicum treatment. Rhododendron groenlandicum reduced renal steatosis by nearly one-half, whereas the expression of Bcl-2-modifying factor (BMF) diminished from 13.96 AU to 9.43 AU.

Discussion and conclusions Taken altogether, the results suggest that R. groenlandicum treatment can improve renal function impaired by HFD.     

Effect of aqueous extract of Achillea millefolium on the development of experimental autoimmune encephalomyelitis in C57BL/6 mice

Objective:

Achillea millefolium (A. millefolium) is widely used as an anti-inflammatory remedy in traditional and herbal medicine. In this study, we investigated the effect of an aqueous extract from A. millefolium on experimental autoimmune encephalomyelitis (EAE) and on the serum cytokine levels in C57BL/6 mice.

Materials and Methods:

EAE was induced in 63 C57BL/6 mice weighing 20-25 g (8 weeks old). Following immunization, the treatment protocol was initiated by using different doses of an aqueous extract from A. millefolium (1, 5, and 10 mg/mouse/day). Histopathologic assessments were performed by hematoxylin and eosin (H and E) and luxol fast blue (LFB) staining. Behavioral disabilities were recorded by a camera. Serum levels of interleukin (IL)-10, IL-12, and transforming growth factor (TGF)-β were measured using enzyme-linked immunosorbent assay (ELISA).

Results:

On average, mice developed classical behavioral disabilities of EAE, 13.2 ± 1.9 days following immunization. Treatment of mice with A. millefolium led to delay the appearance of behavioral disabilities along with reduced severity of the behavioral disabilities. Treatment with A. millefolium prevented weight loss and increased serum levels of TGF-β in immunized mice with MOG35-55. EAE-induced mice, which were treated with A. millefolium, had less cerebral infiltration of inflammatory cells.

Conclusion:

The results demonstrated that treatment with aqueous extract of A. millefolium may attenuate disease severity, inflammatory responses, and demyelinating lesions in EAE-induced mice. In addition, following treatment with A. millefolium, serum levels of TGF-βwere increased in EAE-induced mice.KEY WORDS: Achillea millefolium, cytokines, experimental autoimmune encephalomyelitis, multiple sclerosis