海藻提取物拮抗重铬酸钾诱发小鼠骨髓微核的研究

目的 研究海藻提取物对重铬酸钾(K_2Cr_2O_7)诱发骨髓嗜多染红细胞(PCE)微核的影响。方法 进行小鼠骨髓细胞微核试验。结果 经口灌胃给予K_2Cr_2O_7可诱发骨髓PCE的微核率(MNF)显著增加(P<0.01);经口灌胃给予海藻提取物和K_2CrO_7,可使MNF呈剂量依赖性下降,当剂量达中、高剂量时,MNF下降显著(P<0.05和P<0.01)。结论 海藻提取物对K_2Cr_2O_7诱发小鼠PCE微核具有拮抗作用,这一结果在癌症的化学预防和治疗上具有一定的参考价值。     

放射增效剂9402号对小鼠小肠隐窝上皮细胞增敏作用的研究

目的观察9402号对小鼠小肠隐窝上皮细胞的增敏作用。方法制做小鼠小肠组织切片,镜下观察不同剂量点单纯照射组和加药照射组小鼠小肠再生隐窝数。结果各剂量点的单纯照射组小鼠小肠再生隐窝数与加药照射组相比均无明显差异,经统计学处理P>0.05。9402号与60Coγ射线联合作用,对小鼠小肠隐窝上皮细胞的增敏比为1.02。结论9402号对正常小肠粘膜隐窝上皮细胞无明显增敏作用。     

1,2-二氯乙烷致小鼠血淋巴细胞遗传毒性研究

目的研究1,2-二氯乙烷(1,2-DCE)对小鼠血淋巴细胞DNA和骨髓细胞染色体的损伤作用,探讨1,2-二氯乙烷的遗传毒性。方法采用单细胞凝胶电泳和微核试验方法,分别检测1,2-DCE不同染毒剂量(50,100,200,400 mg/kg)小鼠外周血淋巴细胞DNA和骨髓细胞染色体损伤情况。结果除50 mg/kg剂量组外,小鼠血淋巴细胞的彗星细胞率及尾长、骨髓细胞微核率随1,2-DCE染毒剂量的增加而增加(P<0.01)。其中,400 mg/kg剂量组彗星细胞率、平均尾长、微核率分别为45.5%,(37.24±3.17)μm,12.0‰,显著高于阴性对照组和50 mg/kg剂量组(P<0.01)。染毒剂量与彗星细胞率、平均尾长、微核率之间存在着剂量-反应关系(R彗星率=0.980 2,R彗尾长=0.976 6,R微核率=0.975 1,P<0.01)。结论1,2-DCE可导致小鼠血淋巴细胞DNA损伤和骨髓细胞染色体异常。表明1,2-DCE具有细胞遗传毒性。     

饮茶对大鼠大肠变性隐窝病灶及大肠肿瘤的影响

以二甲基肼诱发Wistar大鼠大肠癌为模型,研究了绿茶和茶色素(红茶的主要成分)大肠癌的化学预防作用和对大肠肿瘤的影响。结果表明,在第16周2个饮茶组动物的变性隐窝病灶(ACF)形成数比阳性对照组显著减少(P< 0.01);在第32周时阳性对照组100% 发生了肿瘤(平均瘤数为2.6个/只,平均瘤体积为294.7m m 3/瘤)。绿茶组和茶色素组的平均瘤数抑制率分别为47.1% 和43.1% ,平均瘤体积抑制率分别为77.1% 和68.1% 。表明绿茶和茶色素对实验性大肠肿瘤具有预防作用,ACF作为一个有用的中间终点可代替癌发生率进行大肠癌化学预防剂研究     

温室土壤有机提取物遗传毒性研究

[目的]检测温室土壤中有机提取物的遗传毒性作用. [方法]以小鼠为实验动物,共分5组:阴性对照组(二甲亚砜)、阳性对照组(环磷酰胺)及土壤有机提取物低、中、高剂量组,染毒剂量分别为5、15和30g土壤干重/(kg小鼠体重·d),染毒方式为每日灌胃1次,连续染毒4周.用胞质分裂阻滞微核细胞试验和彗星试验分别检测有机提取物所致小鼠外周血淋巴细胞的染色体损伤作用和外周血细胞的DNA损伤作用. [结果]有机提取物剂量与微核率具有较明显的剂量-效应关系,显著高于阴性对照组;随着有机提取物作用剂量的增加,彗星尾长、尾部DNA含量和Olive尾矩显著升高. [结论]温室土壤中有机提取物可以诱使小鼠发生染色体和DNA损伤.     

酪酪肽对全肠内营养支持小鼠残留小肠代偿的影响

目的:通过建立广泛小肠切除(mSBR)的酪酪肽(PYY)基因敲除(Pyy-/-)小鼠模型,研究早期在TEN支持下PYY对残留小肠的代偿作用.方法:将30只Pyy-/-小鼠分为三组,每组10只.假手术(Sham)组仅横断小肠但不切除小肠;广泛小肠切除(mSBR)组切除50%小肠,保留近段空肠约1cm,远段回肠9ca;广泛小肠切除加PYY(mSBR-PYY)组切除50%小肠,皮内注射PYY1～36.所有小鼠术后2～7d均接受TEN.观察各组小鼠术后回肠黏膜的DNA和蛋白质含量、绒毛高度和隐窝深度、回肠隐窝细胞的增殖指数和绒毛上皮细胞的凋亡指数.结果:mSBR组小鼠同肠黏膜的DNA和蛋白质含量、绒毛高度、隐窝深度、回肠隐窝细胞的增殖指数和绒毛上皮细胞的凋亡指数,显著高于Sham组.mSBR-PYY组小鼠回肠黏膜的DNA和蛋白质含量、绒毛高度和隐窝深度,显著高于mSBR组;回肠隐窝细胞的增殖指数显著高于mSBR组;回肠绒毛上皮细胞的凋亡指数显著低于mSBR组.结论:在早期TEN支持下,PYY不仅能促进mSBR小鼠肠黏膜细胞的增殖,而且还能抑制其凋亡,在残留小肠的代偿中起重要作用.     

茶树菇水煎液对环磷酰胺诱发小鼠基因突变的保护作用

目的 研究茶树菇水煎液对环磷酰胺诱发KM小鼠突变的保护作用.方法 用改进的小鼠骨髓细胞微核实验和小鼠精子畸形实验方法,研究茶树菇水煎液对环磷酰胺诱发小鼠骨髓细胞微核和精子畸形的保护作用.结果 给40 mg/kg环磷酰胺后,茶树菇水煎液低、中、高剂量组及阳性对照组的微核率、精子畸形率均比阴性对照组显著升高(P＜0.01),茶树菇水煎液高剂量组的微核率18.2‰,显著低于阳性对照组微核率25.8‰(P＜0.01),茶树菇水煎液高剂量组的精子畸形率58.7‰,显著低于阳性对照组精子畸形率76.5‰(P ＜0.01).结论 茶树菇水煎液对环磷酰胺诱发小鼠骨髓细胞微核和精子畸形有保护作用.     

猪苓水溶性提取物预防镉诱发遗传式损伤研究

采用活体小鼠骨髓嗜多染红细胞微核试验方法，探讨中药猪苓水溶性提取物对镉诱发遗传损伤的预防作用．结果表明，镉可明显增高小鼠骨髓细胞微核率，在镉作用小鼠前，给予猪苓水溶性提取物．可明显降低镉诱发的遗传损伤．但对典型诱变剂环磷酰胺诱发的微核率无显著降低作用．     

绿茶提取物与维生素C和番茄红素的协同抗氧化作用

目的研究绿茶提取物联合维生素C和番茄红素对D-半乳糖致氧化损伤模型小鼠体内抗氧化活性的影响。方法 72只小鼠按体重随机抽取12只作为空白对照组,其余用D-半乳糖1.0 g/kg腹腔注射造模,6周后按照丙二醛(MDA)水平随机分为:模型对照组、绿茶提取物组和低、中、高3个剂量绿茶提取物+维生素C+番茄红素混合受试物组。模型对照组蒸馏水灌胃,绿茶提取物组0.87 g/kg单一绿茶提取物灌胃,低、中、高剂量混合受试物组分别按0.15、0.29、0.87 g/kg混合物灌胃。4周后用分光光度法测血清与肝脏内MDA含量、超氧化物歧化酶(SOD)活性、还原型谷胱甘肽(GSH)含量、谷胱甘肽过氧化物酶(GSH-Px)活性、蛋白质羰基含量。结果与氧化损伤模型对照组相比,高剂量混合物组、绿茶提取物组均能增高小鼠血清和肝组织内GSH-Px、SOD活性,降低蛋白质羰基、MDA含量(P<0.01或P<0.05);与绿茶提取物组比较,高剂量混合物组GSH-Px、SOD活性增高,MDA、蛋白质羰基含量降低(P<0.01或P<0.05)。结论绿茶提取物联合维生素C和番茄红素比单一使用绿茶提取物抗氧化效果更好,三者表现出良好的协同抗氧化能力。     

螺旋藻对二甲肼诱导大肠变性隐窝的抑制作用

本研究应用特异性癌致癌物１，２－二甲肼（ＤＭＨ）短期一次注射和长期多次注射分别诱导ＮＩＨ小鼠和ＳＤ大鼠肠癌前期病变一变性隐窝，并观察螺旋藻粉剂，猪－１３２，维生素Ｅ在ＤＭＨ诱导变性隐窝中的保护作用。研究结果显示：无论短期一次注射还是长期多次注射ＤＭＨ，均诱导出大肠变性隐窝。短期一次注射诱导的变性隐窝数量少，以散在分布为主，较少形成变性隐变窝病灶。螺旋藻粉剂，锗－１３２，维生素Ｅ均对变性隐窝的形成产     

儿茶素抑制二甲基肼诱发小鼠大肠癌的实验研究

昆明种小鼠随机分成７组，１～５组小鼠皮下注射二甲基肼（１，２－Ｄｉｍｅｔｈｙｌｈｙｄｒａｚｉｎｅ，ＤＭＨ），剂量２０ｍｇ／ｋｇｂｗ，每周一次，连续２０周。第２～５组于注射前一周开始灌胃儿茶素，每鼠每日分别为１ｍｇ、２ｍｇ、４ｍｇ、没食子酰表没食子儿茶素［（－）－Ｅｐｉｇａｌｌｏ－ｃａｔｅｃｈｉｎｇａｌｌａｔｅ］２ｍｇ，第６组给儿茶素３ｍｇ作为对照组，每周连续５次至２３周。第７组为溶剂对照组。２７周处死小鼠，结果显示：两组对照组小鼠未发现肿瘤。ＤＭＨ组大肠癌发生率为８０％，与２～５组比较明显升高（Ｐ＜０．００１），结果提示：（１）不同剂量的儿茶素都具有防癌作用，其机理可能与诱导ＳＯＤ等抗氧化剂的活性消除有害自由基有关；（２）其抑癌有效成分可能是多种儿茶素协同作用的结果；（３）儿茶素对个鼠无毒性作用。     

Effects of Green Tea and High-Fat Diet on Arachidonic Acid Metabolism and Aberrant Crypt Foci Formation in an Azoxymethane-Induced Colon Carcinogenesis Mouse Model

Excessive fat consumption is a risk factor for colon carcinogenesis, and green tea consumption may reduce the risk of colon and other cancers. The current study was designed to investigate the effects of green tea and a high-fat diet on arachidonic acid metabolism and aberrant crypt foci formation in an azoxymethane (AOM)-induced colon carcinogenesis mouse model. We also determined whether green tea consumption altered the size of regional fat pads. CF-1 female mice were maintained on either a high-fat (20% corn oil) or a low-fat (5% corn oil) diet. AOMwas given subcutaneous at a dose of 7.5 mg/kg body weight at 6 wk and then a dose of 10 mg/kg at 7 wk of age. Two weeks after the second AOM injection, 0.6% green tea (6 mg tea solids/ml) was given as the drinking fluid and continued for 10 wk until the experiment was terminated. In the AOM-treated mice not receiving green tea, the high-fat diet significantly enhanced colonic levels of 5-lipoxygenase, leukotriene A4 hydrolase, and leukotriene B4, but it did not significantly alter prostaglandin E2 levels and aberrant crypt foci formation. In AOM-treated mice on the high-fat diet, green tea significantly decreased colonic levels of cytosolic phospholipase A2, 5-lipoxygenase, and leukotriene B4; green tea treatment also decreased the number of aberrant crypt foci (P < 0.05). The weights of parametrial and retroperitoneal fat pads were increased by the high-fat diet and decreased by green tea treatment. The current results indicate that green tea consumption and dietary fat modulate 5-lipoxygenase-dependent pathway of arachidonic acid metabolism during AOM-induced colon carcinogenesis. Green tea inhibits ACF formation in mice on a high corn oil diet, suggesting its possible inhibitory effect on colon carcinogenesis in populations such as those in Western countries that consume high amounts of fat.     

Effects of green tea and high-fat diet on arachidonic acid metabolism and aberrant crypt foci formation in an azoxymethane-induced colon carcinogenesis mouse model

Excessive fat consumption is a risk factor for colon carcinogenesis, and green tea consumption may reduce the risk of colon and other cancers. The current study was designed to investigate the effects of green tea and a high-fat diet on arachidonic acid metabolism and aberrant crypt foci formation in an azoxymethane (AOM)-induced colon carcinogenesis mouse model. We also determined whether green tea consumption altered the size of regional fat pads. CF-1 female mice were maintained on either a high-fat (20% corn oil) or a low-fat (5% corn oil) diet. AOM was given subcutaneous at a dose of 7.5 mg/kg body weight at 6 wk and then a dose of 10 mg/kg at 7 wk of age. Two weeks after the second AOM injection, 0.6% green tea (6 mg tea solids/ml) was given as the drinking fluid and continued for 10 wk until the experiment was terminated. In the AOM-treated mice not receiving green tea, the high-fat diet significantly enhanced colonic levels of 5-lipoxygenase, leukotriene A4 hydrolase, and leukotriene B4, but it did not significantly alter prostaglandin E2 levels and aberrant crypt foci formation. In AOM-treated mice on the high-fat diet, green tea significantly decreased colonic levels of cytosolic phospholipase A2, 5-lipoxygenase, and leukotriene B4; green tea treatment also decreased the number of aberrant crypt foci (P < 0.05). The weights of parametrial and retroperitoneal fat pads were increased by the high-fat diet and decreased by green tea treatment. The current results indicate that green tea consumption and dietary fat modulate 5-lipoxygenase-dependent pathway of arachidonic acid metabolism during AOM-induced colon carcinogenesis. Green tea inhibits ACF formation in mice on a high corn oil diet, suggesting its possible inhibitory effect on colon carcinogenesis in populations such as those in Western countries that consume high amounts of fat.     

酸牛乳抑制1,2-二甲基肼诱发小鼠大肠癌的实验研究

106只小鼠随机分成5组,每组18至23只。1～3组小鼠皮下注射1,2-二甲基肼(DMH),剂量20mg/kg体重,每周一次,连续20周。实验结束前,动物分别自由饮用自来水(第一组),水加嗜酸乳酸杆菌酸牛乳(第二组)及水加牛乳(第三组)。第4组和第5组为对照组,动物分别皮下注射1mM EDTA和蒸馏水。 27周诱癌期后,对照组小鼠未发生肿瘤。DMH处理动物中,第2组的结肠癌发生率为44.4％,比第1组(80％)和第3组(100％)明显降低(P<0.05)。此外,实验期间第2组动物的存活率(100％) 比第1组(80％)和第3组(74％)都高。结论是喂饲嗜酸乳酸杆菌(Shahani株)制备的酸牛乳能显著降低DMH诱发的小鼠癌肿和死亡率,而单纯牛乳则能增加。本研究的资料提示,食物中添加活嗜酸乳酸杆菌可能有助于预防结肠癌。     

Dietary supplementation of resveratrol suppresses colonic tumour incidence in 1,2-dimethylhydrazine-treated rats by modulating biotransforming enzymes and aberrant crypt foci development

Diet-induced changes in the activities of bacterial enzymes are known to play a role in colon cancer development. Resveratrol has been implicated as a protective agent in carcinogenesis. In the present study, the effect of resveratrol on the activities of faecal and colonic biotransforming enzymes such as beta-glucuronidase, beta-glucosidase, beta-galactosidase, mucinase, nitroreductase and faecal sulfatase activity was assessed. The total number of aberrant crypt foci and their distribution in the proximal, medial and distal colon were observed in 1,2-dimethylhydrazine (DMH)-induced rats (group 3) and other treatment groups (groups 4-6). DMH (0.02 g/kg body weight) was given subcutaneously once a week for 15 consecutive weeks, and the experiment was terminated at 30 weeks. DMH-treated rats showed elevated levels of cancer-associated bacterial enzyme activities, whereas on resveratrol supplementation in three different regimens, rats showed lowered activities. Resveratrol supplementation throughout the experimental period (group 6) exerted a more pronounced effect (P < 0.01) by modulating the development of aberrant crypt foci and the activities of bacterial enzymes than did the other treatment regimens (groups 4 and 5). Thus, the present results demonstrate the inhibitory effect of resveratrol on DMH-induced colon carcinogenesis in rats.     

The protective role of Lychnophora ericoides Mart. (Brazilian arnica) in 1,2-dimethylhydrazine-induced experimental colon carcinogenesis

Aberrant crypt foci (ACF) and colon rectal mucosal epithelial cell proliferation have been shown to be increased in patients with colon cancer and have been largely used for early detection of factors that influence colorectal carcinogenesis in rats. Fifty male Wistar rats were randomly divided into 5 groups. The groups G1 to G4 were given 4 injections of the carcinogen 1,2-dimethylhydrazine (DMH). The G2 group received Lychnophora ericoides (LE) extracts for 6 wk. The groups G3 and G4 received LE for 4 wk and 2 wk, respectively, at the postinitiation and initiation phases of colonic carcinogenesis. The group G5 was the control. Forty-two days after the first injections of DMH for the neoplasic induction, we observed a statistically significant decrease in the number of aberrant crypt foci (ACF) and an attenuation of the increase in cell proliferation induced by DMH in all the LE-treated groups. Thus, we concluded that Lychnophora ericoides extracts were effective against the development of cancer. These data suggest that LE has a protective influence on the process of colon carcinogenesis, suppressing both the initiation and the promotion of colonic carcinogenesis.     

The Protective Role of Lychnophora ericoides Mart. (Brazilian Arnica) in 1,2-Dimethylhydrazine-Induced Experimental Colon Carcinogenesis

Aberrant crypt foci (ACF) and colon rectal mucosal epithelial cell proliferation have been shown to be increased in patients with colon cancer and have been largely used for early detection of factors that influence colorectal carcinogenesis in rats. Fifty male Wistar rats were randomly divided into 5 groups. The groups G1 to G4 were given 4 injections of the carcinogen 1,2-dimethylhydrazine (DMH). The G2 group received Lychnophora ericoides (LE) extracts for 6 wk. The groups G3 and G4 received LE for 4 wk and 2 wk, respectively, at the postinitiation and initiation phases of colonic carcinogenesis. The group G5 was the control. Forty-two days after the first injections of DMH for the neoplasic induction, we observed a statistically significant decrease in the number of aberrant crypt foci (ACF) and an attenuation of the increase in cell proliferation induced by DMH in all the LE-treated groups. Thus, we concluded that Lychnophora ericoides extracts were effective against the development of cancer. These data suggest that LE has a protective influence on the process of colon carcinogenesis, suppressing both the initiation and the promotion of colonic carcinogenesis.     

p38 MAPK/AP-1信号通路在1，2-二氯乙烷中毒性脑水肿形成中对iNOS表达的上调作用

目的探究p38 MAPK/AP-1信号通路在小鼠1?2-二氯乙烷(1?2-DCE)中毒性脑水肿形成过程中对诱导型一氧化氮合酶(iNOS)表达的作用及其对脑水肿的影响。方法选取40只雌性昆明种小鼠随机分为对照组、染毒组、低剂量以及高剂量p38抑制剂组。染毒小鼠于染毒柜中1.2 mg/L 1?2-二氯乙烷染毒3.5 h/d,连续染毒3 d,低、高剂量抑制剂组小鼠于染毒前1 h腹腔注射200μl 3.75、15 mg/kg的p38 MAPK抑制剂(SB202190)。染毒结束次日取材,测定各组小鼠脑含水量及HE病理观察脑水肿,Western Blot检测各组小鼠脑组织中磷酸化p38、激活蛋白1(AP-1)两个亚基c-fos、c-jun的磷酸化形式表达水平以及iNOS的蛋白表达,Real-Time RT-PCR检测iNOS mRNA表达水平。结果单纯染毒组的小鼠出现抱爪现象,SB202190干预能够明显改善1?2-DCE中毒小鼠的抱爪症状。染毒组小鼠脑组织含水量与对照组小鼠相比明显增加,SB202190干预能够有效缓解小鼠出现脑水肿。单纯染毒组小鼠脑组织中p-p38蛋白、磷酸化c-jun和c-fos表达水平明显上调,iNOS蛋白和mRNA表达水平也显著增加,而SB202190能够显著降低iNOS、磷酸化c-jun和c-fos的表达水平。结论小鼠脑组织iNOS mRNA和蛋白表达水平在1?2-DCE中毒性脑水肿形成过程中显著上调。p38 MAPK/AP-1信号通路参与iNOS表达增多的调控过程。     

Inhibition by White Tea of 2-Amino-1-Methyl-6-Phenylimidazo[4,5-b]Pyridine-Induced Colonic Aberrant Crypts in the F344 Rat

There is growing interest in the potential health benefits of tea, including the anticarcinogenic properties. We report here that white tea, the least processed form of tea, is a potent inhibitor of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP)-induced colonic aberrant crypts in the rat. Male Fischer 344 rats were treated for 8 wk with white tea (2% wt/vol) or drinking water alone, and on alternating days in experimental Weeks 3 and 4 the animals were given PhIP (150 mg/kg body wt po) or vehicle alone. At the end of the study there were 5.65 ± 0.81 and 1.31 ± 0.27 (SD) aberrant crypt foci per colon in groups given PhIP and PhIP + white tea, respectively (n = 12, P ? 0.05). No changes were detected in N-acetyltransferase or arylsulfotransferase activities compared with controls, but there was marked induction of ethoxyresorufin O-deethylase, methoxyresorufin O-demethylase, and UDP-glucuronosyltransferase after treatment with white tea. Western blot revealed corresponding increases in cytochrome P-450 1A1 and 1A2 proteins. Enzyme assays and Western blot also revealed induction of glutathione S-transferase by white tea. There was less parent compound and 4?-hydroxy-PhIP but more PhIP-4?-O-glucuronide and PhIP-4?-O-sulfate in the urine from rats given PhIP + white tea than in urine from animals given carcinogen + drinking water. The results indicate that white tea inhibits PhIP-induced aberrant crypt foci by altering the expression of carcinogen-metabolizing enzymes, such that there is increased ring hydroxylation at the 4? position coupled with enhanced phase 2 conjugation.     

Inhibition by white tea of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine-induced colonic aberrant crypts in the F344 rat

There is growing interest in the potential health benefits of tea, including the anticarcinogenic properties. We report here that white tea, the least processed form of tea, is a potent inhibitor of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP)-induced colonic aberrant crypts in the rat. Male Fischer 344 rats were treated for 8 wk with white tea (2% wt/vol) or drinking water alone, and on alternating days in experimental Weeks 3 and 4 the animals were given PhIP (150 mg/kg body wt p.o.) or vehicle alone. At the end of the study there were 5.65 +/- 0.81 and 1.31 +/- 0.27 (SD) aberrant crypt foci per colon in groups given PhIP and PhIP + white tea, respectively (n = 12, P < 0.05). No changes were detected in N-acetyltransferase or arylsulfotransferase activities compared with controls, but there was marked induction of ethoxyresorufin O-deethylase, methoxyresorufin O-demethylase, and UDP-glucuronosyltransferase after treatment with white tea. Western blot revealed corresponding increases in cytochrome P-450 1A1 and 1A2 proteins. Enzyme assays and Western blot also revealed induction of glutathione S-transferase by white tea. There was less parent compound and 4'-hydroxy-PhIP but more PhIP-4'-O-glucuronide and PhIP-4'-O-sulfate in the urine from rats given PhIP + white tea than in urine from animals given carcinogen + drinking water. The results indicate that white tea inhibits PhIP-induced aberrant crypt foci by altering the expression of carcinogen-metabolizing enzymes, such that there is increased ring hydroxylation at the 4' position coupled with enhanced phase 2 conjugation.