播娘蒿籽油对小鼠学习记忆能力的影响

目的探讨播娘蒿籽油对小鼠记忆获得障碍模型的影响。方法以跳台法和避暗法测试小鼠学习记忆的能力,用比色法测定小鼠脑组织胆碱乙酰转移酶(ChAT)、乙酰胆碱酯酶(AchE)活性,用碱性羟胺法测定乙酰胆碱(Ach)含量。结果播娘蒿籽油可减少小鼠跳台和避暗错误次数,并能增加小鼠脑组织乙酰胆碱(ACh)含量和胆碱乙酰转移酶(ChAT)活性,同时降低脑组织乙酰胆碱酯酶(AchE)活性,有助于小鼠空间学习记忆能力的改善。结论播娘蒿籽油可以显著促进小鼠记忆。     

Optimizing conventional DMARD therapy for Sjögren's syndrome

Primary Sjögren's syndrome (pSS) is an auto immune disorder characterized by exocrine dysfunction as a result of chronic inflammation of the glands. Part of the patients also develops inflammation in other organs. In a complex interplay of different cell types such as T-cells, B-cells, dendritic cells, monocytes/macrophages and NK cells and their effector molecules, all contribute to one of the ultimate hallmarks of pSS: B-cell hyperactivity, subsequent autoantibody production and eventually formation of germinal center-like structures in the salivary gland. Effective treatment options for this disease are currently lacking.Biological DMARDs (bDMARDs) including those targeting B-cells or B-cell activation (directly or indirectly) have been studied, so far with limited efficacy. Besides that, their high costs provide a major drawback for implementation. Relatively inexpensive conventional DMARDs (cDMARDs) with well-known safety profiles have been shown efficacious in numerous clinical studies in multiple (rheumatic) diseases. cDMARDs target several pathways that are crucial in pSS immunopathology and some have proven to effectively inhibit B-cell hyperactivity and immune activation when given to patients. However, strong conclusions about potential efficacy are hampered by lack of standardization of inclusion criteria and outcome measures, dosing and validated biomarkers for patient selection. Proper implementation of these could help to optimize the use of cDMARDs in pSS treatment. In analogy with effective treatment strategies in for example rheumatoid arthritis, combination of two cDMARDs targeting different dysregulated pathways might result in additive or synergistic inhibition of immune activation. In view of this and the unique and potent mechanisms of action to target immunopathology in pSS, optimizing cDMARDs for treatment of pSS is worthwhile.     

Acquired microvascular dysfunction in inflammatory bowel disease: Loss of nitric oxide-mediated vasodilation

BACKGROUND & AIMS: Inflammatory bowel disease (IBD; i.e., Crohn's disease, ulcerative colitis) is characterized by refractory inflammatory ulceration and damage to the intestine. Mechanisms underlying impaired healing are not defined. Because microvascular dysfunction resulting in diminished vasodilatory capacity and tissue hypoperfusion is associated with impaired wound healing, we hypothesized that microvascular dysfunction may also occur in chronic IBD. METHODS: Intact submucosal arterioles from control, involved, and uninvolved IBD specimens were assessed using in vitro videomicroscopy to assess endothelium-dependent vasodilation in response to acetylcholine (Ach) and fluorescence microscopy to detect oxyradicals. RESULTS: Normal microvessels dilated in a dose-dependent and endothelium-dependent manner to Ach (maximum, 82% +/- 2%; n = 34). Inhibition of nitric oxide synthase with N(G)-nitro-L-arginine methyl ester (L-NAME) reduced maximal dilation to 54% +/- 6% (P < 0.05, n = 7), and further reduction was observed after inhibiting cyclooxygenase (indomethacin; 23% +/- 10%, n = 6). Chronically inflamed IBD microvessels showed significantly reduced Ach-induced vasodilation (maximum, 15% +/- 2%; n = 33), with no effect of L-NAME. Indomethacin eliminated the remaining Ach-induced vasodilation, resulting in frank vasoconstriction (-54% +/- 9%, n = 6). Uninvolved IBD gut vessels and non-IBD inflammatory controls responded in a fashion similar to normal vessels. IBD-involved microvessels generated significantly higher levels of reactive oxygen species compared with control and uninvolved IBD vessels (P < 0.01). CONCLUSIONS: Human intestinal microvessels from chronically inflamed IBD show microvascular endothelial dysfunction, characterized by loss of NO-dependent dilation that may contribute to reduced perfusion, poor wound healing, and maintenance of chronic inflammation.     

水疗一号方对腹泻型肠易激综合征患者血清中乙酰胆碱和血管活性肠肽的影响

目的:观察水疗一号方治疗腹泻型肠易激综合征(diarrhea-dominant irritable bowel syndrome,IBS-D)临床疗效及其作用机制。方法:将40例IBS-D患者随机分成治疗组和对照组,每组20例。治疗组予水疗一号方结肠水疗,每次200 mL,1次/d;对照组予口服奥替溴铵片,每次40mg,3次/d。疗程均为2周。观察两组治疗前后临床症状积分,血清中Ach、VIP的水平变化以及临床疗效。结果:治疗组在治疗后临床症状积分改善、临床疗效方面优于对照组(均P<0.05);治疗组治疗后血清Ach、VIP水平降低,与对照组水平变化差异显著(均P<0.01)。结论:水疗一号方作用机理可能是通过调节Ach、VIP的分泌、抑制其异常升高,使胃肠道运动及分泌功能得以恢复而实现。     

脐血干细胞海马移植对VD大鼠脑内Ach及AchE活性的影响

目的观察海马移植脐血干细胞对血管性痴呆(VD)大鼠脑内Ach含量及AchE活性的影响。方法分离正常分娩胎儿的脐带血单个核细胞,以贴壁培养法得到间质干细胞(MSCs),采用RT-PCR方法检测Nestin及musashi-1。制作VD大鼠模型,8～10d后行脐血干细胞海马移植。移植4周后,检测大鼠的学习记忆能力,并检测其脑内乙酰胆碱(Ach)含量及乙酰胆碱脂酶(AchE)活性。结果脐血干细胞在分离后48h高表达Nestin及musashi-1;海马移植脐血干细胞4周后,治疗组与模型组比较,Ach含量及AchE活性明显升高(P<0.01),大鼠学习记忆能力增强。结论脐血中表达神经干细胞(NSCs)的标志物,海马移植脐血干细胞能明显改善VD大鼠胆碱能系统的功能,调节脑内Ach生理代谢,增强学习记忆能力,从而达到治疗VD的目的。     

复方大黄制剂对老龄小鼠大脑皮质和海马ChAT、AchE活性及Ach含量的影响

目的研究复方大黄制剂对老龄小鼠大脑皮质和海马ＣｈＡＴ、ＡｃｈＥ活性及Ａｃｈ含量的影响,以期从胆碱能神经药理学角度探讨其抗衰老作用机理。方法取１２月龄和３月龄小鼠,随机分组、设立对照。ＣｈＡＴ、ＡｃｈＥ活性测定分别采用Ｆｏｎｎｕｎ氏法和ＲＲＡ法,Ａｃｈ含量测定采用荧光法。结果该药能显著提高１２月龄小鼠大脑皮质和海马中ＣｈＡＴ活性,并能显著降低ＡｃｈＥ活性,与空白对照组、非大黄气阴口服液组及安慰剂组比较均有非常显著性差异（Ｐ＜０．０１～０．００１）,但对Ａｃｈ含量无显著性影响,对３月龄小鼠也无上述作用。非大黄气阴口服液对１２月龄小鼠无上述影响。结论复方大黄制剂是通过影响老龄小鼠中枢胆碱能神经化学改善其衰老变化的。     

缺氧缺血新生鼠脑内乙酰胆碱水平的变化

目的 探讨缺氧缺血对新生鼠中枢胆碱能系统的远期影响及治疗措施。方法 采用碱性羟胺比色法对缺氧缺血新生鼠（7日龄）损伤后即刻及其14d后左、右脑乙酰胆碱（Ach）含量进行测定,并观察了损伤后即刻及3d后腹腔内连续7d注射4µg碱性成纤维生长因子（bFGF）对脑内Ach含量的影响。结果 缺氧缺血损伤后即刻,在脑Ach含量显著降低,（P﹤0.05）,于14d后仍未恢复;bFGF治疗对损伤后脑内Ach含量无显著影响。结论 缺氧缺血可损伤新生鼠中枢胆碱系统功能,此影响可持续至21日龄。bFGF对胆碱能损伤无明显保护作用。     

人参皂甙对实验性脑缺血脑组织内Ach,ChAT的影响

结扎蒙古沙土鼠左侧颈总动脉造成急性脑缺血后２ｈ，脑组织内Ａｃｈ及ＣｈＡＴ的活性明显降低，非缺血侧Ａｃｈ含量则无明显变化，于缺血前３Ｃｍｉｎ腹腔内注射人参皂甙２００ｍｇ／ｋｇ能明显提高缺血侧Ａｃｈ含量和ＣｈＡＴ活性，非缺血侧Ａｃｈ的含量也被提高。     

正交实验优选长松萝醇提工艺研究

目的 :以松萝酸得量为指标 ,研究优选长松萝的醇提工艺。方法 :采用正交实验法 ,考察回流时间、溶媒量、乙醇浓度和次数四因素对松萝酸得量的影响 ;双波长薄层扫描法测定松萝酸含量。结果 :乙醇浓度对松萝酸得量有非常显著性影响 (P<0 .0 1) ,提取次数对其有显著性影响 (P<0 .0 5 )。结论 :最佳工艺条件为 :95 %乙醇回流提取 2次 ,第 1次加 4倍溶媒提取 3h;第 2次加 3倍溶媒提取 2 h。