SAM肝细胞色素P450 3A对衰老的作用

为探讨衰老与细胞色素Ｐ４５０３Ａ（ＣＹＰ３Ａ）活性的关系,用红霉素Ｎ－脱甲酶活性测定法分别检测了ＳＡＭ－Ｒ１、ＳＡＭ－Ｐ１和ＳＡＭ－Ｐ８三组衰老加速鼠（ＳＡＭ）中肝微粒体细胞色素Ｐ４５０３Ａ的活性,每组动物分为７、１３、３６周龄组。结果发现ＳＡＭ随年龄增长ＣＹＰ３Ａ的活性均降低,１３周龄组尤为显著,ＳＡＭ－Ｒ１组ＣＹＰ３Ａ活性下降约７２％（ｔ＝２６１,Ｐ＜００２）;ＳＡＭ－Ｐ１组ＣＹＰ３Ａ活性下降约７３％（ｔ＝２．７４,Ｐ＜００２）;ＳＡＭ－Ｐ８组中ＣＹＰ３Ａ活性降低约８６％（ｔ＝３．１４,ｐ＜０．００５）。ＳＡＭ－Ｐ１组ＣＹＰ３Ａ活性３６周龄比３周龄组下降约３５％,呈缓慢进行;ＳＡＭ－Ｒ１和ＳＡＭ－Ｐ８组中１３至３６周龄组均无明显变化。提示细胞色素Ｐ４５０３Ａ对衰老有重要影响作用。     

Long-term intake of fish oil increases oxidative stress and decreases lifespan in senescence-accelerated mice

Objective

The effects of fish oil including ω-3 polyunsaturated fatty acids on aging and lifespan are not well understood. In this study, the influence of long-term ingestion of fish oil on lifespan was examined in senescence-accelerated (SAMP8) mice.

Methods

We investigated the effects of dietary fish oil on lifespan and on lipid composition and oxidative stress in plasma and liver in SAMP8 mice. Male mice were fed a fish oil diet (5% fish oil and 5% safflower oil) or a safflower oil diet (10% safflower oil) from 12 wk of age.

Results

The SAMP8 mice fed fish oil did not have a longer maximum lifespan and had a shorter average lifespan than mice fed safflower oil. To examine the mechanism underlying these results, the effects on oxidative stress of long-term ingestion of fish oil were also examined. SAMP8 mice fed fish oil for 28 wk showed strong oxidative stress that caused hyperoxidation of membrane phospholipids and a diminished antioxidant defense system due to a decrease in tocopherol compared with mice fed safflower oil.

Conclusion

These findings suggest that intake of fish oil increases oxidative stress, decreases cellular function, and causes organ dysfunction in SAMP8 mice, thereby promoting aging and shortening the lifespan of the mice.     

Consumption of a high glycemic index diet increases abdominal adiposity but does not influence adipose tissue pro-oxidant and antioxidant gene expression in C57BL/6 mice

The hypothesis of this study is that consumption of a high glycemic index (GI) starch will increase adiposity, increase expression of the pro-oxidant enzyme (nicotinamide adenine dinucleotide phosphate [NADPH] oxidase), and decrease expression of the antioxidant enzymes (catalase, glutathione peroxidase [GPx], and superoxide dismutase [SOD]) in adipose tissue of mice. C57BL/6 mice (n = 5-8/group) were fed a diet containing either high-GI starch (100% amylopectin) or low-GI starch (60% amylose/40% amylopectin) under low-fat (LF) or high-fat (HF) conditions for 16 weeks. Meal tolerance tests (MTTs) indicated that the postprandial blood glucose response over 120 minutes for the high-GI mice under LF and HF conditions was significantly greater than for mice fed low-GI diets. This result was not due to increased food consumption by the high-GI mice during the MTT. Although there was no difference in body weight between mice fed high-GI or low-GI starch, LF high-GI mice had significantly greater adiposity compared to LF low-GI mice. High-fat mice had a significant increase in NADPH oxidase expression compared to LF mice, but there was no significant effect of starch on NADPH oxidase expression. High-fat diet significantly decreased the expression of GPx and catalase, but there was no significant effect of starch on GPx and catalase expression. There was no difference in SOD expression among any of the diet groups. In conclusion, high GI diets increase adiposity under LF conditions but do not influence pro-oxidant or antioxidant enzyme gene expression in adipose tissue of C57BL/6 mice.     

D-半乳糖模型鼠与自然衰老鼠的比较研究

目的比较应用于衰老相关研究的D-半乳糖模型鼠与自然衰老鼠各种衰老指标的异同。方法采用昆明鼠作为受试动物,将动物分为3组:1.5月龄鼠给予D-半乳糖45天作为D-半乳糖模型组;15月龄鼠作为自然衰老组;3月龄鼠作为正常对照组。对3组动物分别进行了免疫(迟发型变态反应、半数溶血值的测定、抗体生成细胞检测和NK细胞活性测定)、生化[丙二醛(MDA)测定、超氧化物歧化酶(SOD)活力测定及SODmRNA的测定和SOD蛋白的测定]、行为(小鼠水迷宫试验和神经递质测定)、病理(常规病理和免疫组化蛋白测定)等多项指标的测定和分析。结果自然衰老组半数溶血值与正常对照组比较明显降低(P<0.05),而D-半乳糖模型组与对照组比较无明显差异。D-半乳糖模型组和自然衰老组SOD活性均低于对照组(P<0.01)、MDA含量均高于对照组(P<0.05,P<0.01),两组间无明显差异。行为学试验显示,自然衰老组与正常对照组相比不同测试阶段游泳时间延长,D-半乳糖衰老模型组与正常对照组相比无明显差异,自然衰老组脑组织肾上腺素(E)和组织多巴胺(DA)均降低(P<0.05,P<0.01),D-半乳糖模型组脑组织E和DA降低不明显,神经递质的改变与行为试验结果一致;自然衰老组和D-半乳糖模型SOD基因表达均低于正常对照组(P<0.05),其SODmRNA含量降低与SOD活性、SOD蛋白表达水平降低一致。结论D-半乳糖模型鼠虽然某些指标接近自然衰老鼠,但免疫、行为等方面与自然衰老鼠相比尚存在较大差异。D-半乳糖模型鼠是由化学损伤造成的,难以真实反映衰老的生理生化改变。因此D-半乳糖模型鼠可能不宜应用于免疫、行为等方面的衰老研究。     

8-羟基脱氧鸟嘌呤在慢性砷暴露小鼠心肌细胞中的表达

目的通过检测核酸损伤标志物8-羟基脱氧鸟嘌呤(8-OHdG)在砷暴露小鼠心肌细胞中的表达,为探讨砷的心脏毒性作用机制提供参考依据。方法昆明种小鼠40只,随机分为4组:1、2、4mg/L三氧化二砷染毒组和生理盐水对照组。自然饮水方式连续染毒60 d,取小鼠心脏组织固定,采用HE染色和免疫组化方法观察心肌组织的病理变化和心肌细胞的8-OHdG表达。结果染砷组心肌细胞出现核肿胀、部分核质溶解等病理改变,且其心肌细胞出现明显的8-OHdG表达,并随着砷暴露剂量的增加呈现剂量-反应关系。结论砷可导致心肌细胞的核酸损伤和病理学改变,其损伤的程度与砷的暴露剂量有关。     

石榴皮提取物对高脂血症小鼠抗氧化功能和脂质代谢于的影响

目的：探讨石榴果皮提取物对高脂血症小鼠抗氧化功能和脂质代谢的影响，并与果汁提取物相比较。方法：采用高脂饲料喂养C57BL／6J小鼠建立动物模型，观察提取物对抗氧化功能、血脂、肝脏脂类含量以及主动脉壁形态学的影响。结果：石榴果皮提取物可以有效改善抗氧化功能，降低血脂及肝脏脂肪和胆固醇含量，抑制主动脉动脉粥样硬化（AS）早期病变，石榴果汁提取物也有同样作用。结论：石榴果皮提取物能够抑制AS早期病变，可能与提高抗氧化功能、降低血脂有关。     

石榴皮提取物对高脂血症小鼠抗氧化功能和脂质代谢的影响

目的:探讨石榴果皮提取物对高脂血症小鼠抗氧化功能和脂质代谢的影响,并与果汁提取物相比较。方法:采用高脂饲料喂养C57BL/6J小鼠建立动物模型,观察提取物对抗氧化功能、血脂、肝脏脂类含量以及主动脉壁形态学的影响。结果:石榴果皮提取物可以有效改善抗氧化功能,降低血脂及肝脏脂肪和胆固醇含量,抑制主动脉动脉粥样硬化(AS)早期病变,石榴果汁提取物也有同样作用。结论:石榴果皮提取物能够抑制AS早期病变,可能与提高抗氧化功能、降低血脂有关。     

A lifelong exposure to a Western-style diet,but not aging,alters global DNA methylation in mouse colon

BACKGROUND/OBJECTIVESPrevious studies have indicated that when compared to young mice, old mice have lower global DNA methylation and higher p16 promoter methylation in colonic mucosa, which is a common finding in colon cancer. It is also known that a Western-style diet (WSD) high in fat and calories, and low in calcium, vitamin D, fiber, methionine and choline (based on the AIN 76A diet) is tumorigenic in colons of mice. Because DNA methylation is modifiable by diet, we investigate whether a WSD disrupts DNA methylation patterns, creating a tumorigenic environment.SUBJECTVIES/METHODSWe investigated the effects of a WSD and aging on global and p16 promoter DNA methylation in the colon. Two month old male C57BL/6 mice were fed either a WSD or a control diet (AIN76A) for 6, 12 or 17 months. Global DNA methylation, p16 promoter methylation and p16 expression were determined by LC/MS, methyl-specific PCR and real time RT-PCR, respectively.RESULTSThe WSD group demonstrated significantly decreased global DNA methylation compared with the control at 17 months (4.05 vs 4.31%, P = 0.019). While both diets did not change global DNA methylation over time, mice fed the WSD had lower global methylation relative to controls when comparing all animals (4.13 vs 4.30%, P = 0.0005). There was an increase in p16 promoter methylation from 6 to 17 months in both diet groups (P < 0.05) but no differences were observed between diet groups. Expression of p16 increased with age in both control and WSD groups.CONCLUSIONSIn this model a WSD reduces global DNA methylation, whereas aging itself has no affect. Although the epigenetic effect of aging was not strong enough to alter global DNA methylation, changes in promoter-specific methylation and gene expression occurred with aging regardless of diet, demonstrating the complexity of epigenetic patterns.     

硫辛酸对高脂饲料小鼠氧化应激与糖、脂代谢基因表达的影响

目的探讨硫辛酸(LA)对高脂饲料小鼠血糖、血脂代谢和抗氧化能力的影响。方法24只C57BL/6雄性小鼠,随机分为3组:即对照组(正常饲料),高脂组(高脂饲料),LA组(高脂饲料+0.1%LA),6周后测定空腹血糖(FPG)、胰岛素(FINS)、甘油三酯(TG)、总胆固醇(TC)等糖脂代谢指标以及丙二醛(MDA)、超氧化物歧化酶(SOD)和总抗氧化能力(TAC)等抗氧化指标,同时用Affymetrix MOE430A基因芯片分析肝脏抗氧化、糖脂代谢相关功能基因的表达。结果与高脂组相比,LA组MDA含量显著降低,TAC明显升高(P<0.05)。LA显著降低血浆TG、TC、LDL-C和FPG、FINS的水平(P<0.05),MDA含量与HDL-C/TC(r=-0.47,P<0.05)和胰岛素抵抗指数(r=0.74,P<0.05)显著相关。硫辛酸改变高脂组自由基/氧化应激、糖脂代谢相关通路大部分响应基因的表达水平。结论高脂引发氧化-抗氧化系统失衡,硫辛酸通过直接清除自由基以及恢复自由基/氧化应激通路相关基因的表达水平解除氧化应激而有助于防治高脂引发的糖脂代谢紊乱。