雷公藤多甙预防nonobese diabetic(NOD)小鼠1型糖尿病的机理研究

目的观察雷公藤多甙(TWP)对nonobese diabetic(NOD)小鼠1型糖尿病的免疫预防作用及机理。方法采用NOD小鼠环磷酰胺加速发病,给TWP后观察血糖、糖尿病发病率、胰岛炎变化,半定量RT-PCR分析胰腺组织干扰素γ(IFN-γ)、肿瘤坏死因子α(TNF-α)、白介素10(IL-10)mRNA的表达。结果TWP组实验结束时血糖均值(10．73 mmol/L)低于对照组(20．53 mmol/L)(P＜0．01)；糖尿病发病率(43．33%)也低于对照组(71．43%)(P＜0．01)；胰岛炎评分1．45±1．11,低于对照组(2．27±1．22,P＜0．05)；TWP组胰岛素阳性细胞数为242．80±168．93,对照组胰岛素阳性细胞数为95．60±39．55,两者差异显著(P＜0．05)。胰腺组织IFN-γ、TNF-αmRNA的表达降低(P＜0．01),IL-10mRNA的表达无明显改变。结论TWP可预防NOD鼠糖尿病的发生,其机制可能与下调胰腺组织Th1细胞因子表达有关。     

玉竹对STZ诱导的1型糖尿病小鼠的降糖作用

目的:探讨玉竹对链脲佐菌素(STZ)诱导的1型糖尿病小鼠的降糖作用及其可能的作用机制。方法:采用多次小剂量STZ(mlD-STZ)腹腔注射的方法建立1型糖尿病小鼠模型。玉竹提取物8,4,2g/kg剂量组分别按相应剂量用玉竹提取物灌胃,糖尿病模型组和正常对照组用蒸馏水灌胃0.2ml/只,1次/d,共4周。每周剪尾取血1次,用快速血糖仪监测血糖变化。四周后将小鼠处死取胰腺做HE染色,光镜下观察胰腺病理学改变;采用酶联免疫分析(ELISA)法检测小鼠脾细胞上清液中IFN-γ和IL-4水平。结果:与糖尿病模型组相比,玉竹提取物8g/kg和4g/kg剂量组小鼠血糖明显降低(P<0.01)、胰岛炎程度明显缓解、脾细胞上清液中IFN-γ水平和IFN-γ/IL-4比值明显降低(P<0.05～0.01),而2g/kg剂量组小鼠上述指标变化不明显;各组小鼠脾细胞上清液中IL-4水平差异无统计学意义。结论:玉竹提取物能明显降低STZ诱导的1型糖尿病小鼠的血糖,其降糖机制可能与抑制1型糖尿病小鼠Th1细胞的极化程度,减轻细胞免疫功能对胰岛β细胞的破坏有关。     

中国被毛孢对MOG_(35-55)诱导小鼠实验性自身免疫性脑脊髓炎的治疗作用

目的:观察中国被毛孢对髓鞘少突胶质细胞糖蛋白(myelin oligodendrocyte glycoprotein MOG_(35-55))诱导小鼠实验性自身免疫性脑脊髓炎(experimental autoimmune encephalomyelitis,EAE)的治疗作用。方法:用MOG_(35-55)免疫C57BL/6小鼠诱导产生EAE模型,观察4.0 g/kg中国被毛孢对EAE小鼠体质量、神经功能、Bcl-2/Bax蛋白表达和脊髓病理组织的变化。结果:小鼠经MOG_(35-55)诱导后,模型小鼠均出现临床症状,死亡率为62.5%;给予4.0 g/kg中国被毛孢后,在给药第14～16天时体质量明显重于模型对照组,平均神经症状评分明显降低(P0.05,P0.01),死亡率为12.5%,脊髓中Bax和Bcl-2蛋白表达分别明显降低和明显升高(P0.05),髓鞘脱失范围及程度显著减少。结论:中国被毛孢对MOG_(35-55)诱导小鼠EAE发病有一定的治疗作用。     

电针“胃脘下俞”对2型糖尿病大鼠胰岛形态及胰腺胰高血糖素样肽1受体的影响

目的:观察电针对2型糖尿病大鼠胰腺胰高血糖素样肽1受体(GLP-1R)及胰腺十二指肠同源盒基因(PDX-1)蛋白表达及空腹血糖的影响,探讨电针"胃脘下俞"干预2型糖尿病的作用机制。方法:SD大鼠依据空腹血糖随机区组分为空白组、模型组、电针胃脘下俞组、电针心俞组、电针肾俞组,每组各12只。以高糖高脂饲料喂养结合2%链脲佐菌素(35mg/kg)腹腔注射制备2型糖尿病模型。各电针组分别电针双侧"胃脘下俞""心俞"及"肾俞",每周治疗6次,共治疗4周。以罗氏血糖仪检测治疗前后空腹血糖,HE染色、Masson染色观察胰腺形态学变化,Western blot法检测胰腺GLP-1R及PDX-1蛋白表达。结果:造模后各组大鼠空腹血糖均明显高于空白组(P0.01),电针"胃脘下俞"可显著降低大鼠的空腹血糖(P0.05)。模型组大鼠胰岛形态不规则,胰岛面积、胰岛β细胞核数量减少,胰岛β细胞核代偿性增大;电针"胃脘下俞""心俞""肾俞"均可在一定程度上恢复胰岛形态和面积及胰岛β细胞核数量,缓解胰岛β细胞核代偿性增大。模型组胰腺GLP-1R蛋白表达显著低于空白组(P0.01),电针"胃脘下俞""心俞""肾俞"均可显著提高胰腺GLP-1R蛋白表达(P0.01,P0.05),电针"心俞"后胰腺GLP-1R蛋白表达明显高于电针"胃脘下俞"(P0.05)及"肾俞"(P0.01),电针胃脘下俞组高于电针肾俞组(P0.05)。模型组胰腺PDX-1蛋白表达量显著低于空白组(P0.01),电针"胃脘下俞""心俞""肾俞"均未见明显变化(P0.05)。结论:电针"胃脘下俞"可能通过调节胰腺功能,提高胰腺GLP-1R表达,部分恢复胰岛形态,起到降低血糖的作用。     

镰形棘豆总黄酮对2型糖尿病KKAy小鼠血糖和胰岛素抵抗的作用

目的:以糖尿病KKAy小鼠为研究对象,观察镰形棘豆总黄酮对2型糖尿病KKAy小鼠胰岛素抵抗的作用。方法:将40只雄性SPF级KKAy小鼠随机分为5组,分别为模型组、镰形棘豆总黄酮低、中、高剂量组、阳性药组,每组8只;另选8只C57BL/6J小鼠为正常组。正常组和模型组ig生理盐水,镰形棘豆总黄酮低、中、高剂量组,分别按100,200,400 mg·kg-1·d-1剂量ig,阳性药组ig吡咯列酮10 mg·kg-1·d-1。连续4周。每周监测小鼠体重、空腹血糖和餐后血糖。4周后,眼眶静脉取血,离心取血清;取胰腺组织。采用酶联免疫吸附测定(ELISA)法检测小鼠空腹胰岛素水平,并计算胰岛素分泌指数(ISI),胰腺组织苏木素-伊红(HE)染色后光镜下观察胰岛结构变化。结果:与正常组比较,模型组KKAy小鼠空腹血糖明显升高,餐后2 h血糖明显升高,胰岛素水平明显升高,胰岛素敏感指数明显降低(P0.05),模型组KKAy小鼠胰腺组织病变较为明显;镰形棘豆总黄酮对降低糖尿病小鼠体重作用不明显,与模型组比较,在ig 7,28 d时,空腹血糖明显降低,在ig 14 d后,餐后2 h血糖明显降低(P0.05),在治疗28 d后,与模型组比较,镰形棘豆总黄酮高剂量具有促进胰岛素分泌的作用;中剂量组具有增强胰岛素敏感性的作用(P0.05),HE染色显示各药物组具有保护胰岛β细胞、延缓胰岛衰竭的作用。结论:镰形棘豆总黄酮在一定程度上具有降低2型糖尿病小鼠血糖,促进胰岛素分泌,改善胰岛素抵抗的作用。     

丹酚酸B对糖尿病血糖波动模型大鼠胰岛细胞的保护作用

目的观察丹酚酸B对糖尿病血糖波动模型大鼠胰岛细胞的保护作用,并探讨其可能的作用机制。方法采用高糖高脂饮食合并ip链脲佐菌素(STZ)的方法建立大鼠糖尿病模型,并在此基础上通过错时给予胰岛素或葡萄糖建立糖尿病血糖波动模型,丹酚酸B各组分别给予丹酚B 160、80 mg/kg。血糖波动6周后,检测大鼠空腹血糖(FBG)、空腹胰岛素(FINS)和糖化血红蛋白(GHb)水平,并检测大鼠血清和胰腺组织总抗氧化能力(TAC)、超氧化物歧化酶(SOD)活性和丙二醛(MDA)水平,HE染色法观察大鼠胰岛组织病理学改变,TUNEL染色法检测大鼠胰岛细胞凋亡情况,Western blotting法检测胰腺组织胰十二指肠同源盒-1(PDX-1)蛋白表达水平。结果糖尿病大鼠FBG、GHb及血清和胰腺组织MDA水平较对照组明显升高,而FINS水平及血清和胰腺组织TAC、SOD活性显著下降(P0.01)。同时,糖尿病大鼠胰岛数量减少,胰岛体积缩小,胰岛细胞凋亡明显增多(P0.01),胰腺组织PDX-1蛋白表达水平显著下降(P0.01)。给予丹酚酸B 6周后,大鼠FINS水平,血清及胰腺组织中TAC、SOD活性均明显升高,而FBG、GHb、血清及胰腺组织中MDA水平明显下降(P0.05、0.01)。丹酚酸B明显改善大鼠胰岛病理学改变,减少胰岛细胞凋亡,增加PDX-1蛋白表达水平(P0.05、0.01)。结论丹酚酸B可明显减轻糖尿病血糖波动模型大鼠胰岛病变,改善胰岛功能,其作用机制可能与改善氧化应激、上调PDX-1蛋白表达水平,进而抑制胰岛细胞凋亡有关。     

降糖消脂片对KK-Ay转基因小鼠胰岛素抵抗的影响

目的观察降糖消脂片对KK-A~y转基因小鼠稳态模型评估胰岛素抵抗指数(homeostasis model assessment for insulin resistance index,HOMA-IR)、胰岛素敏感指数(insulin sensitivity index,ISI)、胰腺组织胰岛素(insulin,INS)及胰岛素受体(insulin receptor,InsR)蛋白表达的影响。方法采用高脂饲料喂养KKAy转基因小鼠,制备糖尿病肥胖小鼠模型。同时选取11只同龄C57小鼠作为正常对照。将成模的55只KK-A~y小鼠采用随机数字表法分为模型组、吡格列酮组(8 mg/kg)、降糖消脂片高、中、低剂量组(分别给予降糖消脂片10、5、2.5 g生药/kg),每组11只。以上各组均灌胃给药,正常对照组及模型组灌胃等体积灭菌水,每日1次,连续8周。给药8周后,称体重并测随机血糖(random blood glucose,RBG);眼静脉丛取血,测定INS、TC及TG水平,计算HOMA-IR及ISI;取胰腺进行形态学观察;采用免疫组化方法检测胰腺组织INS及InsR表达;采用免疫印迹(Western blot)法检测胰腺胰岛素受体β(insulin receptorβ,InsRβ)及胰岛素受体底物1(insulin receptor substrate 1,IRS-1)蛋白表达水平。结果与正常对照组比较,造模后各组小鼠出现肥胖,血糖及血脂明显升高(P0.01)。给药8周后模型组小鼠体重增加(P0.01),血糖及血脂稳定在高位水平;与模型组比较,降糖消脂片各剂量组小鼠体重、TG、INS及HOMA-IR水平明显降低(P0.05,P0.01);且高剂量组RBG降低更明显(P0.01);降糖消脂片高、低剂量组小鼠ISI明显升高(P0.05,P0.01)。胰腺病理HE染色结果显示,模型组胰岛萎缩,胰岛数目明显减少,分布稀疏,胰岛密度减低,胰岛细胞代偿性肥大,空泡变性,并可见凋亡细胞,表现为胞浆肿胀,核固缩。降糖消脂片高、中剂量组胰岛细胞数目明显增多,变性及凋亡细胞减少。免疫组化结果显示,与正常对照组比较,模型组INS及InsR累积光密度(IOD)值明显降低(P0.01);与模型组比较,降糖消脂片各剂量组胰腺INS及InsR IOD值明显增加(P0.05,P0.01)。Western blot结果显示,与正常对照组比较,模型组InsRβ及IRS-1蛋白表达明显降低(P0.01);与模型组比较,降糖消脂片各剂量组InsRβ及IRS-1蛋白表达水平升高(P0.01),与吡格列酮组比较,差异无统计学意义(P0.05)。结论降糖消脂片对KK-A~y糖尿病肥胖小鼠有明显的降糖、降脂及改善胰岛素抵抗的作用,其机理可能是通过增加胰岛细胞InsRβ及IRS-1表达,促进INS与受体的结合,从而改善糖、脂代谢和IR状态。     

金荞麦叶茶抗2型糖尿病的作用及机制研究

目的探讨金荞麦叶茶对实验性2型糖尿病小鼠血脂、血糖的影响、体内抗氧化活性以及肝脏、胰腺损伤的保护作用。方法采用四氧嘧啶诱导加高脂高热量饲料喂养的方法建立小鼠2型糖尿病模型,血糖仪检测各组小鼠的空腹血糖,氧化酶法测定血清总胆固醇(TC)、甘油三酯(TG)、高密度脂蛋白(HDL-C)和低密度脂蛋白(LDL-C)的变化及测定超氧化物歧化酶(SOD)水平、丙二醛(MDA)含量,并在光镜下观察小鼠胰腺和肝脏形态学改变。结果治疗组小鼠血糖、血脂有下降趋势、MDA的活力明显降低(P0.05),而SOD活力显著提高(P0.05),并可改善2型糖尿病小鼠的胰腺、肝脏病变。结论金荞麦叶茶可以降低2型糖尿病小鼠血糖、TC、TG,可能与其清除自由基,抗脂质过氧化作用有关,对2型糖尿病小鼠胰腺、肝脏损伤具有一定保护作用。     

艾叶多糖I型糖尿病小鼠的降血糖作用

目的研究艾叶多糖对I型糖尿病小鼠的降血糖作用。方法采用腹腔注射链脲佐菌素的方法建立I型糖尿病小鼠模型,灌胃给予糖尿病模型小鼠艾叶多糖(100,200和400 mg·kg-1·d-1),连续30d,观察糖尿病小鼠的血糖以及糖耐量的变化,比色法和ELISA法分别测定肝糖原以及血清胰岛素水平。灌胃给予健康大鼠艾叶多糖(100,200和400 mg·kg-1)后提取含药血浆,与大鼠胰岛细胞体外共孵育,ELISA法测定培养上清液中胰岛素含量。结果艾叶多糖能明显降低糖尿病小鼠的血糖浓度,改善糖耐量,还能显著增加肝糖原存储量(P0.05),100和200 mg·kg-1·d-1剂量的艾叶多糖还能提高血清胰岛素水平(P0.05,P0.01),但艾叶多糖对胰岛细胞分泌胰岛素无影响。结论艾叶多糖能增加糖尿病小鼠的肝糖原、改善胰岛素分泌,调节血糖浓度。     

地锦草对糖尿病小鼠胰岛β细胞氧化应激和凋亡的影响

目的:研究地锦草对糖尿病小鼠胰岛β细胞氧化应激和凋亡的影响。方法:尾静脉注射四氧嘧啶溶液(80 mg·kg-1)复制糖尿病小鼠模型。将造模成功的小鼠随机分为5组:模型组,阳性对照组(盐酸二甲双胍悬浊液25 mg·kg-1·d-1),地锦草低、中、高剂量组(59,118,236 mg·kg-1·d-1),连续给药14 d后,观察其血糖、胰腺组织超氧化物歧化酶(SOD),谷胱甘肽过氧化物酶(GSH-Px),丙二醛(MDA)水平的变化,采用末端脱氧核苷酸转移酶介导的d UTP缺口末端标记法(TUNEL法)检测胰岛β细胞的凋亡情况。结果:与模型组比较,地锦草各剂量组小鼠体重下降不明显(P0.05);与给药前及模型组比较,地锦草高剂量组和二甲双胍组血糖均下降(P0.05);与模型组比较,地锦草高剂量组和二甲双胍组胰腺组织中SOD和GSH-Px活性均升高(P0.05),MDA的含量降低(P0.05),胰岛β细胞凋亡指数降低(P0.05)。结论:地锦草可明显降低糖尿病小鼠的血糖,其机制可能与增强糖尿病小鼠的抗氧化能力,减弱氧化应激对糖尿病小鼠胰岛β细胞的损伤,抑制胰岛β细胞的凋亡有关。     

Glutathione S-transferases and malondialdehyde in the liver of NOD mice on short-term treatment with plant mixture extract P-9801091

Changes in the concentration of glutathione S-transferases (GSTs) and malondialdehyde (MDA) were assessed in the liver of normal and diabetic NOD mice with and without treatment with the plant extract P-9801091. The plant extract P-9801091 is an antihyperglycaemic preparation containing Myrtilli folium (Vaccinium myrtillus L.), Taraxaci radix (Taraxacum of fi cinale Web.), Cichorii radix (Cichorium intybus L.), Juniperi fructus (Juniperus communis L.), Centaurii herba (Centaurium umbellatum Gilib.), Phaseoli pericarpium (Phaseolus vulgaris L.), Millefoliiherba (Achillea millefolium L.), Mori folium (Morus nigra L.), Valerianae radix (Valeriana of ficinalis L.) and Urticae herba et radix (Urtica dioica L). Hyperglycaemia in diabetes mellitus is responsible for the development of oxidative stress (via glucose auto-oxidation and protein glycation), which is characterized by increased lipid peroxide production (MDA is a lipid peroxidation end product) and/or decreased antioxidative defence (GST in the liver is predominantly an alpha enzyme, which has antioxidative activity). The catalytic concentration of GSTs in the liver was significantly reduced in diabetic NOD mice compared with normal NOD mice (p < 0.01), while the concentration of MDA showed a rising tendency (not significant). The results showed that statistically significant changes in antioxidative defence occurred in the experimental model of short-term diabetes mellitus. A 7-day treatment with P-9801091 plant extract at a dose of 20 mg/kg body mass led to a significant increase in the catalytic concentration of GSTs in the liver of diabetic NOD mice (p < 0.01) and a decrease in MDA concentration (not significant), which could be explained by its antihyperglycaemic effect.     

Japanese herbal medicine TJ-48 prevents autoimmune diabetes in NOD mice

Type 1 diabetes mellitus (T1DM) is mainly caused by CD8(+) cytotoxic T cell infiltration into islets. Recently, the role of regulatory T cells (Tregs) in the prevention of the onset of T1DM was reported. We reported that TJ-48, a common Japanese herbal medicine, decreased Treg population in cancer patients, thus we investigated whether TJ-48 had an influence on T1DM onset using NOD mice. In the TJ-48 group, TJ-48 (2.0g/kg/day) was administered in the drinking water for NOD mice from three weeks of age to 20 weeks of age. Their body weight and fast blood glucose (FBG) were measured every week. Histology (Hematoxylin-Eosin staining) was investigated every month. Lymphocyte profiles were investigated every month with FACS. The results were compared to the age-matched NOD mice control group. FBG of the control group mice showed diabetic status of 66.7% at 18 weeks of age. On the other hand, the TJ-48 group mice showed diabetic status of 16.7% at 18 weeks of age (p = 1.905E-06). There were no significant differences in general conditions or body weight between the two groups. Lymphocyte infiltrations into islets were dramatically suppressed in the TJ-48 group. The effect of TJ-48 on decreasing Tregs was less apparent in the NOD mice model. TJ-48 inhibited lymphocyte infiltrations into islets, which led to preventing the onset of T1DM in NOD mice.     

Total coumarins from Urtica dentata Hand prevent murine autoimmune diabetes via suppression of the TLR4-signaling pathways

Ethnopharmacological relevance

Urtica dentata Hand (UDH), the root of Laportea bulbifera (Sieb. et. Zucc.) Wedd, has been traditionally used in traditional Chinese medicine as an anti-inflammatory and immuno-regulatory agent for rheumatoid arthritis and some other autoimmune diseases treatment. And the coumarins are the major components of UDH.

Aim of the study

To investigate the effect of total coumarins (TC) isolated from UDH on the development of autoimmune diabetes.

Materials and methods

Eight-week-old non-obese diabetic (NOD) mice were randomly divided into four groups: control group, low-dose (37.5 mg/kg), middle-dose (75 mg/kg), and high-dose (150 mg/kg) TC-treatment groups. NOD mice were then given with a suspension of TC or saline by intragastric (i.g.) administration every other day. After 4 weeks of treatment, 8 mice at 12-weeks of age per group were randomly selected to be sacrificed to perform intraperitoneal glucose tolerance test, examine histopathological insulitis, spleen T lymphocyte proliferation, the percentage of CD4+CD25+Foxp3+ T regulatory cell (Treg), dendritic cell (DC) surface molecules, toll-like receptor (TLR)4 expression and signal pathways involved. The remaining 10 mice per group were kept until 26 weeks of age to assess the incidence of diabetes. We also studied the direct effect of TC on DC and CD4+CD25+ Tregs in vitro.

Results

Treatment with TC for 4 weeks significantly inhibited insulitis, increased pancreatic islet number, delayed the onset and decreased the development of diabetes by 26 weeks of age in NOD mice, compared with the untreated control mice. TC suppressed spleen T lymphocyte proliferation, induced Th2-biased cytokine response, the generation of CD4+CD25+Foxp3+ Tregs and Foxp3 mRNA expression. And TC-treated DCs were characterized as low expression of MHC class II and CD86 molecules. TLR4 gene and protein expressions in the spleen, thymus and pancreas were down-regulated in TC-treated groups. The key molecules in the downstream signaling cascades of TLR4, including myeloid differentiation factor (MyD)88, nuclear factor (NF)-κB, IL-1β, Toll–IL-1 receptor domain-containing adaptor inducing interferon-β(TRIF), TRIF-related adaptor molecule (TRAM), interferon regulatory factor (IRF)-3 and IFN-β, all decreased significantly in TC groups, suggesting that TC inhibits both MyD88-dependent and -independent pathways of TLR4. At the cellular level, however, TLR4 protein expression in DCs, but not in Tregs, was downregulated by TC. And TC strengthened the role of DC, not Treg, in negative immune regulation in vitro. In contrast, anti-TLR4 antibody could block the effect of TC on DCs immune function.

Conclusion

These results suggest that TC extracted from UDH prevent the development of autoimmune diabetes in NOD mice via suppression of the TLR4-signaling pathways. TC maintain the DCs in an immature tolerogenic state, at least in part, mediated by down-regulating TLR4-signaling pathways in DCs, then enhance Treg differentiation, shift toward Th2 and suppress T lymphocyte proliferation.     

Effect of 'antidiabetis' herbal preparation on serum glucose and fructosamine in NOD mice

The antihyperglycemic effect of the Antidiabetis herbal preparation ((Myrtilli folium (Vaccinium myrtillus L.), Taraxaci radix (Taraxacum officinale Web.), Cichorii radix (Cichorium intybus L.), Juniperi fructus (Juniperus communis L.), Centaurii herba (Centaurium umbellatum Gilib.), Phaseoli pericarpium (Phaseolus vulgaris), Millefollii herba (Achillea millefolium L.), Morii folium (Morus nigra L.), Valeriane radix (Valleriana officinalis L.), Urticae herba et radix (Urtica dioica L.)), patent No. P-9801091 Zagreb, Croatia was investigated. Two extracts were prepared: ethanol extract (extract 1), and ethanol extract from which ethanol was evaporated on a rotatory evaporator at a temperature of 45 degrees C (extract 2). Extract 1 and extract 2 were administered (in experiment 1) to alloxan-induced non-obese diabetic (NOD) mice in the same dose of 20 mg/kg. Blood glucose was determined before, and 10, 30, 60 and 120 min after the preparation administration. Extract 1 and extract 2 decreased the level of blood glucose by 10 and 20%, respectively, of the initial value (at 0 min, mean = 22.6 +/- 8.3 mmol/l). Serum levels of glucose and fructosamine were determined in NOD mice, NOD mice administered extract 2 in a dose of 20 mg/kg of extract 2, and NOD mice administered acarbose in a dose of 25 mg/100 g chow, in order to verify the hypoglycemic action of extract 2 (in experiment 2). Extract 2 and acarbose were admixed to the chow. The duration of treatment was 7 days. Significantly lower glucose (P < 0.05) and fructosamine (P < 0.001) levels were recorded in extract 2 treated NOD mice as compared with NOD mice. Study results showed extract 2 to significantly decrease the level of glucose and fructosamine in alloxan induced NOD mice. Our future studies will be focused on the search of active principles of the extracts.     

Cytopiloyne, a novel polyacetylenic glucoside from Bidens pilosa, functions as a T helper cell modulator

An extract of Bidens pilosa, an anti-diabetic Asteraceae plant, has recently been reported to modulate T cell differentiation and prevent the development of non-obese diabetes (NOD) in NOD mice. In this paper, a novel bioactive polyacetylenic glucoside, cytopiloyne (1), was identified from the Bidens pilosa extract using ex vivo T cell differentiation assays based on a bioactivity-guided fractionation and isolation procedure. Its structure was elucidated as 2β-d-glucopyranosyloxy-1-hydroxytrideca-5,7,9,11-tetrayne by various spectroscopic methods. Functional studies showed that cytopiloyne was able to inhibit the differentiation of naïve T helper (Th0) cells into type I T helper (Th1) cells but to promote the differentiation of Th0 cells into type II T helper (Th2) cell. Accordingly, cytopiloyne also suppressed IFN-γ expression and promoted IL-4 expression in mouse splenocytes ex vivo. These results suggest that cytopiloyne functions as a T cell modulator that may directly contribute to the ethnopharmacological effect of Bidens pilosa extract on preventing diabetes. Moreover, cytopiloyne can serve as an index compound for quality control of lot-to-lot extract preparations of Bidens pilosa.     

从黄芩苷对TLRs-NOD2的调控探讨肺、脑相关炎性反应的共同机制

目的：通过研究黄芩苷对脑缺血和肺炎模型中TLRs-NOD2受体的影响,探讨肺、脑相关炎性病变的共同机制。方法：分别建立小鼠脑缺血再灌和急性肺炎模型,造模后对小鼠腹腔注射黄芩苷,检测小鼠脑和肺组织中TLR2/4、NOD2和TNFα蛋白的表达。结果：脑损伤模型小鼠脑组织和肺组织中,TLR2/4、NOD2和TNFα显著高表达,黄芩苷能够不同程度的下调这些因子;肺炎模型小鼠脑组织和肺组织中,TLR2/4、NOD2和TNFα不同程度的高表达,黄芩苷可以在不同程度上抑制这些因子。结论：黄芩苷对TLR2/4、NOD2受体及下游炎性因子TNFα存在着显著的调控作用,这种调控作用及对炎性反应的影响可能是其对肺、脑病变作用的共同基础。     

降压药物对新发糖尿病影响的网络Meta分析

 目的 综合评价利尿剂、β受体阻滞剂、血管紧张素转换酶抑制剂(ACEI)、血管紧张素Ⅱ受体阻滞剂(ARB)和钙通道阻滞剂(CCB)5类降压药物对新发糖尿病(NOD)的影响。方法 检索有关降压药物和NOD的临床试验,在WinBUGS 1.4.3软件中构建随机效应贝叶斯模型,估计这5类药物以及安慰剂之间的OR值及其优劣顺序。结果 共纳入28项临床试验,将安慰剂作为被比较者,OR值分别为:ARB 1.23(95%CI:1.087~1.399),ACEI 1.204(95%CI:1.033~1.424),CCB 0.928 9(95%CI:0.779 3~1.095),β受体阻滞剂 0.738 4(95%CI:0.604 7~0.890 6),利尿剂 0.789 4(95%CI:0.654~0.928 3)。其中,ARB引发NOD的概率最低,其后依次为ACEI、安慰剂、CCB、利尿剂和β受体阻滞剂。结论 ARB、ACEI会减少NOD发生的风险,而CCB、利尿剂和β受体阻滞剂会增加NOD发生的风险。     

活血解毒方干预NOD小鼠自发性干燥综合征的机制研究

目的探讨活血解毒方对非肥胖糖尿病（NOD）自发性干燥综合征（ss）小鼠的疗效及作用机制。方法将18只NOD／Ltj小鼠随机分为模型组、活血解毒方组、白芍总苷组各6只,并设6只C57BL／6J小鼠作为正常组,灌胃8周后取小鼠颌下腺及血清分别采用反转录-聚合酶链反应（RT-PCR）法和ELISA法检测Toll样受体TLR4、CD14的mRNA和蛋白表达。结果与正常组比较,模型组TLR4、CD14的mRNA和蛋白表达明显升高,差异有统计学意义（P〈0．05）;与模型组比较,白芍总苷组、活血解毒方组TLR4、CD14的mRNA和蛋白表达水平均有降低,差异有统计学意义（P〈0．05）;白芍总苷组、活血解毒方组2组间比较,TLR4、CD14的mRNA和蛋白表达差异均无统计学意义（P〉0．05）。结论活血解毒中药对NOD小鼠SS具有较好的治疗作用,其作用机制可能与TLR4／CD14信号转导通路有关。     

蝎毒多肽干预急性白血病髓外浸润传变的机制

目的:观察蝎毒多肽(PESV)对人白血病NOD/SCID小鼠髓外浸润模型体内uPA、uPAR、MMP2、MMP9表达的影响,探讨PESV干预急性白血病髓外浸润传变的机制。方法:首先选取急性白血病患者骨髓单个核细胞注入经过铯-137源照射的NOD/SCID小鼠体内,建立人白血病NOD/SCID小鼠髓外浸润模型;对实验小鼠随机分组,用Real-time PCR及Western Blot检测PESV治疗后小鼠体内MMP2、MMP9 mRNA和蛋白表达水平,用ELISA法检测小鼠血清uPA及uPAR表达水平。结果:PESV能够抑制模型小鼠体内MMP2、MMP9 mRNA及蛋白水平表达,能够抑制uPA及uPAR过度表达,其抑制效果与PESV浓度具有相关性。结论:PESV通过干预细胞外基质降解机制,阻抑急性白血病髓外浸润传变进展。