厚朴丸对小鼠胃肠活动的影响

目的:观察厚朴丸对小鼠胃排空和小肠推进运动的影响.方法:利用胃复安和阿托品造成小鼠胃排空亢进和胃排空抑制模型,利用新斯的明和肾上腺素造成小鼠小肠推进亢进和小肠推进抑制模型,观察厚朴丸对正常、亢进及抑制状态下小鼠胃肠活动的影响.结果:厚朴丸抑制正常小鼠胃排空和胃复安所致小鼠胃排空加快,能加强阿托品所致小鼠胃排空的抑制作用;对正常小鼠小肠推进和新斯的明所致小鼠小肠推进亢进也有抑制作用,但对肾上腺素所致小鼠小肠推进抑制无明显影响.结论:厚朴丸具有抑制正常和亢进状态的小鼠胃排空和小肠推进的作用,与临床用于止泻相符合.     

无毒棉籽液抗腹泻作用研究

通过对正常小鼠、生大黄致泻小鼠及脾虚小鼠的作用研究表明，无毒棉籽液有较好的抑制排便频度、治疗腹泻的作用．无毒棉籽液６ｇ／ｋｇ可极其显著地抑制正常小鼠的排便频度，无毒棉籽液６ｇ／ｋｇ和３ｇ／ｋｇ可极其显著地抑制生大黄致泻小鼠及脾虚小鼠的排便频度．６ｇ／ｋｇ无毒棉籽液且可极其显著地抑制正常小鼠及脾虚小鼠的小肠推进运动．     

复方小建中冲剂药理研究

复方小建中冲剂显著抑制水应激性和消炎痛加乙醇诱发的小鼠胃溃疡，抑制０．６ｍｏｌ／Ｌ盐酸和结扎幽门引起的大鼠胃溃疡，溃疡抑制率为４１－８７％；并能抑制小鼠小肠推进性运动；抑制热和醋酸引起的小鼠痛反应；同时抑制二甲苯琼脂和角叉菜胶引起的小鼠、大鼠炎症反应。     

胍丁胺抑制小鼠吗啡戒断与其抑制一氧化氮合酶的关系(英文)

目的:观察胍丁胺抑制纳洛酮引起小鼠吗啡戒断跳跃与其抑制一氧化氮合酶(NOS)的关系,方法:用测定[~3H]胍氨酸浓度的方法确定NOS活性,结果:在体外胍丁胺底物竞争性抑制正常和吗啡依赖小鼠小脑、端脑和丘脑NOS活性,纳洛酮引起吗啡依赖小鼠戒断跳跃和小脑、端脑、丘脑NOS活性升高,用吗啡和胍丁胺共同处理小鼠显著抑制纳洛酮促使小鼠戒断跳跃和NOS活性升高的作用,咪唑克生抑制胍丁胺的此作用,结论:胍丁胺对纳洛酮引起戒断跳跃的抑制作用与其通过激活咪唑啉受体和底物竞争性抑制NOS活性相关。     

杨梅素对小鼠被动皮肤过敏反应的影响

目的研究杨梅素的抗过敏作用。方法采用小鼠同种、异种被动皮肤过敏反应(PCA)、右旋糖酐致小鼠全身瘙痒反应和2,4-二硝基氯苯(DNCB)所致小鼠耳廓皮肤迟发型超敏反应(DTH)实验,探讨杨梅素的抗过敏作用。结果杨梅素显著抑制小鼠同种、异种被动皮肤过敏反应和右旋糖酐引起的小鼠瘙痒反应,并能抑制DNCB诱导的DTH。结论杨梅素具有抗过敏作用,机制可能与抑制Ⅰ、Ⅳ型变态反应有关。     

木香动力胶囊内容物对小鼠胃排空的影响

目的考察木香动力胶囊内容物 (MuxiangDynamicsCapsuleinclusion ,MDCI)对小鼠胃排空的影响。方法灌胃给药 ,采用正常小鼠和阿托品、左旋麻黄碱致小鼠胃排空抑制模型 ,考察MDCI对胃排空的影响。结果MDCI对正常小鼠胃排空无明显影响 ,对阿托品、左旋麻黄碱造成的小鼠胃排空抑制有明显拮抗作用。结论木香动力胶囊内容物对阿托品、左旋麻黄碱负荷下胃排空抑制有一定的拮抗作用     

引流熊胆的抗炎免疫抑制作用

引流熊胆Ｉｇ能明显地抑制二甲苯、巴豆油所致小鼠耳壳肿胀．抑制小鼠腹腔毛细血管通透性．抑制角叉菜胶所致大鼠足肿胀及Ｐｒｅｕｎｄ完全性剂所致大鼠关节炎；对肾上腺、胸腺、脾脏及淋巴结重量无明显影响。抑制小鼠棉球肉芽肿增生，抑制小鼠单核巨噬细胞吞噬功能。表明引流熊胆具有抑制急、慢性及免疫性炎症作用和免疫抑制作用。引流熊胆还抑制大鼠热烫足肿胀．减少大鼠炎症部位ＰＧＥ２含量。提示引流熊胆的抗炎作用与抑制炎症部位的激肽类和ＰＧＥ２的合成与释放有关。     

不同剂量黄芪组方的拯阳汤对小鼠免疫功能的影响

目的探讨不同剂量黄芪(47.62%、15.87%、5.29%)组方拯阳汤对小鼠免疫功能的影响.方法建立受氢化可的松(HC)免疫抑制动物模型,采用MTT法检测腹腔巨噬细胞(MФ)的活性、ConA诱导的脾脏T淋巴细胞转化增殖;以YAC-1为靶细胞用LDH释放改良法测定小鼠脾脏NK细胞和LAK细胞毒活性.结果不同剂量黄芪组方的拯阳汤具有不同程度地拮抗HC对小鼠腹腔MФ的活性的抑制,拮抗HC对小鼠脾脏T淋巴细胞转化的抑制,拮抗HC对小鼠脾脏NK细胞和LAK细胞毒活性的抑制.结论拯阳汤具有拮抗HC对小鼠细胞免疫抑制的作用.     

川木香及其煨制品对小鼠胃排空及肠推进的影响

目的 研究川木香及其煨制品对小鼠肠推进和胃排窄的影响.方法 采用小肠炭末推进实验观察川木香及其煨制品对正常小鼠小肠运动及硫酸阿托品所致小鼠小肠抑制模型的影响,采用甲基橙胃残留率的方法观察二者对正常小鼠胃排空、新斯的明所致小鼠胃排空亢进和肾上腺素所致小鼠胃排空抑制的影响.结果 15、9 g·kg-1川木香及其煨制品可明显促进正常小鼠的小肠运动,并能拮抗硫酸阿托品所致小鼠的小肠抑制作用;可促进正常小鼠的胃排空,并对肾上腺素所致小鼠胃排空的抑制有明显的拮抗作用.其中,15 g·kg-1煨制品对新斯的明所致小鼠的胃排空亢进有明显的拮抗作用.结论 川木香及其煨制品对小鼠的胃肠运动有促进作用,煨制品对不同功能状态的小鼠胃排空有双向调节作用.     

抗BLyS抗体抑制BLyS诱导小鼠脾细胞增殖实验方法的优化

目的：建立BLyS抗体抑制BLyS作用下小鼠脾细胞增殖实验的方法。方法：首先通过DOE全因子实验验证BLyS能抑制脾淋巴细胞增殖后的凋亡,初步确定BLyS和刺激因子LPS的使用浓度、细胞密度及培养天数。然后进一步优化BLVS、Belinmmab和LPS的使用浓度、孵育方式、培养天数等条件,确定抗体抑制BLyS作用下小鼠脾细胞增殖实验的方法。结果：BLyS能抑制小鼠脾淋巴细胞增殖后的凋亡;Belimumab对BLyS作用下小鼠脾细胞的增殖有显著中和作用。结论：建立BLyS抗体抑制BLyS作用下小鼠脾细胞增殖实验的方法,为进一步研究人BLyS与自身免疫疾病治疗药物奠定了基础。     

Development of a stable camptothecin-resistant subline of P388 leukemia with reduced topoisomerase I content

A camptothecin-resistant subline of P388 leukemia (P388/CPT) was developed by repeated transplantation of P388 cells in mice treated with therapeutic doses of camptothecin. In mice bearing the resistant tumor, a maximally tolerated dose of camptothecin produced no net reduction in tumor cell burden, in contrast to a 5-log cell kill in the parental P388 (P388/S). The IC50 of camptothecin, as determined by colony formation assays of cultured cells, was 8 times greater for the cloned P388/CPT cell line than for P388/S. P388/CPT cells were not cross-resistant to other antineoplastic agents, including topoisomerase II inhibitors. The type I topoisomerases purified from P388/CPT and P388/S cells were identical with respect to molecular weight, specific activity, in vitro camptothecin sensitivity, and DNA cleavage specificity. Camptothecin induced fewer protein-associated DNA single-strand breaks in the resistant cells than in the wild-type P388 cells. Topoisomerase I mRNA, immunoreactivity, and extractable enzymatic activity were 2-4 times lower for P388/CPT cells than for P388/S cells. As resistance to camptothecin developed, topoisomerase I extractable activity decreased, concomitant with an increase in topoisomerase II extractable activity. Furthermore, the appearance of camptothecin resistance was associated with specific rearrangements of the topoisomerase I gene. These results suggest that development of resistance to inhibitors of topoisomerase I can occur by down-regulation of the target enzyme, thus reducing the production of lethal enzyme-mediated DNA damage. The enhanced topoisomerase II activity in these cells suggests that resistance to camptothecin may be overcome by co-treatment with topoisomerase II inhibitors.     

Moxifloxacin increases anti-tumor and anti-angiogenic activity of irinotecan in human xenograft tumors

Camptothecins (CPTs) are topoisomerase I inhibitors chemotherapeutic agents used in combination chemotherapy. We showed previously that combination of moxifloxacin (MXF) and CPT induced inhibitory effects on topoisomerase I activity, on proliferation of HT-29 cells in vitro and enhanced apoptosis, compared to CPT alone. Analysis of secretion of the pro-angiogenic factors IL-8 and VEGF showed significant reduction by MXF. Using a murine model of human colon carcinoma xenograft, we compared the effects of MXF/CPT in vitro to MXF/irinotecan combination in vivo. We show that the MXF/CPT inhibitory effects observed in vitro are reflected in the inhibition of the progressive growth of HT-29 cells implanted in SCID mice. Using caliper measurements, Doppler ultrasonography, image analyses and immunohistochemistry of nuclear proteins (Ki-67) and vascular endothelial cells (CD-31) we show that addition of MXF (45 mg/kg) to a relatively ineffective dose of irinotecan (20 mg/kg), results in a 50% and 30% decrease, respectively, in tumor size and a decrease in Ki-67 staining. Power Doppler Ultrasound showed a significant, pronounced decrease in the number of blood vessels, as did CD-31 staining, indicating decreased blood flow in tumors in mice treated with MXF alone or MXF/irinotecan compared to irinotecan. These results suggest that the combination of MXF/irinotecan may result in enhanced anti-neoplastic/anti-angiogenic activity.     

Ultrasound-responsive nanobubbles contained with peptide–camptothecin conjugates for targeted drug delivery

To improve the targeting delivery efficiency of anticancer drug to tumor sites, a new strategy combining cell-permeable peptide (CPP) and ultrasound was reported in this article. In this study, we devised and tested a strategy for functional payload delivery to cells by loading CPP–camptothecin conjugate (CPP–CPT) into nanobubble (CPP–CPT?NB). Here, CPP existing in the conjugation form of CPP and CPT was hidden in nanobubble to cloak the penetration activity of CPP. Meanwhile, local tumor ultrasound was utilized to achieve specific targeting of CPP–CPT to the tumor cells. The mean particle size of the prepared CPP–CPT?NB was ～200?nm, and the drug entrapment efficiency was >80%. Stimulated by ultrasound, over 90% of the entrapped CPP–CPTs would release from the nanobubbles. Subsequent research demonstrated that the CPP–CPT?NB showed effective cellular uptake and significant cytotoxic activity in HeLa cells in vitro. Additionally, after systemic administration in mice, CPP–CPT?NB with ultrasound showed a higher tumor inhibition effect in nude mice xenografted HeLa cells tumors and excellent body safety when compared with normal CPT injection group. In conclusion, the carrier constructed in this study would be a safe and efficiently drug delivery system for specific cancer treatment.     

Preparation of carboxy‐PEG‐PLA nanoparticles loaded with camptothecin and their body distribution in solid tumor–bearing mice

Carboxy‐polyethylene glycol‐poly(DL‐lactic acid) block copolymer was synthesized by reductive amination of carboxy‐polyethylene glycol‐amine and aldehyde‐ended poly(DL‐lactic acid). The obtained product, PA‐PEG‐CB, composed of pure carboxy‐polyethylene glycol‐poly(DL‐lactic acid) block copolymer and poly(DL‐lactic acid), was used to prepare nanoparticles loaded with camptothecin (CPT), designated CPT‐NP. CPT‐NP with 500–600 nm and approximately 1% (w/w) drug content were obtained by emulsification/evaporation, while nanoparticles with a drug content of only less than 0.1% (w/w) were prepared by dialysis. CPT‐NP produced by emulsification/evaporation were used for in vitro and in vivo studies. CPT‐NP released CPT gradually in phosphate‐buffered saline, pH 7.4, at 37°C over 48 h. Biodistribution profiles were compared between CPT‐NP and CPT solution after i.v. injection into mice bearing sarcoma 180 solid tumor. CPT‐NP retained CPT approximately 10 times more in plasma during the initial 8 h than CPT solution. The tumor level of CPT was more than 10 times higher with CPT‐NP for the observation period (24 h), though the CPT concentration in the liver and spleen was much higher with CPT‐NP. CPT‐NP may be useful for tumor localization of CPT. Drug Dev Res 70: 512–519, 2009. © 2009 Wiley‐Liss, Inc.     

Effect of oxymatrine on lipid metabolism regulated genes in liver of fat-induced insulin resistance in ApoE-/-mice北大核心CSCD

Aim To investigate the effect of oxymatrine on lipid metabolism regulated genes in liver in fat-induced insulin resistance in ApoE-/- mice. Methods Seventeen C57BL/6J male mice were selected in normal control group. Sixty-eight ApoE-/- mice with high fat diet for 16 weeks, were randomly divided into model group, oxymatrine low, middle and high dose groups. Then they were gavaged for 8 weeks. Body weight and general biochemical indicators were determined in mice. The mRNA and protein expression levels of LPL, FAT/CD36, CPT1, UCP2, SREBP-1 c, FAS and ACC were examined by real-time PCR and Western blot in the liver. Results Compared with model group, oxymatrine reduced body weight (BW) , fasting blood glucose (FBG), cholesterol (TC) , triglyceride (TG) , free fatty acids (FFA), fasting plasma insulin (FINS) and insulin resistance index(HOMA-IR) (P < 0. 05) , while improved glucose infusion rate (GIR) . Oxymatrine down-regulated the mRNA and protein expression of LPL, FAT/CD36, UCP2, SREBP-1c, FAS and ACC(P <0. 05) ,and up-regulated the mRNA and protein expression of CPT1 in varying degrees (P < 0. 05). Conclusion Oxymatrine can regulate the expression of lipid metabolism regulated genes in liver and improve insulin resistance in ApoE-/- mice induced by high fat diet.     

卡托普利对博来霉素诱导大鼠肺纤维化的影响

目的探讨博来霉素（bleomycin）中毒肺BLM纤维化机制及卡托普利对BLM中毒肺纤维化的干预作用。方法 60只SD大鼠随机分为3组：正常对照（control）组、单纯BLM染毒（BLM）组和BLM染毒卡托普利（captopril,CPT）治疗（BLM＋CPT）组。14 d后处死各组动物,记录肺系数;病理组织学检查。结果 BLM染毒后大鼠肺系数增大,肺泡炎、肺纤维化程度积分明显增高。CPT均明显减轻了大鼠肺损伤、肺纤维化程度。结论 CPT对BLM中毒大鼠肺损伤、肺纤维化程度有一定改善作用,可能与其抑制血管紧张素Ⅱ有关。     

二氢杨梅素经激活SIRT1-AMPK通路抑制高脂饮食诱导的肥胖小鼠肝脏脂质沉积

目的探究二氢杨梅素(dihydromyricetin,DHM)对高脂饮食诱导的肥胖小鼠肝脏脂质蓄积的作用及其机制。方法C57BL/6J小鼠60只,随机分为6组(n=10):①ND组:正常饲料;②ND+L-DHM组:正常饲料+低剂量DHM(125 mg·kg^-1·d^-1);③ND+H-DHM组:正常饲料+高剂量DHM(250 mg·kg^-1·d^-1);④HFD组:高脂饲料;⑤HFD+L-DHM组:高脂饲料+低剂量DHM;⑥HFD+H-DHM组:高脂饲料+高剂量DHM。记录小鼠体重;16周后,测空腹血脂;计算体脂重量;肝脏HE和油红O染色;荧光定量PCR和Western blot检测肝脏SIRT1、AMPK、ACC、FAS、SREBP-1和PPARα、CPT1的表达。结果与ND组相比,HFD组小鼠体重、体脂、血清TG、TC、HDL水平明显增加;肝脏内脂肪蓄积增加,肝脏SREBP-1c、FAS、ACC1表达增加,而PPARα、CPT1、SIRT1和AMPK表达下降。经DHM处理后,HFD小鼠上述指标发生逆转;但ND小鼠上述指标无明显改变。结论DHM可能通过激活SIRT1-AMPK通路抑制脂质合成,促进脂质分解,改善高脂饮食诱导的肥胖小鼠肝脏脂质沉积。     

Cryptotanshinone inhibits TNF-α-induced LOX-1 expression by suppressing reactive oxygen species (ROS) formation in endothelial cells

Cryptotanshinone (CPT) is a natural compound isolated from traditional Chinese medicine Salvia miltiorrhiza Bunge. In the present study, the regulatory effect and potential mechanisms of CPT on tumor necrosis factor alpha (TNF-α) induced lectin-like receptor for oxidized low density lipoprotein (LOX-1) were investigated. Human umbilical vein endothelial cells (HUVECs) were cultured and the effect of TNF-α on LOX-1 expression at mRNA and protein levels was determined by Real-time PCR and Western blotting respectively. The formation of intracellular ROS was determined with fluorescence probe CM-DCFH₂-DA. The endothelial ox-LDL uptake was evaluated with DiI-ox-LDL. The effect of CPT on LOX-1 expression was also evaluated with SD rats. TNF-α induced LOX-1 expression in a dose- and time-dependent manner in endothelial cells. TNF-α induced ROS formation, phosphorylation of NF-κB p65 and ERK, and LOX-1 expression, which were suppressed by rotenone, DPI, NAC, and CPT. NF-κB inhibitor BAY11-7082 and ERK inhibitor PD98059 inhibited TNF-α-induced LOX-1 expression. CPT and NAC suppressed TNF-α-induced LOX-1 expression and phosphorylation of NF-κB p65 and ERK in rat aorta. These data suggested that TNF-α induced LOX-1 expression via ROS activated NF-κB/ERK pathway, which could be inhibited by CPT. This study provides new insights for the anti-atherosclerotic effect of CPT.     

Antitumor effects with apoptotic death in human promyelocytic leukemia HL‐60 cells and suppression of leukemia xenograft tumor growth by irinotecan HCl

Irinotecan HCl (CPT‐11) is an anticancer prodrug, but there is no available information addressing CPT‐11‐inhibited leukemia cells in in vitro and in vivo studies. Therefore, we investigated the cytotoxic effects of CPT‐11 in promyelocytic leukemia HL‐60 cells and in vivo and tumor growth in a leukemia xenograft model. Effects of CPT‐11 on HL‐60 cells were determined using flow cytometry, immunofluorescence staining, comet assay, real‐time PCR, and Western blotting. CPT‐11 demonstrated a dose‐ and time‐dependent inhibition of cell growth, induction of apoptosis, and cell‐cycle arrest at G0/G1 phase in HL‐60 cells. CPT‐11 promoted the release of AIF from mitochondria and its translocation to the nucleus. Bid, Bax, Apaf‐1, caspase‐9, AIF, Endo G, caspase‐12, ATF‐6b, Grp78, CDK2, Chk2, and cyclin D were all significantly upregulated and Bcl‐2 was down‐regulated by CPT‐11 in HL‐60 cells. Induction of cell‐cycle arrest by CPT‐11 was associated with changes in expression of key cell‐cycle regulators such as CDK2, Chk2, and cyclin D in HL‐60 cells. To test whether CPT‐11 could augment antitumor activity in vivo, athymic BALB/c^nu/nu nude mice were inoculated with HL‐60 cells, followed by treatment with either CPT‐11. The treatments significantly inhibited tumor growth and reduced tumor weight and volume in the HL‐60 xenograft mice. The present study demonstrates the schedule‐dependent antileukemia effect of CPT‐11 using both in vitro and in vivo models. CPT‐11 could potentially be a promising agent for the treatment of promyelocytic leukemia and requires further investigation. © 2014 Wiley Periodicals, Inc. Environ Toxicol 30: 803–815, 2015.     

银杏叶提取物GBE50对HepG2细胞甘油三酯代谢的影响

目的观察银杏叶提取物GBE50对HepG2细胞内甘油三酯含量的影响以及甘油三酯代谢关键基因CPT1A表达的调节。方法检测GBE50对培养细胞HepG2甘油三酯含量的影响;测定GBE50处理HepG2细胞24 h后CPT1A酶活性,用定量PCR检测药物处理后CPT1A基因表达水平的改变,Western blot检测CPT1A蛋白表达。结果 GBE50可降低培养细胞HepG2内甘油三酯含量。同时可以促进细胞CPT1A基因的表达,且能增加CPT1A酶的活性。结论 GBE50可有效降低HepG2细胞内甘油三酯的含量,CPT1A基因表达量的改变可能是GBE50调节HepG2细胞内甘油三酯水平的机制之一。