目的:研究曲札茋苷与盐酸法舒地尔注射液联用对小鼠缺血性脑损伤的保护作用.方法:采用小鼠双侧颈总动脉结扎模型,观察曲札茋苷联合盐酸法舒地尔对全脑缺血小鼠的耐缺氧时间的影响.采用线栓再灌注模型,观察联合用药对局灶性脑缺血再灌注小鼠的脑梗死体积、氧化应激、炎症因子的影响.结果:与模型组比较,曲札茋苷联合盐酸法舒地尔(3.35 mg/kg+7.5 mg/kg)尾静脉注射给药3次,均能延长全脑缺血模型小鼠的存活时间;单次静脉给药,均能降低缺血再灌注模型小鼠的神经行为学评分,降低脑梗死体积;提高血清中超氧化物歧化酶(SOD)活性,抑制血清中丙二醛(MDA)、肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(IL-1β)、白细胞介素-6(IL-6)的含量.结论:曲札茋苷联合盐酸法舒地尔注射液对小鼠缺血性脑损伤的保护作用优于两药单独应用,起到了协同增效的作用,其机制可能与减轻氧化应激和抑制炎症反应有关.

目的 探讨曲札茋苷注射液对二氯化钴诱导PC12细胞氧化应激的保护作用及其机制.方法 取对数生长期PC12细胞随机分为5组:对照组、模型组、曲札茋苷低水平组、曲札茋苷高水平组、依达拉奉组;甲基三氯硅烷(Methyltrichlorosilane,MTS)法检测细胞活力:分光光度法检测超氧化物歧化酶(Superox-ide dismutase,SOD)活性、乳酸脱氢酶(Lactate dehydrogenase,LDH)水平;荧光探针法检测活性氧(Reactive oxygen species,ROS)荧光强度;Western Blot法检测细胞中半胱氨酸天冬氨酸蛋白酶-3(Cysteinyl aspartate specific proteinase-3,Caspase-3)、B淋巴细胞瘤-2基因(B-cell lymphoma-2,Bcl-2)、Bcl-2-相关X(Bcl-2-Associ-ated X,Bax)蛋白的表达水平.结果 与对照组比较,模型组细胞活力下降,SOD活性降低,LD H释放增加,活性氧水平增高,Caspase-3,Bax蛋白的表达水平上升,Bcl-2蛋白表达水平下降(P<0.05);与模型组比较,曲札茋苷组、依达拉奉组细胞活力上升,SOD活性升高,LD H释放较少,活性氧水平降低,Caspase-3,Bax蛋白的表达水平下降,Bcl-2蛋白表达水平上升(P<0.05).结论 曲札茋苷可明显升高氧糖剥夺/复糖复氧PC12细胞的存活率,其机制可能是通过调控相关凋亡蛋白的表达,从而抑制细胞的凋亡.

目的 应用类过敏体内外评价体系,初步对注射用曲札芪苷进行安全性评价.方法 采用RBL-2H3细胞模型和小鼠体内模型(ICR及昆明种),以Compound48/80和清开灵注射液为阳性对照组,体外采用MTT法检测细胞活力,以组胺和β-氨基己糖苷酶的释放率为检测指标;体内通过尾静脉注射含伊文思蓝的受试物,检测小鼠耳廓蓝染发生率,伊文思蓝渗出量,血液中组胺、免疫球蛋白IgE(IgE)及细胞内皮生长因子含量.结果 RBL-2H3细胞体外检测显示,200μg·mL-1注射用曲札茋苷与阴性对照组比较,组胺和β-氨基己糖苷酶释放率差异无统计学意义;相当于临床剂量50倍(1.75 mg·mL-1)的注射用曲札茋苷未引起小鼠发生类过敏反应.结论 初步建立的类过敏反应体内外检测体系,适用于中药注射剂类过敏反应的快速筛查,注射用曲札芪苷在该体系中未见类过敏反应发生,初步说明具有较高的安全性.

目的:研究注射用曲札芪苷的镇咳、平喘、祛痰及对急性肺损伤治疗效果.方法:分别采用浓氨水致咳法、酚红排泌法、脂多糖致急性肺损伤、豚鼠磷酸组胺和氯化乙酰胆碱引喘法建立相应动物模型,通过观察并记录咳嗽次数、哮喘潜伏期,检测气管酚红排泌量,计算肺指数、肺含水量来探究曲札茋苷对实验动物的影响.结果:与模型组比较,注射用曲札芪苷5 mg/kg能明显减少浓氨水致小鼠咳嗽次数、降低脂多糖诱导小鼠急性肺损伤(Acute Lung Injury,ALI)后的肺指数和肺干湿重比,2.5 mg/kg、5 mg/kg能显著增加小鼠气管酚红排泌量,1.25 mg/kg能明显延长豚鼠哮喘潜伏期.结论:研究表明注射用曲札芪苷具有明显的镇咳、平喘、祛痰及治疗急性肺损伤作用,为其进一步的药用开发提供了实验依据.

p38MAPK通路是MAPK通路的重要组成部分,介导多种转录因子的表达,在细胞炎症、侵袭、凋亡中发挥着重要作用.脑缺血再灌注损伤是缺血的脑组织在恢复供血的情况下,损伤程度加重的病理现象.近些年研究发现p38MAPK通路与脑缺血再灌注损伤息息相关.本文就近年来对p38MAPK通路与脑缺血再灌注损伤的机制研究进展进行综述.

目的:考察注射用曲札芪苷对小鼠实验性脑水肿的影响,为临床应用提供实验依据.方法:采用小鼠局灶永久性脑缺血模型、全脑缺血再灌注模型、脂多糖致感染模型,以干湿质量法测定脑含水量.结果:注射用曲札芪苷以16,8和4 mg·kg-1剂量单次静脉注射给药,中高剂量可明显降低大脑中动脉梗死25 h后小鼠的脑含水量;以20,10和5 mg·kg-1剂量连续腹腔注射3d,能明显降低双侧颈总动脉缺血/再灌注小鼠的脑含水量,明显降低脂多糖感染小鼠的脑含水量.结论:注射用曲札芪苷能明显降低3种模型小鼠的脑含水量,提示注射用曲札芪苷对急性缺血性脑卒中继发的脑水肿及感染性脑水肿均具有潜在的治疗作用.

Aim To establish a novel acute hyperuricemia mouse model and apply it to evaluate the hyporucicemia effects of Ulodesine, a purine nucleoside phosphorylase(PNP) inhibitor.Methods The mice were intraperitoneal injected inosine and subcutaneous injected Oteracil potassium to induce accumulation of uric acid, and the animal blood was collected from eyeball or vena angularis in different time points.The levels of serum uric acid were measured and determined to test whether the acute hyperuricemia mouse model were successful or not.In order to verify the hyperuricemia seen in the model was associated with the accumulation of inosine, which was converted to uric acid by action of PNP,hyporucicemia effects of Ulodesine, a PNP inhibitor, was assessed in an enzyme assay and confirmed by using the newly established model.Result Accumulation of uric acid in the blood of mouse models was observed by combined injections of intraperitoneal 200 mg·kg-1 inosine and subcutaneous 200 mg·kg-1 Oteracil potassium respectively after 1.5 h.The enzyme assay indicated that Ulodesine was a potently PNP inhibitor with IC50 of 2.293 nmol·L-1.IV injection of Ulodesine eliminated uric acid accumulations in blood of the mouse model, which was expected as the in vivo action of Ulodesine.Conclusions A novel acute hyperuricemia mouse model is established.This is a relatively easy and more effective protocol to generate the hyperuricemia in mice, which will be a useful platform to assess the anti-hyperuricemia activity of PNP-target drugs in vivo.

Norathyriol is a metabolite of mangiferin. Mangiferin has been reported to inhibit α-glucosidase. To the best of our knowledge, no study has been conducted to determine or compare those two compounds on inhibiting α-glucosidase in vitro and in vivo by far. In this study, we determined the inhibitory activity of norathyriol and mangiferin on α-glucosidase in vitro and evaluated their antidiabetic effect in diabetic mice. The results showed that norathyriol inhibited α-glucosidase in a noncompetitive manner with an IC50 value of 3.12 μM, which is more potent than mangiferin (IC50 = 358.54 μM) and positive drug acarbose (IC50 = 479.2 μM) in the zymological experiment. Both of norathyriol and mangiferin caused significant (p < 0.05) reduction in fasting blood glucose and the blood glucose levels at two hours after carbohydrate loading and it was interesting that mangiferin and norathyriol can make the decline of the blood glucose earlier than other groups ever including normal group in the starch tolerance test. However, norathyriol and mangiferin did not significantly influence carbohydrate absorption in the glucose tolerance test. Therefore, the antidiabetic effects of norathyriol and mangiferin might be associated with α-glucosidase, and norathyriol was more potent than mangiferin.

目的研究银芩胶囊的抗炎作用,为临床用药提供依据。方法采用二甲苯诱导的小鼠耳肿胀、角叉菜胶诱导的大鼠足爪肿胀模型,观察银芩胶囊的抗炎作用。结果银芩胶囊对模型动物均呈一定的炎症抑制作用(P<0.05或P<0.01),且其与人临床等效剂量组的抗炎效果优于双黄连胶囊对照组。结论银芩胶囊具有良好的抗炎作用。