镇肝熄风汤对帕金森病模型小鼠神经行为学及黑质14-3-3、酪氢酸羟化酶表达的影响

目的: 观察镇肝熄风汤对1-甲基-4-苯基-1,2,3,6-四氢吡啶(1-methy-4-phenyl-1,2,3,6-tetrahy-dropyridine MPTP)诱导的C57BL/6小鼠帕金森病模型自主活动的影响及其可能机制。 方法: 连续灌胃14 d给予不同剂量的镇肝熄风汤(12.5, 25,50 g·kg^-1)和司来吉兰(10 mg·kg^-1)预处理,于给药第11天开始连续4 d C57BL/6小鼠皮下注射MPTP(30 mg·kg^-1)制备帕金森病小鼠模型。通过自主活动实验 观察动物行为学表现,采用实时定量RT-PCR法检测多功能蛋白14-3-3和酪氨酸羟化酶(tyrosine hydroxylase, TH) mRNA表达,Western blot方法检测多功能蛋白14-3-3,TH蛋白表达。 结果: 与模型组比较,镇肝熄风汤可显著增强帕金森病小鼠自主活动能力(均P<0.05),上调多功能蛋白14-3-3和TH mRNA和蛋白表达(均P<0.05)。 结论: 镇肝熄风汤具有抗实验性帕金森病的作用,其机制可能与上调多功能蛋白14-3-3和TH的mRNA和蛋白表达有关。     

人参提取物对C57小鼠生发作用的影响

目的: 研究人参提取物对C57BL/6J小鼠毛发生长促进作用及其机制。 方法: 实验分为阳性对照组(章光101)、空白对照组、人参提取物高、中、低(2, 1, 0.5 g·mL^-1)剂量组。小鼠脱毛,通过观察脱毛区肤色的变化和组织学检查,研究人参提取物对小鼠毛发生长周期的影响;采用红外测温仪观察对小鼠皮肤温度的影响;采用浊度法和底物发色法,观察其抗血小板聚集的作用,初步探讨其促进毛发生长的机制。 结果: 人参各剂量组均能诱导C57BL/6J小鼠毛发生长,使其从休止期进入生长期,但对毛发的最终长度无影响,且呈现一定的剂量依赖作用(P<0.01),高剂量组与阳性组无显著性差异;组织学检查显示人参提取物可以刺激毛囊生长,产生黑色素;给药20,60 min后,人参各剂量组均能显著提高小鼠的体温(P<0.01),120 min后,恢复到给药前水平;人参高、中、低剂量组对血小板活化因子(PAF)诱导的大鼠5 min时血小板聚集率分别为49.41%,27.80%,18.39%(均P<0.01),且呈现一定的剂量依赖作用,与阳性对照组则无显著性差异;其抗血小板聚集的作用与抗凝血酶有关, 人参高、中、低剂量组的凝血酶抑制率分别为(20.24±2.72)%,(15.42±1.03)%,(8.61±0.80)%(P<0.01)。 结论: 人参提取物具有明显的促进毛发生长的作用,其机制与扩张皮肤毛细血管、改善局部微循环有关。     

Antiproliferative effects of magnosalin derived from ‘Shin'i’ (Flos Magnoliae), a Japanese Sino-medicine,on cultured synovial cells of MRL/1 and C57BL/6J mice

The in vitro inhibitory effect of magnosalin, a compound derived from ‘Shin'i’ (Flos Magnoliae), on the proliferation of synovial cells from rheumatoid MRL/1 mice and normal C57BL/6J mice (control) was evaluated. DNA synthesis in synovial cells was induced with 5% fetal bovine serum (FBS) or interleukin-1α (IL-1α, 1 U/mL), and measured with a [³H]-thymidine incorporation assay. Basic fibroblast growth factor (bFGF) and platelet-derived growth factor (PDGF) were used in some experiments. FBS (5%)-stimulated proliferation (cell number) was significantly greater in MRL/1 mouse synovial cells than in C57BL/6J synovial cells. Magnosalin (23.9 μM ) inhibited [³H]-thymidine incorporation into both MRL/1 and C57BL/6J mouse synovial cells, whereas magnoshinin (23.4 μM ) inhibited [³H]-thymidine incorporation only into normal C57BL/6J synovial cells. Corticosterone, bucillamine, and tetrandrine, positive controls, also inhibited [³H]-thymidine incorporation into synovial cells. Reticuline (100 μM ) and coclaurine (100 μM ), structural moieties of tetrandrine, had no significant effects except for an inhibitory effect of coclaurine on normal C57BL/6J cells. Butylidenephthalide (100 μM ), a compound derived from Cnidium Rhizome, did not inhibit [³H]-thymidine incorporation into synovial cells of MRL/1 or normal mice. IL-1α, bFGF, and PDGF each stimulated [³H]-thymidine incorporation into synovial cells of normal mice in a concentration-dependent manner in the presence of 1% FBS. Of these cytokines, IL-1α was the most effective at the lowest concentration (0.57 pM ; 1 U/mL); it was as effective as 5% FBS. Both magnosalin (2.39 μM ) and tetrandrine (0.1 μM ) inhibited IL-1α (1 U/mL)-induced [³H]-thymidine incorporation into normal C57BL/6J synovial cells. Magnosalin appears to be an important lead compound for the development of a new class of antirheumatic agents.     

4种小鼠的寒、热体质研究

目的研究4种品系小鼠的寒、热体质。方法8～9周龄昆明、BALB/c、C57BL/6J、ICR小鼠,以及4～5周龄昆明小鼠,同步系统检测其生物学特性,然后以统一的评价标准评价4种品系小鼠的寒、热体质。并对BALB/c小鼠给予参桂理中丸和利血平做药物反证。结果①4～5周龄昆明小鼠与8～9周龄昆明小鼠比较体质明显偏热;②BALB/c小鼠与C57BL/6J小鼠比较体质偏寒;③8～9周龄雄性BALB/c小鼠、雄性和雌性C57BL/6J小鼠与8～9周龄相应性别昆明小鼠比较体质无明显差异;8～9周龄雌性BALB/c小鼠与8～9周龄雌性昆明小鼠比较体质偏寒;④8～9周龄ICR小鼠与8～9周龄BALB/c小鼠、C57BL/6J小鼠比较体质偏热;8～9周龄雄性ICR小鼠与8～9周龄雄性昆明小鼠比较体质偏热。结论4种品系小鼠存在寒、热体质差异。     

铁皮石斛多糖促进毛发生长的实验研究

目的：观察铁皮石斛多糖（DCP）促毛发生长的功效并探讨其作用机制,为铁皮石斛的开发利用奠定基础。方法：采用水提醇沉法提取DCP,并用苯酚-硫酸法测定其多糖含量。取C57BL/6J小鼠30只,用脱毛膏去除其背部毛发建立脱发模型,分为对照组、阳性对照组和DCP组,每日分别涂抹超纯水、米诺地尔酊、DCP（5.0 g·L^-1）l 次,每次 0.2 mL,连续给药21 d,应用小鼠毛发生长情况评分标准对C57BL/6J小鼠给药7,14 d毛发生长情况进行评分,及称量给药21 d C57BL/6J小鼠单位脱毛区域毛发质量评价DCP对C57BL/6J小鼠毛发生长的影响。采用MTT法和RT-PCR法分别评价DCP对人永生化角质形成细胞（HaCaT细胞）增殖和对HaCaT细胞血管内皮生长因子（VEGF）mRNA表达的影响。结果：DCP提取率为29.87%,DCP质量分数为79.65%。DCP组C57BL/6J小鼠的毛发生长平均得分、平均质量均显著优于对照组;DCP组HaCaT细胞生存率和VEGF mRNA的表达水平与对照组比较均显著提高。结论：DCP具有促毛发生长的作用,其机制可能是上调VEGF mRNA的表达。     

青钱柳对糖尿病小鼠肝脏糖脂代谢影响及机制研究＊

目的 观察青钱柳水提物（Cyclocarya paliurus aqueous extract， CPAE）对自发性2型糖尿病小鼠（db/db小鼠）肝脏糖脂代谢影响，并探讨其作用机制。方法 取4周龄雄性C57BL/6J小鼠为正常对照组，将同周龄成模雄性db/db小鼠根据血糖、体质量随机分为模型组、盐酸二甲双胍组（0.13 g·kg^-1·d^-1）及青钱柳水提物组（2 g·kg^-1·d^-1），每组10只。干预6周，每2周检测小鼠体质量、空腹血糖（FBG），6周后检测空腹血糖（Fasting blood glucose， FBG）、甘油三脂（Triglyceride， TG）、总胆固醇（Total cholesterol， TC）、游离脂肪酸（Free fatty acid， FFA）、空腹血清胰岛素（Fasting serum insulin， FINS），同时计算胰岛素抵抗指数（Homeostasis model assessment insulin resistance， HOMA-IR）；苏木精-伊红染色（Hematoxylin-eosin stain， HE stain）观察肝脏脂质蓄积情况；过碘酸-Schiff染色法（Periodic Acid-Schiff stain， PAS stain）观察肝组织肝糖原含量；采用Western Blot法检测肝脏P-AMPK、PGC-1α蛋白表达水平。结果 与模型组相比，CPAE可降低db/db小鼠FBG、TC、FFA、FINS及胰岛素抵抗指数（P < 0.01），抑制脂质在肝脏沉积，增加肝糖原含量（P < 0.05），提高肝脏P-AMPK蛋白表达水平（P < 0.01），抑制PGC-1α蛋白表达水平（P < 0.01）。结论 CPAE可降低db/db小鼠FBG、TC、FFA、FINS及胰岛素抵抗指数，改善胰岛素抵抗，增加肝糖原含量，抑制糖异生，其作用机制可能与调节肝脏AMPK/PGC-1α信号通路相关。     

The mechanism of sesame oil in ameliorating experimental autoimmune encephalomyelitis in C57BL/6 mice

Experimental autoimmune encephalomyelitis (EAE) is a Th1 cell‐mediated autoimmune disease of the CNS that serves as an animal model for multiple sclerosis (MS). The study investigated the effectiveness of treatment with sesame oil on the development of EAE. EAE was induced in 8 week old C57BL/6 mice with an emulsion of MOG35‐55. Therapy with sesame oil (4 mL/kg/day as oral gavage) was started on day 3 before the immunization. IFN‐gamma and IL‐10 production from cultured spleen supernatants were determined by the ELISA method. The results showed that daily oral gavage of sesame oil significantly reduced the clinical symptoms of EAE in C57BL/6 mice. In addition, sesame oil‐treated mice displayed a significantly delayed disease onset. Mononuclear cells isolated from spleen of sesame oil‐treated mice showed a significant decrease in the production of IFN‐gamma compared with control mice (p = 0.001). IL‐10 production was also enhanced in splenic mononuclear cells in sesame oil‐treated mice. The ratio of IFN‐gamma to IL‐10 in sesame oil‐treated EAE mice was significantly less than in non‐treated EAE mice (p = 0.01). This report indicates that sesame oil therapy protected mice from developing EAE by reducing IFN‐gamma secretion. Thus, sesame oil treatment may be effective in MS patients by immunomodulating the Th1 immune response. Copyright © 2011 John Wiley & Sons, Ltd.     

Effect of ninjin-youei-to on Th1/Th2 type cytokine production in different mouse strains

Ninjin-youei-to (NYT; ren-shen-yang-rong-tang in Chinese) is a traditional herbal formula, which is widely used in Japan, Korea and China to modulate physiological immunity. The effects of oral administration of NYT on cytokine production from splenocytes were investigated in both C57BL/6 and BALB/c mice in which Th1 and Th2 were dominant, respectively. Splenocytes from C57BL/6 and BALB/c mice, which took NYT orally forfour weeks, were cultured with anti-mouse CD3 mAb, and the supernatant was examined for cytokine production using enzyme-linked immunosorbent assay (ELISA). Administration of NYT to C57BL/6 mice, increased the production of interleukin-4 (IL-4) significantly, and slightly decreased interferon-y (IFN-gamma) production from splenocytes. In contrast, the same treatment significantly increased IFN-gamma secretion from splenocytes of BALB/c mice. No remarkable changes of IL-12 production from splenocytes were observed in either strain of mice. These results suggest that oral administration of NYT ameliorates the excessive inclination of Th1 and Th2 type cytokine production, and NYT may provide a beneficial effects for the treatment of diseases caused by a skewed Th1-Th2 balance in the immune system.     

Effects of olive leaf extract and its main component oleuroepin on acute ultraviolet B irradiation‐induced skin changes in C57BL/6J mice

Olive (Olea europaea L.) leaves have long been used in folk medicine and herbal tea in Europe and the Mediterranean area. The Mediterranean climate is characterized by high temperatures, and by strong ultraviolet B (UVB) radiation causing the skin to age, increasing wrinkling, pigmentation and skin thickness. The aim of this study was to examine the effects of an olive leaf extract and its component oleuropein on skin damage caused by acute UVB irradiation in C57BL/6J mice. The extract (300 or 1000 mg/kg) and oleuropein (25 or 85 mg/kg) were administered orally twice daily for 14 days. UVB was administered daily at a dose of 120 mJ/cm² for the first 5 days and then every other day for 9 days. Both treatments inhibited the increases in skin thickness induced by radiation. They also inhibited increases in the Ki‐67‐ and 8‐hydroxy‐2′‐deoxyguanosine‐positive cell numbers, melanin granule area and matrix metalloproteinase‐13 (MMP‐13) expression. These preventive effects on UVB‐induced skin damage might be caused in part by inhibiting the degradation of extracellular matrixes in the corium, and by the proliferation of epidermal cells through the inhibition of increases in MMP‐13 levels and reactive oxygen species induced by irradiation. Copyright © 2009 John Wiley & Sons, Ltd.     

Antilipogenic effect of green tea extract in C57BL/6J‐Lepob/ob mice

The objective of this study was to determine the effects of green tea extract (GTE) on lipid metabolism in obese animal models. Male C57BL/6J‐Lepob/ob mice were divided into control and GTE (0.05 g/100 g diet) groups, which were fed a high‐fat (20 g/100 g diet) diet for 12 weeks. Supplementation of GTE significantly reduced (p < 0.01) perirenal and total white adipose tissue weights compared with the control group. Also, the plasma HDL‐cholesterol level was significantly higher in the GTE group than in the control group, therefore the GTE group showed a higher HDL‐cholesterol/total‐cholesterol ratio (HTR) and lower atherogenic index (AI) level than the control group. A reduction of hepatic triglyceride content and adipose tissue weight in the GTE group was related to the suppression of enzyme activities for fatty acid synthesis (glucose‐6‐phosphate dehydrogenase and malic enzyme) without affecting fatty acid oxidation enzyme (β‐oxidation and carnitine palmitoyl transferase) activities in hepatic and adipose tissue. The current results showed that supplementation of green tea extract is beneficial for antiobesity by the suppression of lipogenesis via regulation of related enzyme activities in hepatic and adipose tissue. Copyright © 2008 John Wiley & Sons, Ltd.     

通心络抑制KK/Upj-Ay小鼠视网膜组织HIF-1a/VEGF/VEGFR-2表达

目的:观察通心络对自发糖尿病KK/Upj-Ay小鼠视网膜组织缺氧诱导因子-1a(HIF-1a),血管内皮生长因子(VEGF)和血管内皮生长因子受体2(VEGFR2)基因及蛋白表达的影响,探讨通心络对糖尿病视网膜病变的保护机制。方法:40只KK/Upj-Ay小鼠随机分为模型组和通心络低、中、高剂量组(通心络生药1,2,4 g·kg-1,ig给药12周),实验以C57BL/6小鼠为正常组。用血液黏度仪测定全血黏度和血浆黏度、红细胞变形聚集仪测定红细胞聚集指数;应用实时荧光定量PCR法检测各组小鼠视网膜组织中VEGF和VEGFR2的基因表达;Western blot法检测视网膜组织中HIF-1a,VEGF,VEGFR2蛋白的表达。结果:与正常组C57BL/6小鼠比较,模型组小鼠全血黏度、血浆黏度、红细胞聚集指数明显升高(P0.01);与模型组比较,应用通心络中、高剂量治疗的KK/Upj-Ay小鼠红细胞聚集指数明显降低(P0.05,P0.01);高剂量通心络组的低切全血黏度降低(P0.05),血浆黏度较模型组也显著降低(P0.01)。模型组小鼠视网膜组织HIF-1a,VEGF,VEGFR2蛋白和VEGF,VEGFR2 mRNA表达较正常组明显增高(P0.01);通心络ig治疗后,各剂量组HIF-1a,VEGF,VEGFR2 mRNA和蛋白表达水平均较模型组明显下降(P0.01)。结论:通心络可抑制自发性糖尿病小鼠视网膜组织HIF-1a/VEGF/VEGFR-2信号途径,此作用可能与其改善糖尿病血液流变学相关。     

The effects of hypoglycemia and weight loss of total lignans from Fructus Arctii in KKAy mice and its mechanisms of the activity

Fructus Arctii (great burdock achene) is the dried ripe fruit of Arctium lappa L. (family Asteraceae) and is included in the Chinese pharmacopoeia. It has been reported that the clinical use of Fructus Arctii resulted in a satisfactory hypoglycemic effect in diabetic patients. This study aimed to investigate antidiabetic activity and mechanism of total lignans from Fructus Arctii (TLFA) in KKAy mice, a spontaneous Type 2 diabetic rodent model that exhibits marked obesity. In this study, KKAy mice were gavaged once daily with solvents (0.5% sodium carboxymethyl cellulose), TLFA (250 and 125 mg/kg), or metformin (200 mg/kg) for 11 weeks, and C57BL/6J mice treated with saline solution (0.9%, w/v) were used as normal control. The results indicate that TLFA has dual effects of hypoglycemia and weight loss, and administration of TLFA in KKAy mice could decrease fasting blood glucose, glycated hemoglobin, and body weight; improve oral glucose tolerance; increase high density lipoprotein cholesterol; and decrease triglycerides and free fatty acid in mice serum. Its efficacy may associate with multiple mechanisms of action such as stimulation of insulin secretion, activation of phosphatidylinositol 3‐kinase/protein kinase B, and adenosine‐monophosphate‐activated protein kinase signaling pathway, decreasing leptin.     

Effects of grape seed extract and its ethylacetate/ethanol fraction on blood glucose levels in a model of type 2 diabetes

The present study observed the effects of grape seed extract (GSE) and its ethylacetate (E) and ethylacetate/ethanol (EE) fractions on blood glucose levels in C57BL/KsJ‐lepr^db/lepr^db (db/db) mice at 4–12 weeks of age. In the GSE‐ and EE fraction‐treated db/db group, the blood glucose concentration began to be lower than that in the vehicle‐treated db/db group at 6 weeks after treatment, while the blood glucose concentration in the E fraction‐treated db/db group was similar to that in the vehicle‐treated db/db group. The glycosylated hemoglobin (HbA1c) level in the vehicle‐treated db/db groups was 9.3%, whereas HbA1c levels in the GSE‐ and EE fraction‐treated db/db group decreased significantly to 5.7% and 6.1%, respectively, at 8 weeks after treatment. However, administration of GSE and its EE fraction did not show any significant effects on body weights and food consumption in db/db mice. These results suggest that GSE and its EE fraction have a potential to decrease the blood glucose and HbA1c level, which is applicable to good healthy foods for reducing blood glucose levels. Copyright © 2009 John Wiley & Sons, Ltd.     

三氧化二砷对MRL/lpr小鼠CD4+T细胞增殖和IFN-γ、IL-4分泌的调节作用

 目的探讨三氧化二砷(ATO)对MRL/lpr狼疮小鼠脾脏CD4^+T细胞增殖以及IFN-γ和IL-4转录和翻译水平的影响。方法免疫磁珠分别分选15只MRL/lpr狼疮小鼠和15只C57BL正常对照小鼠脾脏CD4⁺T细胞,进而将CD4⁺T细胞随机分为空白组(RPMI1640),对照组(PHA20mg·L^-1+IL-21000u·mL^-1),ATO组[PHA20mg·L^-1+IL-21000u·mL^-1(48h)后+ATO1.0μmol·L^-1],体外共培养至72h。采用细胞计数试剂盒(CCK-8)检测3组CD4⁺T细胞的增殖和抑制水平;酶联免疫吸附反应(ELISA)检测上清液中IFN-γ和IL-4水平;逆转录-聚合酶链反应(RT-PCR)检测上述细胞因子基因的转录水平。结果①分选后获得的CD4⁺T细胞纯度为(94.12±1.08)%,细胞存活率为(95.82±3.41)%;②MRL/lpr小鼠对照组CD4⁺T细胞的增殖水平(A值)(0.343±0.019)较空白组(0.054±0.008)高(P<0.001);却低于C57BL小鼠对照组的水平(0.375±0.018)(P<0.05);③MRL/lpr和C57BL小鼠ATO组CD4⁺T细胞增殖水平(A值)分别为(0.324±0.013)和(0.362±0.013),均低于对照组(P<0.05,P<0.05);④MRL/lpr小鼠对照组IFN-γ的表达水平[(562.287±60.345)ng·L^-1]明显高于C57BL小鼠对照组[(253.208±59.434)ng·L^-1](P<0.05);ATO对MRL/lpr小鼠IFN-γ的抑制程度大于C57BL小鼠(P<0.05);MRL/lpr小鼠对照组的IL-4表达水平[(41.332±8.039)ng·L^-1]与ATO组[(23.046±3.253)ng·L^-1]和C57BL小鼠对照组[(29.303±8.038)ng·L^-1]比较,也具有明显的统计学差异(P<0.05和P<0.05);ATO对MRL/lpr小鼠IL-4的抑制程度高于C57BL小鼠(P<0.05);⑤在转录水平上,与C57BL小鼠相比,ATO对MRL/lpr小鼠IFN-γmRNA和IL-4mRNA的抑制程度更加明显(P<0.05和P<0.05);ATO对IFN-γ和IL-4表达水平的抑制和转录水平的抑制正相关,r=0.720(P<0.001)和r=0.557(P<0.01)。结论MRL/lpr小鼠存在CD4⁺T细胞的异常增殖,ATO能在不影响细胞存活率的浓度下抑制MRL/lpr小鼠CD4⁺T细胞的异常增殖活化,通过抑制其细胞因子IFN-γ和IL-4的mRNA分泌影响两者的表达,且对MRL/lpr小鼠抑制程度大于C57BL小鼠,表明ATO能抑制狼疮鼠的异常免疫功能,可进一步用于SLE的治疗。     

Hair Growth Activity of Crataegus pinnatifida on C57BL/6 Mouse Model

Crataegus pinnatifida has a long history of use in traditional oriental herbal medicine to stimulating digestion and improving blood circulation. Based on nutrition of hair, the present study was conducted to assess the effect of C. pinnatifida extract on hair growth using mouse model and its mechanisms of action. The C. pinnatifida extract containing the contents of total polyphenol of 5.88□0.82 g gallic acid/100 g extract and proanthocyanidin of 9.15□1.58 mg cyaniding chloride/100 g extract was orally administered daily at a dosage of 50 mg/kg weight to the 7‐week‐old C57BL/6 mice in telogen. The C. pinnatifida extract promoted hair growth by inducing anagen phase in mice in telogen, reflected by color of skin, thickness of hair shaft, and density of hair. The ratio of anagento telogen was determined by shape of hair follicles in vertically sectioned slide and increased by oral administration of C. pinnatifida extract. The number and the size of hair follicles were also enlarged, indicating anagen phase induction. The proliferation of human dermal papilla cells (hDPC) was accelerated by addition of C. pinnatifida extract, which activated the signaling of mitogen‐activated protein kinases (Erk, p‐38, and JNK) and Akt. Moreover, the ratio of Bcl‐2/Bax as the determinant of cell fate was also raised in skin. These results suggest that the C. pinnatifida extract promotes hair growth by inducing anagen phase, which might be mediated by the activation of cellular signalings that enhance the survival of cultured hDPC and the increase of the ratio of Bcl‐2 to Bax that protects cells against cell death. Copyright © 2012 John Wiley & Sons, Ltd.     

补阳还五汤加味预防动脉粥样硬化形成机制

目的:探究补阳还五汤加味对动脉粥样硬化(AS)形成的预防及机制研究。方法:将30只雄性载脂蛋白E基因敲除小鼠(Apo E-/-小鼠)随机分为Apo E-/-小鼠组、模型组、补阳还五汤加味组和辛伐他汀组,另以正常雄性C57BL/6J小鼠设组。模型组、补阳还五汤加味组和辛伐他汀组采用高脂饮食造模。第4周后,补阳还五汤加味组和辛伐他汀组分别灌以补阳还五汤20 g·kg~(-1)+水蛭粉0.46 g·kg~(-1),辛伐他汀3 mg·kg~(-1)。第9周后,检测血清总胆固醇(TC),甘油三酯(TG),高密度脂蛋白胆固醇(HDL-C)和低密度脂蛋白胆固醇(LDL-C)值,取动物主动脉根部经苏木素-伊红(HE)常规染色后观察组织形态变化并测量纤维帽厚度和内-中膜厚度、检测主动脉p38丝裂原活化蛋白激酶(p38MAPK)和细胞外信号调节激酶5(ERK5)蛋白表达变化。结果:血脂水平,与C57BL/6J小鼠正常组比较,Apo E-/-小鼠组和模型组TC,TG,LDL-C均升高且HDL-C均降低(P0.01);与模型组比较,补阳还五汤加味组与辛伐他汀组均能降低Apo E-/-小鼠TC,TG,LDL-C水平,同时升高HDL-C(P0.05,P0.01)。HE染色,C57BL/6J小鼠正常组主动脉管壁无斑块形成,Apo E-/-小鼠组管壁有极少斑块形成,内-中膜略有增厚。模型组斑块形成明显,内-中膜明显增厚。补阳还五汤加味组与辛伐他汀组较模型组斑块减少,内-中膜厚度减少。蛋白表达,与C57BL/6J小鼠正常组比较,模型组主动脉组织中p38MAPK的蛋白表达量增多(P0.01),ERK5的蛋白表达量减少(P0.01);与模型组比较,补阳还五汤加味组和辛伐他汀组均能降低p38MAPK蛋白的表达量(P0.01),增加组织中ERK5蛋白的表达(P0.01)。结论:补阳还五汤加味与辛伐他汀均有预防AS的作用。补阳还五汤加味预防AS发生的机制可能与干预MAPK信号通路中的p38MAPK,ERK5途径有关。     

Nimbolide Inhibits Nuclear Factor‐КB Pathway in Intestinal Epithelial Cells and Macrophages and Alleviates Experimental Colitis in Mice

Nimbolide is a limonoid extracted from neem tree (Azadirachta indica) that has antiinflammatory properties. The effect of nimbolide on the nuclear factor‐kappa B (NF‐κB) pathway in intestinal epithelial cells (IECs), macrophages and in murine colitis models was investigated. The IEC COLO 205, the murine macrophage cell line RAW 264.7, and peritoneal macrophages from interleukin‐10‐deficient (IL‐10^?/?) mice were preconditioned with nimbolide and then stimulated with tumor necrosis factor‐α (TNF‐α) or lipopolysaccharide. Dextran sulfate sodium‐induced acute colitis model and chronic colitis model in IL‐10^?/? mice were used for in vivo experiments. Nimbolide significantly suppressed the expression of inflammatory cytokines (IL‐6, IL‐8, IL‐12, and TNF‐α) and inhibited the phosphorylation of IκBα and the DNA‐binding affinity of NF‐κB in IECs and macrophages. Nimbolide ameliorated weight loss, colon shortening, disease activity index score, and histologic scores in dextran sulfate sodium colitis. It also improved histopathologic scores in the chronic colitis of IL‐10^?/? mice. Staining for phosphorylated IκBα was significantly decreased in the colon tissue after treatment with nimbolide in both models. Nimbolide inhibits NF‐κB signaling in IECs and macrophages and ameliorates experimental colitis in mice. These results suggest nimbolide could be a potentially new treatment for inflammatory bowel disease. Copyright © 2016 John Wiley & Sons, Ltd.     

The functional assessment of Alpinia pricei on metabolic syndrome induced by sucrose‐containing drinking water in mice

This study was designed to test whether Alpinia pricei (AP), a member of the ginger family indigenous to Taiwan, reduced metabolic syndrome induced by sucrose‐containing drinking water in C57BL/6J mice. Mice given a chow diet were divided into a control group (C) or a test group given 30% sucrose water (SW) to drink ad libitum. After 22 weeks, mice in the SW group were subdivided into SW and SW + AP groups, the latter receiving a chow diet with an ethanol extract of AP (1500 mg/kg dosage). Four weeks later, bio‐indexes associated with metabolic syndrome were measured. Compared with the C group, the SW group had significantly higher body weight, visceral fat weights, serum and tissue lipid, serum insulin level and the area under the curve for blood glucose of the insulin tolerance test (p < 0.05). These indicators in the SW + AP group were lower than in the SW group except for serum lipid, although slightly higher than the C group. The SW + AP group also showed significantly lower serum levels of leptin and tumor necrosis factor‐α and a significantly higher level of adiponectin than the SW group. These results indicated that visceral adiposity and insulin resistance induced by sucrose water drinking might be alleviated by AP supplementation. Copyright © 2008 John Wiley & Sons, Ltd.     

四神丸和葛根芩连片对DSS诱导的小鼠实验性结肠炎的作用比较

目的: 比较四神丸和葛根芩连片对硫酸葡聚糖钠(DSS)诱导的小鼠急性和慢性结肠炎的治疗作用。 方法: 急性或慢性结肠炎实验中C57BL/6J小鼠均随机分为4组,即正常组,DSS急性或慢性模型组,四神丸组(2.25 g ·kg^-1),葛根芩连片组(6.5 g ·kg^-1)。4%DSS连续给小鼠自由饮用5 d制备急性结肠炎模型;3%DSS给小鼠4次循环饮用(1~5 d,8~12 d,15~19 d,22~26 d)制备慢性结肠炎模型。急性模型于DSS饮水次日开始给药,连续ig给药8 d;慢性模型于DSS饮水2次循环后开始给药,连续给药16 d。分别测定小鼠疾病活动度指数(DAI)和结肠组织中髓过氧化物酶(MPO)活性,HE染色观察结肠组织学变化。 结果: 与正常组比较,模型组急性结肠炎与慢性结肠炎小鼠DAI均明显升高,结肠组织炎症损伤较为明显,MPO活性明显升高(P<0.05,P<0.01);急性结肠炎中葛根芩连片从第5天开始、四神丸从第7天开始显著改善小鼠DAI(P<0.05),二者均能显著减轻小鼠结肠组织炎症损伤(P<0.01,P<0.05),并降低结肠组织中MPO活性(P<0.05,P<0.01);慢性结肠炎中四神丸从第18至22天及24天可显著改善模型小鼠的DAI(P<0.05),并能减轻结肠组织炎症损伤(P<0.05),葛根芩连片对慢性结肠炎小鼠各指标均无显著性改善。 结论: 四神丸对DSS诱导的急性及慢性结肠炎均有显著改善作用,葛根芩连片仅对急性结肠炎有显著疗效。     

Effect of Hypericum perforatum L. Extract on Insulin Resistance and Lipid Metabolic Disorder in High‐Fat‐Diet Induced Obese Mice

Natural product Hypericum perforatum L. has been used in folk medicine to improve mental performance. However, the effect of H. perforatum L. on metabolism is still unknown. In order to test whether H. perforatum L. extract (EHP) has an effect on metabolic syndrome, we treated diet induced obese (DIO) C57BL/6J mice with the extract. The chemical characters of EHP were investigated with thin‐layer chromatography, ultraviolet, high‐performance liquid chromatography (HPLC), and HPLC‐mass spectrometry fingerprint analysis. Oral glucose tolerance test (OGTT), insulin tolerance test (ITT), and the glucose infusion rate (GIR) in hyperinsulinemic–euglycemic clamp test were performed to evaluate the glucose metabolism and insulin sensitivity. Skeletal muscle was examined for lipid metabolism. The results suggest that EHP can significantly improve the glucose and lipid metabolism in DIO mice. In vitro, EHP inhibited the catalytic activity of recombinant human protein tyrosine phosphatase 1B (PTP1B) and reduced the protein and mRNA levels of PTP1B in the skeletal muscle. Moreover, expressions of genes related to fatty acid uptake and oxidation were changed by EHP in the skeletal muscle. These results suggest that EHP may improve insulin resistance and lipid metabolism in DIO mice. © 2014 The Authors. Phytotherapy Research published by John Wiley & Sons Ltd.