鳖甲育肝颗粒对乙醇性肝纤维化大鼠的影响*

目的:探讨鳖甲育肝颗粒对乙醇性肝纤维化大鼠的防治作用。方法:将SD大鼠随机分为空白对照组、模型对照组、鳖甲育肝颗粒对照组、秋水仙碱组、鳖甲育肝颗粒低剂量组和鳖甲育肝颗粒高剂量组(n=8),采用梯度乙醇灌胃法复制肝纤维化动物模型,即除了空白对照组及鳖甲育肝颗粒对照组灌胃等量纯净水外,其余各组大鼠第1～4周灌胃5 g/(kg·d)乙醇,第5～8周灌胃7 g/(kg·d)乙醇,第9～12周灌胃9 g/(kg·d)乙醇,第13～24周灌胃9.5 g/(kg·d)乙醇,其中乙醇剂量计算采用下列公式:乙醇剂量(g) = 无水乙醇体积(ml)×预配乙醇浓度(%)×0.8(g/ml),同时每天灌胃相应的药物:鳖甲育肝颗粒对照组灌胃鳖甲育肝颗粒5.55 g/kg、秋水仙碱组灌胃秋水仙碱0.1 mg/kg、鳖甲育肝颗粒低剂量组灌胃鳖甲育肝颗粒1.85 g/kg、鳖甲育肝颗粒高剂量组灌胃鳖甲育肝颗粒5.55 g/kg,空白对照组及模型对照组灌胃等量纯净水。实验第169日观测鳖甲育肝颗粒对大鼠肝脏脏器宏观变化、肝组织含水量及其纤维化病理变化、肝组织羟脯氨酸(Hyp)含量及α-平滑肌肌动蛋白(α-SMA)、CREB表达水平的影响。结果:1.85、5.55 g/kg鳖甲育肝颗粒能明显改善乙醇性肝纤维化大鼠肝脏脏器宏观变化及肝组织纤维化病理变化,降低肝组织含水量及Hyp的含量,下调α-SMA、CREB表达水平。结论:鳖甲育肝颗粒具有明显的抑制乙醇性肝纤维化的作用,而下调CREB是其抗肝纤维化的作用机制之一。     

羊骨胶原肽钙螯合物对去卵巢大鼠肾组织病变的改善作用

目的 探究羊骨胶原肽钙螯合物(collagen peptide chelated calcium,CPCC)对雌激素缺乏大鼠肾的保护作用及相关机制.方法 摘除大鼠双侧卵巢,CPCC高(CPCC-H)和低(CPCC-L)剂量组的灌胃剂量分别为5 g/(kg·d)和1 g/(kg·d),假手术组和模型组灌胃等体积蒸馏水.8...     

过量人参皂苷对小鼠脑组织谷氨酸代谢的影响

目的:探讨过量人参皂苷对小鼠脑组织中谷氨酸代谢的影响。方法:常规饲养昆明小鼠,按照最终浓度低(8 mg/kg)、中(40mg/kg)、高(200 mg/kg)剂量连续灌胃人参皂苷24天,记录小鼠体重变化。第25天颈脱臼处死小鼠,取出全脑匀浆后测定谷氨酸水平,谷氨酰胺酶活力。结果:各实验组与对照组相比,体重明显下降;低、中、高实验组谷氨酸水平分别高与对照组13.66%、21.67%、39.83%,其中中剂量组和高剂量组显著高于空白组(P0.05);谷氨酰胺酶活力较对照组分别增高2.06%、2.91%、10.11%,高剂量与空白组差异显著,有统计学意义(P0.05)。结论:高剂量人参皂苷能使神经系统兴奋,可能与增高谷氨酰胺酶活力、从而提高脑组织中谷氨酸含量有关。     

加味四妙散对尿酸钠诱导急性痛风性关节炎大鼠的疗效机制研究

目的:研究急性痛风性关节炎大鼠应用加味四妙散的疗效,并研究其作用机制。方法:将60只雄性Wistar大鼠按照随机数字法随机分为5组,每组各12只,分组情况为:空白对照组、模型对照组、低剂量组(8.875 g/kg·d)、中剂量组(17.750 g/kg·d)及高剂量组(35.500 g/kg·d)。模型建立后每天灌胃治疗,持续3 d。计算并比较各组大鼠造模后4 h、24 h、48 h、72 h时踝关节的肿胀度。检测并比较各组大鼠血清白介素-1β(IL-1β)、肿瘤坏死因子-α(TNF-α)及尿酸(UA)水平。结果:(1)造模24h后,模型对照组大鼠关节肿胀度达到峰值,并且明显大于空白对照组,具有显著性差异(P0.05);模型对照组大鼠关节肿胀度明显大于各剂量组,同时高剂量组大鼠关节肿胀度明显小于中剂量组和低剂量组,均具有显著性差异(P0.05)。造模48 h后,各组大鼠关节肿胀度均继续下降,且各剂量组大鼠关节肿胀度明显小于模型对照组,均具有显著性差异(P0.05)。造模72 h后,各治疗组大鼠关节肿胀度均明显小于模型对照组,同时高剂量组大鼠关节肿胀度明显小于中剂量组和低剂量组,均具有显著性差异(P0.05)。(2)与空白对照组比较,模型对照组大鼠血清IL-1β、TNF-α及UA水平均明显偏高,具有显著性差异(P0.05);与模型对照组、低剂量组比较,中剂量组和高剂量组大鼠血清IL-1β、TNF-α及UA水平均明显偏低,具有显著性差异(P0.05)。结论:加味四妙散35.500 g/kg剂量能明显改善急性痛风性关节炎大鼠症状,减轻踝关节肿胀度,降低血清IL-1β、TNF-α及UA水平,对急性痛风性关节炎大鼠具有治疗作用。     

基于OPG/RANK/RANKL信号通路探讨铁筷子对CIA大鼠骨破坏的防护作用

目的 探讨铁筷子对胶原诱导性关节炎(collagen induced arthritis, CIA)模型大鼠的抗炎作用及对OPG/RANK/RANKL信号通路的影响。方法 雌性Wistar大鼠60只分为：正常组、模型组、阳性药物组(甲氨蝶呤,MTX)、低剂量组、中剂量组和高剂量组。采用胶原抗体诱导法于大鼠尾根部注射牛Ⅱ型胶原蛋白建立CIA大鼠模型,模型建立成功后进行灌胃给药,正常组：给予10 mL/(kg·d)生理盐水;模型组：给予10 mL/(kg·d)生理盐水;阳性药物组每次给予2.0 mL/(kg·d) MTX,每周3次;铁筷子低、中、高剂量组每次分别给予0.25 g/(kg·d)、 0.5 g/(kg·d)、1.0 g/(kg·d);连续灌胃治疗25 d。通过记录大鼠体重;观察大鼠足肿胀程度;大鼠踝关节炎指数评分;micro-CT观察踝关节骨组织病理改变;苏木素-伊红(HE)染色对大鼠踝关节骨组织和滑膜病理变化;抗酒石酸酸性磷酸酶(TRAP)染色法检测观察破骨细胞数量的改变;PCR检测骨保护素(OPG)、核因子-κB受体激活剂(RANK)、RANK配体(RANKL)、肿瘤坏死因...     

黄连浸出液对脑缺血大鼠海马区BDNF mRNA表达的影响

为了探究黄连浸出液对局灶性脑缺血再灌注大鼠海马区脑源性神经营养因子(BDNF)mRNA表达的影响,本研究随机将50只雄性SD大鼠(240±20) g分为假手术组、模型组、黄连浸出液低剂量(2.5 g/kg)、中剂量(5.0 g/kg)和高剂量(10.0 g/kg)治疗组,采用线栓法建立大鼠局灶性脑缺血(MCAO)模型,假手术组不予线栓处理,术后对大鼠进行神经功能评分。对各治疗组给予灌胃治疗,按照人和大鼠等效剂量关系换算,每只大鼠1d灌胃两次,每次2.5 mL,连续灌胃3d。模型组、假手术组用等量生理盐水灌胃。应用RT-PCR测定了黄连浸出液对局灶性脑缺血再灌注大鼠海马区BDNF表达的影响。与假手术组(BDNF mRNA相对表达量为(0.386±0.011)比较),模型组大鼠海马区BDNF mRNA表达显著增加,相对表达量为(0.458±0.029),差异具有统计学意义(p0.05);与模型组比较,黄连中剂量和高剂量治疗组BDNF mRNA的表达均显著增加,相对表达量分别为(0.622±0.040)和(0.518±0.033),差异均有统计学意义(p0.05);与黄连高剂量组相比,中剂量治疗组差异更为显著(p0.05)。本研究表明,黄连浸出液可促进脑缺血再灌注损伤大鼠海马区BDNF mRNA的表达,改善脑缺血再灌注损伤大鼠的神经功能,保护神经元,黄连浸出液中剂量(5.0 g/kg)作用更为明显。     

黄连素对糖尿病大鼠胰岛素抵抗的治疗作用*

目的:探讨黄连素对链脲佐菌素所致糖尿病大鼠胰岛素抵抗的治疗作用。方法:采用链脲佐菌素腹腔注射的方式建立大鼠糖尿病模型,将实验大鼠分为5组:分别为模型组、黄连素低(100 mg/kg)、黄连素中(200 mg/kg)、黄连素高(300 mg/kg)剂量组和阳性对照组(二甲双胍:50 mg/kg),每组10只。另取10只正常大鼠作为正常组。黄连素低、中、高剂量组小鼠每天分别灌胃100、200和300 mg/kg黄连素;对照组每天灌胃二甲双胍50 mg/kg;正常组和模型组每天给予相同体积的生理盐水进行灌胃;1次/天,连续灌胃4周。通过测定大鼠血FBG、果糖胺水平,OGTT实验,胰岛素(FINS)水平,并计算大鼠胰岛素抵抗指数(HOMA-IR)来评价黄连素对糖尿病大鼠胰岛素抵抗作用。结果:与正常组相比,给药前模型组大鼠静脉血FBG含量显著升高(P＜0.05);与模型组比较,给药2周及以后给药4周后阳性对照组、黄连素中剂量组和高剂量组大鼠静脉血FBG含量均显著下降(P＜0.05);给药4周后,阳性对照组、黄连素低、中、高剂量组OGTT实验结果显示在不同时间节点的血糖值均显著低于模型组(P＜ 0.05),阳性对照组、黄连素低、中、高剂量组FBG、果糖胺水平和HOMA-IR指标均低于模型组(P＜0.05);而胰岛素水平水平较模型组显著升高(P＜0.05)。结论:黄连素可明显降低大鼠的空腹血糖、果糖胺含量,提高胰岛素含量,对链脲佐菌素所致糖尿病大鼠的胰岛素抵抗有明显治疗作用。且一定范围内,黄连素剂量越高,对糖尿病大鼠胰岛素抵抗作用越明显。     

清肺化痰逐瘀汤治疗慢性阻塞性肺疾病模型大鼠的疗效及机制研究

目的:探讨清肺化痰逐瘀汤治疗慢性阻塞性肺疾病(COPD)大鼠的疗效及作用机制。方法:将60只SD大鼠按照随机数字表法分为空白对照组、模型对照组、低剂量组、中剂量组及高剂量组,每组各12只。空白对照组大鼠每天以生理盐水灌胃,将其他四组大鼠建立COPD模型,模型建立后,模型对照组每天以生理盐水灌胃,低剂量组、中剂量组、高剂量组分别以2 m L/100 g·d、3 m L/100 g·d、4 m L/100 g·d的清肺化痰逐瘀汤灌胃,各组均持续14d。比较各组大鼠症状改善情况、动脉血中氧分压(PO2)、二氧化碳分压(PCO2)以及血清白介素-1β(IL-1β)、白介素-8(IL-8)、肿瘤坏死因子-α(TNF-α)、白三烯B4(LTB4)及超氧化物歧化酶(SOD)水平。结果:低剂量组、中剂量组、高剂量组大鼠饮食、精神、毛发等状况均有所改善,且高剂量组大鼠症状缓解最为明显。模型对照组、低剂量组、中剂量组、高剂量组大鼠血清IL-1β、IL-8、TNF-α、LTB4及PCO2水平均明显高于空白对照组,血清SOD及PO2水平明显低于空白对照组(P<0.05);且模型对照组、低剂量组、中剂量组、高剂量组大鼠血清IL-1β、IL-8、TNF-α、LTB4及PCO2水平逐渐降低,血清SOD及PO2水平逐渐升高(P<0.05)。结论:清肺化痰逐瘀汤能明显改善COPD大鼠症状和动脉血气,疗效确切,且高剂量清肺化痰逐瘀汤改善作用最明显,其可能机制是通过降低大鼠炎症因子及LTB4水平,提高SOD水平,从而抑制其机体炎症反应,增强抗氧化能力。     

大豆卵磷脂降血脂功能的动物实验研究

目的研究大豆卵磷脂的降血脂作用。方法雄性Wistar大鼠喂普通饲料7d后,根据TC水平随机分成5组,每组10只,分别为大豆卵磷脂高、中、低三个剂量组,模型对照组和空白对照组。以灌胃方式(10mL/kg)给予受试物,除空白对照组外,各组均喂高脂饲料,连续喂养30d后,称重、取大鼠眼血测定各项血脂指标。结果 1.2g/(kg·BW)、2.4g/(kg·BW)剂量组的大豆卵磷脂能使高胆固醇血症大鼠血清TC降低,与模型对照组比较差异有统计学意义(P0.05)。结论大豆卵磷脂对大鼠具有降血脂作用。     

超滤得到的海蜇酶解产物的降血脂功能评价

目的:探讨超滤对于海蜇酶解产物降血脂功能的提高作用。方法:海蜇通过中性蛋白酶酶解后,将超滤过的酶解产物和未超滤的酶解产物分别按照高、中、低三个剂量组喂食高血脂症大鼠模型42d,测定各组血脂水平并进行对照分析。结论:未超滤组的高、中剂量组和超滤组高中低剂量组喂食42d后均观察到大鼠血清总胆固醇(TC)、甘油三酯(TG)的降低,其中未超滤中剂量组(灌胃剂量5 mg/kg.BW)血清总胆固醇(TC)值为2.45±0.28mmol/L,超滤低剂量组(灌胃剂量0.3mg/kg.BW)血清总胆固醇(TC)值为2.61±0.33mmol/L,均明显低于高脂模型对照组(3.38±0.22 mmol/L),未超滤低剂量组(灌胃剂量3mg/kg.BW)血清总胆固醇(TC)值为2.82±0.38mmol/L,相对于高脂模型对照组(3.38±0.22 mmol/L)无显著差异;未超滤中剂量组(灌胃剂量5 mg/kg.BW)甘油三酯(TG)值为0.90±0.21mmol/L,超滤低剂量组(灌胃剂量0.3mg/kg.BW)甘油三酯(TG)值为0.93±0.14 mmol/L,均明显低于高脂模型对照组(1.21±0.20 mmol/L),未超滤低剂量组(灌胃剂量3mg/kg.BW)甘油三酯(TG)值为1.18±0.12mmol/L,相对于高脂模型对照组(1.21±0.20 mmol/L)无显著差异。结论:海蜇多肽的酶解产物具有降血脂功能,超滤能够有效提高海蜇酶解产物的降血脂活性。     

阿霉素注射剂量对肾病综合征大鼠脂蛋白脂酶和卵磷脂胆固醇酰基转移酶水平的影响

摘要 目的：探讨阿霉素注射剂量对肾病综合征（nehpmtic syndrome,NS）大鼠脂蛋白脂酶和卵磷脂胆固醇酰基转移酶（Leci-thin cholesterol acyltransferase,LCAT）水平的影响。方法：64只SD大鼠随机平分为四组-对照组、小剂量阿霉素组、中剂量阿霉素组与高剂量阿霉素组,四组大鼠经尾静脉一次性注射阿霉素0 mg/kg、2 mg/kg、4 mg/kg、8 mg/kg,检测造模后不同时间点大鼠肾脏脂蛋白脂酶和卵磷脂胆固醇酰基转移酶水平变化情况。结果：小剂量阿霉素组、中剂量阿霉素组与高剂量阿霉素组造模后7 d、14 d、21 d的体重与每日采食量、血肌酐与尿素氮都低于对照组（P<0.05）,24 h尿蛋白高于对照组（P<0.05）,且存在剂量依赖性,三组间对比差异有统计学意义（P<0.05）。小剂量阿霉素组、中剂量阿霉素组与高剂量阿霉素组造模后21 d、28 d的肾脏脂蛋白脂酶和卵磷脂胆固醇酰基转移酶相对表达水平低于对照组（P<0.05）,且存在剂量依赖性,三组间对比差异有统计学意义（P<0.05）。结论：小剂量阿霉素可抑制大鼠肾脏脂蛋白脂酶和卵磷脂胆固醇酰基转移酶的表达,能快速有效建立肾病综合征大鼠模型,具有很好的模拟造模效果。     

Magnesium Supplementation did not Affect the Increasing Bone Zinc Concentration in Rats Given Excess Calcium as Carbonate

We investigated the effect of magnesium supplementation on zinc distribution in rats given excess calcium as carbonate. Rats were given a control diet (5 g/kg calcium and 0.5 g/kg magnesium), a high calcium diet (HC, 25 g/kg calcium and 0.5 g/kg magnesium) or the high calcium diet supplied with magnesium (HCM, 25 g/kg calcium and 2.5 g/kg magnesium) for 4 weeks. Calcium carbonate and magnesium oxide were used for increasing these mineral concentrations in diets. Although feed intake did not differ among the groups, the excess calcium suppressed feed efficiency, irrespective of dietary magnesium concentration. Femoral magnesium concentration was lower in the HC group than in the control and the HCM groups. Femoral zinc concentration was higher in the HC group and the HCM group than in the control group. The zinc concentration in the kidney was lower in the HC group and the HCM group than in the control group. The excess calcium did not affect zinc concentration in plasma and other tissues such as the liver, testis, and spleen, irrespective of dietary magnesium. These results suggest that the increasing bone zinc and the decreasing renal zinc do not result from magnesium insufficiency in rats given excess calcium as carbonate.     

The reproductive toxicity of yttrium nitrate in a two-generation study in Sprague-Dawley rats

ObjectiveTo evaluate the effects of yttrium nitrate on the development of the parent, offspring and third generation of Sprague-Dawley (SD) rats by using a two-generation reproductive toxicity test.MethodsThe SD rats were randomly divided into 0 mg/kg group, 10.0 mg/kg group, 30.0 mg/kg group and 90.0 mg/kg group according to the different doses of yttrium nitrate administration. The reproductive toxicity of parent, offspring and third generation SD rats were compared.ResultsThe weight gains of F1a female rats and F2a female rats in the low-dose groups were significantly lower than those of the control groups (p < 0.05), the weight gains of F1a male rats in the medium-dose and high-dose groups were significantly lower than those of the control groups (p < 0.05), and the weight gains of F2a male rats in the low-dose, medium-dose and high-dose groups were significantly lower than those of the control groups (p < 0.05). In F0 male rats, the absolute weight and relative weight of the liver in the low-dose, middle-dose, and high-dose groups were significantly lower than those of the control group (p < 0.05). In F1b male rats, the absolute and relative weights of the liver in the medium-dose and high-dose groups were significantly lower than those of the control group (p < 0.05). In F2b male rats, the absolute and relative weights of the liver and spleen of the medium-dose and high-dose groups were significantly lower than those of the control group (p < 0.05). In F2a female rats, the absolute weight and relative weight of oviduct in the high-dose group were significantly lower than those in the control group (p < 0.05). The absolute and relative weights of lung, spleen, brain and uterus of F2b female rats in the high-dose group were higher than those of the control group (p < 0.05). But the pathological test results showed no hepatotoxicity. There was no statistically significant difference in sperm count and sperm motility between male rats in the yttrium nitrate administration groups and the control group (p > 0.05). There was no significant correlation between F0, F1a, F1b, F2a, F2b SD rats' reproductive organ lesions and the dose of yttrium nitrate.ConclusionYttrium nitrate at a dose of 90 mg/kg has no reproductive toxicity to two generations of SD rats, but 30.0 mg/kg dose of yttrium nitrate is toxic to the liver weight of male two generations of SD rats, but no hepatotoxicity.     

海藻酸钙对骨质疏松症大鼠骨骼肌SDF-1含量和骨密度的影响

摘要 目的：探讨海藻酸钙对骨质疏松症大鼠骨骼肌基质细胞衍生因子-1（Stromal Cell-derived Factor-1,SDF-1）含量和骨密度的影响。方法：骨质疏松症大鼠（n=48）随机平分为三组-模型组、尼尔雌醇组与海藻酸钙组,在建模后1周后三组分别给予双蒸水、0.1 mg/100 g尼尔雌醇与37.5 mg/mL海藻酸钙/枸杞多糖凝胶微球水溶液灌胃治疗,1 次/d,检测大鼠骨骼肌SDF-1含量和骨密度变化情况。结果：（1）尼尔雌醇组与海藻酸钙组给药第4周与第8周的血清钙离子含量高于模型组（P<0.05）,磷离子含量低于模型组（P<0.05）,尼尔雌醇组与海藻酸钙组对比差异有统计学意义（P<0.05）;（2）尼尔雌醇组与海藻酸钙组给药第4周与第8周的骨骼肌SDF-1含量低于模型组（P<0.05）,海藻酸钙组低于尼尔雌醇组（P<0.05）;（3）尼尔雌醇组与海藻酸钙组给药第4周与第8周的腰椎和股骨骨密度高于模型组（P<0.05）,海藻酸钙组低于尼尔雌醇组（P<0.05）;（4）尼尔雌醇组与海藻酸钙组给药第4周与第8周的股骨最大载荷、最大应力高于模型组(P<0.05),海藻酸钙组高于尼尔雌醇组（P<0.05）;（5）海藻酸钙组造血细胞数量较多,骨皮质结构较完整,致密均匀粗壮,小梁数目明显增多,骨髓腔变小。结论：海藻酸钙在骨质疏松症大鼠的应用能抑制骨骼肌SDF-1的释放,有助于提高骨密度,改善骨生物力学指标,提高血清钙离子含量,降低磷离子含量。     

Ausscheidungen der Aminosäuren mit dem Harn und Kot von kolostomierten und nicht operierten Hennen — Beitrag zur Methode der Aminosäurenresorbierbarkeit

Veal calves aged 8 weeks were fed iso‐energetic amounts of milk replacers with either a low (7.1g of calcium/kg of air‐dry diet) or a high concentration of calcium (11.6g of calcium/kg of air‐dry diet) for a period of 10 weeks. The extra calcium was added in the form of calcium formiate. Final body weight of the two dietary groups was similar. Faeces were collected during the final week of the trial. The high calcium diet raised faecal dry matter output by 87% and faecal energy by 70%. The extra output of faecal dry matter was composed of 36% and 37% of crude fat and ash, respectively. The extra faecal energy output was for 75% in the form of crude fat. The high versus low calcium intake not only depressed apparent digestibility of total lipids but also that of crude protein, carbohydrates and ash. It is concluded that a high calcium intake by veal calves reduced energy availability without affecting body weight gain.     

Consumption of Calcium-Fortified Cereal Bars to Improve Dietary Calcium Intake of Healthy Women: Randomized Controlled Feasibility Study

Calcium is an important structural component of the skeletal system. Although an adequate intake of calcium helps to maintain bone health and reduce the risk of osteoporosis, many women do not meet recommended daily intakes of calcium. Previous interventions studies designed to increase dietary intake of women have utilized primarily dairy sources of calcium or supplements. However, lactose intolerance, milk protein allergies, or food preferences may lead many women to exclude important dairy sources of dietary calcium. Therefore, we undertook a 9 week randomized crossover design trial to examine the potential benefit of including a non-dairy source of calcium in the diet of women. Following a 3 week run-in baseline period, 35 healthy women > 18 years were randomized by crossover design into either Group I or Group II. Group I added 2 calcium-fortified cereal bars daily (total of 400 mg calcium/day) (intervention) to their usual diet and Group II continued their usual diet (control). At the end of 3 weeks, diets were switched for another 3 weeks. Intakes of calcium and energy were estimated from 3-day diet and supplemental diaries. Wilcoxon signed-rank tests were used for within group comparisons and Mann Whitney U tests were used for between group comparisons of calcium and energy intake. Dietary calcium was significantly higher during intervention (1071 mg/d) when participants consumed 2 calcium-fortified cereal bars daily than during the baseline (720 mg/d, P <0.0001) or control diets (775 mg/d, P = 0.0001) periods. Furthermore, the addition of 2 calcium-fortified cereal bars daily for the 3 week intervention did not significantly increase total energy intake or result in weight gain. In conclusion, consumption of calcium-fortified cereal bars significantly increased calcium intake of women. Further research examining the potential ability of fortified cereal bars to help maintain and improve bone health of women is warranted.

Trial Registration

ClinicalTrials.gov NCT01508689     

Metformin reduces the stimulatory effect of obesity on in vivo Walker-256 tumor development and increases the area of tumor necrosis

AimsThe objective of this study was to analyze the influence of obesity and insulin resistance on tumor development and, in turn, the effect of insulin sensitizing agents.Main methodsMale offspring of Wistar rats received monosodium glutamate (400 mg/kg) (obese) or saline (control) from the second to sixth day after birth. Sixteen-week-old control and obese rats received 5 × 10⁵ Walker-256 tumor cells, subcutaneously injected into the right flank. Some of the obese and control rats received concomitant treatment with metformin (300 mg/kg) by gavage. At the 18th week, obesity was characterized. The percentage of rats that developed tumors, the tumor relative weight and the percentage of cachexia incidence were analyzed. The tumor tissue was evaluated histologically by means of hematoxylin and eosin staining.Key findingsMetformin did not correct the insulin resistance in obese rats. The tumor development was significantly higher in the obese group, whereas metformin treatment reduced it. After pathological analysis, we observed that the tumor tissues were similar in all groups except for adipocytes, which were found in greater quantity in the obese and metformin-treated obese groups. The area of tumor necrosis was higher in the group treated with metformin when compared with the untreated one.SignificanceMetformin reduced Walker-256 tumor development but not cachexia in obese rats. The reduction occurred independently of the correction of insulin resistance. Metformin increased the area of necrosis in tumor tissues, which may have contributed to the reduced tumor development.     

Calcium intake and the outcome of short-term weight management

Experimental and epidemiological studies suggest that calcium intake is inversely related to weight gain. Calcium of dairy origin has been shown to be more effective in promoting weight loss. However, clinical studies yielded controversial results concerning the role of calcium intake in weight change. The aim of this study was to ascertain whether the addition of calcium can affect the outcome of 3-week weight management (WM) with a hypocaloric diet characterized by a decreased calcium intake. Overweight/ obese women (n=67; BMI 32.2+/-4.1 kg/m(2); age 49.1+/-12.1 years) underwent a 4-week comprehensive WM program. WM included a 7 MJ/day diet resulting in a stable weight during the first week and a 4.5 MJ/day diet with mean daily calcium intake 350 mg during the second to fourth week. Participants were divided into three age- and BMI-matched groups who received placebo or calcium (500 mg/day). Calcium was administered either as carbonate or calcium of dairy origin (Lactoval). There was no significant difference in weight loss in response to WM between the placebo-treated and calcium-treated groups. However, addition of calcium to the diet resulted in a lower hunger score in the Eating Inventory as well as a decrease in plasma resistin levels. Body composition measured by bioimpedance demonstrated that added calcium leads to preservation of fat-free mass. Nevertheless, a greater loss of fat-free mass in the placebo group might be partly due to a greater loss of water.     

二甲双胍对华法令诱导大鼠动脉钙化的影响及其机制初探

目的:研究二甲双胍(metformin,MET)对华法令(Warfarin,WFN)诱导大鼠动脉钙化的影响及其机制。方法:将28只SD大鼠随机分为正常对照组、8周(W)钙化组、8W钙化+8W MET 100 mg/kg治疗组、8W钙化+8W MET 200 mg/kg治疗组。采用Von Kossa染色法检测胸主动脉组织中钙结节;邻甲酚肽络合酮比色法测定颈总动脉组织中钙沉积含量;免疫组化染色检测血管壁中成骨基因Runx2及血管平滑肌标志物α-SMA的表达;Western Blot检测血管壁中Runx2及自噬标志物LC3II的表达。结果:WFN干预8 W后,大鼠动脉中钙沉积含量显著增加(P0.01),MET治疗组主动脉钙含量与钙化组相比均显著降低(P0.01)。Von Kossa染色可见钙化组(WFN组)动脉壁中层黑色连续钙盐沉积条带,而进行MET治疗后,黑色条带明显减少,对照组未见黑色条带。免疫组化显示钙化组血管壁Runx2表达阳性,棕褐色染色较深,而α-SMA表达则显著下降,基本未见棕褐色染色沉积;MET治疗后能够逆转上述趋势。Western Blot显示钙化组血管壁Runx2表达明显上升,MET治疗后Runx2表达被抑制。此外,钙化过程中伴随着自噬标志物LC3II表达轻度上升;随着MET浓度升高,血管壁中自噬水平呈剂量依赖性显著升高。结论:二甲双胍能够有效抑制大鼠动脉钙化,减轻血管平滑肌细胞由收缩表型向成骨样表型转换,其机制可能与诱导自噬有关。