Production of ex-germfree rabbits for establishment of specific pathogen-free (SPF) colonies.

Nine groups of ex-germfree (GF) rabbits were produced by inoculation of hysterectomy-derived GF rabbits with various combinations of cecal bacteria isolated from conventional (CV) rabbits in order to establish a barrier-sustained colony. Six strains of Bacteroides and two strains of Streptococcus isolated from CV rabbits (2 to 3 weeks old) were used for pretreatment. The mortality of ex-GF rabbits inoculated with the anaerobic growth (CF) on EG or SM10 plates inoculated with a 10(-5) dilution of cecal contents was 71.4 to 94.4% when given without pretreatment. All ex-GF rabbits pretreated with Bacteroides alone survived, but the mortality of ex-GF rabbits inoculated with Bacteroides plus Streptococcus strains as pretreatment was 20 and 45.4%. The mortality of ex-GF rabbits inoculated with only Bacteroides was 43%. All ex-GF rabbits inoculated with Bacteroides plus anaerobic growth (CF), cecal suspension of ex-GF mice which had been inoculated with cecal suspensions of CV rabbits (MF) or chloroform-treated cecal suspension (CHF) survived, but CHF inoculated ex-GF rabbits were in an unhealthy condition with slight diarrhoea. These data indicate that inoculation with Bacteroides strains as pretreatment plus CF or MF was required to convert GF rabbits to the normal state.     

Analysis of gender difference of cardiac risk biomarkers using hGH-transgenic mice.

We investigated gender difference in the effects of chronic exposure to human growth hormone (hGH) on cardiac risk biomarkers using transgenic mice with non-pulsatile circulating hGH. Blood plasma was obtained from transgenic and control mice at 8, 12, and 16 weeks of age, and was used for the measurement of hGH and the following cardiac risk biomarkers: total cholesterol (CHO), triglyceride (TG), HDL cholesterol (HDL), LDL cholesterol (LDL), non esterified free fatty acids (NEFA), and lipid peroxides (LPO). The hearts and the livers of transgenic mice were weighed and histopathologically examined, and the results were compared with those of control mice. Transgenic males exhibited higher levels of LDL at 8 and 12 weeks of age and higher levels of LPO at every week of age examined, as compared to those of the control males, while transgenic females exhibited somewhat lower levels of LDL and LPO from 8 to 16 weeks of age, as compared to the control females. The relative heart weight in males increased with aging and was significantly higher in the 16-week-old transgenic males compared to those of the control mice. The present results demonstrate that transgenic males had cardiac risk potential caused by chronic-exposure to hGH as compared to females. The results also show that the present transgenic mouse line is a useful model for the study of gender difference in cardiac disorders caused by hGH.     

乙酰辅酶A羧化酶抑制剂联合非诺贝特对小鼠非酒精性脂肪肝的治疗效果

摘要 目的：探讨乙酰辅酶A羧化酶抑制剂（MK-4074）联合非诺贝特对小鼠非酒精性脂肪肝（NAFLD）的脂质含量以及肝功能的改善效果。方法：20只C57BL/6小鼠给予60%高脂饲料连续喂养8周构建NAFLD小鼠模型后，随机分为安慰剂组、MK-4074组、非诺贝特组以及MK-4074联合非诺贝特治疗组，每组各5只，继续高脂喂养并分别给予安慰剂（Placebo）、MK-4074（10 mg/kg/天）、非诺贝特（30 mg/kg/天）、以及MK-4074（10 mg/kg/天）+ 非诺贝特（30 mg/kg/天）治疗持续8周。治疗结束后对小鼠体重、肝指数、肝脏脂质含量、肝功能以及肝脏病理和肝脏中性粒细胞和巨噬细胞浸润情况进行分析。结果：与安慰剂组相比，单用MK-4074治疗可显著降低肝指数、肝脏甘油三酯（TG）、胆固醇（TC）、非酯化脂肪酸（NEFA）的含量以及血清ALT和AST水平，而对小鼠体重和血清TC没有显著影响；单用非诺贝特可显著降低小鼠体重，肝脏TG、TC、NEFA以及血清TG、 ALT和AST水平，对小鼠的肝指数、血清TC没有显著影响；而MK-4074与非诺贝特联合治疗可显著降低小鼠体重、肝脏TG、TC、NEFA，以及血清TG、ALT和AST水平，降低肝脏脂质积累以及中性粒细胞与巨噬细胞浸润，效果优于MK-4074或非诺贝特单药治疗。结论：MK-4074联合非诺贝特可显著减少NAFLD小鼠肝脏的脂质含量，改善肝功能。     

Characteristic faecal flora of NC mice

The composition of faecal flora of NC mice was compared with that of CF #1 mice. NC- and CF #1-germfree (GF) mice were cage-mated with NC- or CF #1-conventional (CV) mice in an isolator. The faecal flora of these ex-GF mice was dependent on the recipient mouse strain modifying colonization by the donor mouse bacteria. Although NC- and CF #1-pups removed by hysterectomy were fostered to different strains, almost all these mice at 8 weeks old had a strain characteristic pattern of faecal flora regardless of the foster strains. In GF mice mono-associated with a Lactobacillus strain or a Bifidobacterium strain isolated from faeces of CV mice, the numbers of these bacteria in the stomach and small intestine of NC mice were lower than those of CF #1 mice. In GF mice associated with chloroform-treated faeces of CV mice, and a Lactobacillus strain or a Bifidobacterium strain, the numbers of these bacteria in the stomach and all parts of the intestine of NC mice were considerably lower than those of CF #1 mice. These results suggested that the composition of faecal flora of NC mice were characteristic, i.e. the fact that the numbers of lactobacilli were low compared with CF #1 mice with ordinary faecal flora and the colonization of bifidobacteria, peptococcaceae and eubacteria on ES agar in NC mice intestine differed, was due to genetic factors.     

东方田鼠非酒精性脂肪肝模型的建立

目的建立东方田鼠非酒精性脂肪肝模型,并观察测定其肝指数、病理、血清生化指标的动态变化。方法选取6周龄湖南洞庭湖种群雄性东方田鼠70只,随机分为2组,模型组饲喂高脂肪料,对照组饲喂高纤维料,分别于第2、4、6、8、12周处死,称量体重及肝重,计算肝指数,采血检测东方田鼠血清丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)、碱性磷酸酶(ALP)、r-谷氨酰转移酶(r-GT)、胆碱酯酶(CHE)、甘油三酯(TG)、总胆固醇(TC)、游离脂肪酸(FFA)、葡萄糖(GLU)、高密度脂蛋白(HDL)和低密度脂蛋白(LDL),并取肝脏HE染色后做病理学观察。结果与对照组相比,模型组6周时肝脏出现了典型的脂肪肝特征,肝重和肝指数都明显升高(P<0.05),血清ALT、AST、r-GT、CHE、TC、FFA、GLU和LDL都明显升高(P<0.05),HDL和TG均明显降低(P<0.05)。镜检观察到模型组田鼠肝细胞逐渐呈现弥漫性脂肪变性,6周时大范围出现脂滴,8周时肝内出现弥漫性大脂肪滴,12周后出现炎细胞的浸润。结论采用高脂饲料成功诱发东方田鼠非酒精性脂肪肝,可为研究非酒精性脂肪肝的发病机制和药物干预提供新的模型。     

Atropine inhibits the degranulation of Paneth cells in ex-germ-free mice

Summary Previous studies have shown that the secretory products of Paneth cells contain antibacterial agents (lysozyme, IgA) that are affected by the bacterial milieu in the intestine. To investigate whether Paneth-cell secretion is controlled via cholinergic mechanisms, the ultrastructure of Paneth cells was studied in four animal groups: (1) germfree (GF) control mice (Jcl: ICR [GN], male, 13 weeks old), (2) GF mice injected subcutaneously with atropine sulfate (200 mg/kg body weight, dissolved in physiological saline 20 mg/ml), (3) ex-GF mice inoculated with feces from specific-pathogen-free (SPF) mice, and (4) ex-GF mice injected with atropine and inoculated with feces from SPF mice. In ex-GF mice inoculated with feces, 70–90% of the Paneth cells showed fewer secretory granules than those from GF mice (p<0.01). Approximately 30% of the Paneth cells had a large vacuole (3–10 m diameter) in the apical cytoplasm. Exocytosed electron-dense material from secretory granules was observed in a few crypt lumens. In ex-GF mice inoculated with feces and given atropine, about 90% of the Paneth cells contained numerous secretory granules, like those in GF control mice, but vacuolated Paneth cells and exocytotic figures were rare; thus the secretion of Paneth cells was blocked by atropine. It is therefore possible that the bacterial milieu in the intestine affects the secretory activity of Paneth cells via cholinergic mechanisms.     

非酒精性脂肪性肝病与MTP关系的实验研究

目的：探讨非酒精性脂肪性肝病( Non-alcoholic fatty liver disease, NAFLD)与微粒体甘油三酯转运蛋白(microsomal triglyceridetransfer protein,MTP）的关系。方法：将雄性Wistar 大鼠60只随机分为正常对照组（A 组）、高脂组（B 组）和MTP 抑制剂组（C 组）,每组各20 只。B 组、C组给予高脂饲料喂养,8 周后确认非酒精性脂肪肝建模成功,C组大鼠给予混有特异性小肠MTP抑制 剂JTT-130 的高脂饲料喂养,B 组大鼠建模过程始终喂养高脂饲料,A 组大鼠喂养普通饲料。于第12周,分别测定大鼠血清甘油 三酯(triglyceride,TG)、总胆固醇(total cholesterol,TC)、高密度脂蛋白胆固醇(high density lipoprotein-cholesterol,HDL-c)含量,以及 肝脏TC、TG、磷脂含量。同时测定肝脏中微粒体甘油三酯转运蛋白(MTP) 的活性与mRNA 表达量。结果：与正常对照组（A组）相 比,高脂组（B组）大鼠血清TC、TG、HDL-c 浓度和肝脏TC、TG含量明显提高（P＜0.05）,MTP 活性及mRNA 水平明显下调（P＜ 0.05）。与高脂组（B 组）比较,MTP 抑制剂组（C 组）大鼠血清TC、TG、HDL-c 浓度和肝脏TC、TG 含量明显下降（P＜0.05）,而 MTP 活性及mRNA 表达量比较无明显差别（P＞0.05）。结论：非酒精性脂肪性肝病存在MTP表达下调,特异性小肠MTP 抑制剂 JTT-130 可以有效抑制肠道对TG的转运,不影响肝脏TG分泌,并在降低高脂大鼠血浆TG和胆固醇水平的同时也降低肝脏TG 含量。     

Patterns of early gut colonization shape future immune responses of the host

The most important trigger for immune system development is the exposure to microbial components immediately after birth. Moreover, targeted manipulation of the microbiota can be used to change host susceptibility to immune-mediated diseases. Our aim was to analyze how differences in early gut colonization patterns change the composition of the resident microbiota and future immune system reactivity. Germ-free (GF) mice were either inoculated by single oral gavage of caecal content or let colonized by co-housing with specific pathogen-free (SPF) mice at different time points in the postnatal period. The microbiota composition was analyzed by denaturing gradient gel electrophoresis for 16S rRNA gene followed by principal component analysis. Furthermore, immune functions and cytokine concentrations were analyzed using flow cytometry, ELISA or multiplex bead assay. We found that a single oral inoculation of GF mice at three weeks of age permanently changed the gut microbiota composition, which was not possible to achieve at one week of age. Interestingly, the ex-GF mice inoculated at three weeks of age were also the only mice with an increased pro-inflammatory immune response. In contrast, the composition of the gut microbiota of ex-GF mice that were co-housed with SPF mice at different time points was similar to the gut microbiota in the barrier maintained SPF mice. The existence of a short GF postnatal period permanently changed levels of systemic regulatory T cells, NK and NKT cells, and cytokine production. In conclusion, a time window exists that enables the artificial colonization of GF mice by a single oral dose of caecal content, which may modify the future immune phenotype of the host. Moreover, delayed microbial colonization of the gut causes permanent changes in the immune system.     

The gastrointestinal microbiota affects the selenium status and selenoprotein expression in mice

Colonization of germ-free (GF) mice has been shown to induce the gastrointestinal form of the selenium-dependent glutathione peroxidases, GPx2. Since bacterial colonization of the gastrointestinal tract is associated with stress, we aimed to clarify how bacteria affect selenoprotein expression in unstressed conditions. GF and conventional (CV) FVB/NHan(TMHsd) mice were fed a selenium-poor (0.086 ppm) or a selenium-adequate (0.15 ppm) diet for 5 weeks starting from weaning. Each group consisted of five animals. Specific glutathione peroxidase (GPx) and thioredoxin reductase (TrxR) expression was measured in plasma, liver and intestinal sections by activity, protein and mRNA level as appropriate. Under selenium-adequate conditions, selenoprotein expression did not differ in GF and CV mice. Under selenium-limiting conditions, however, GF mice generally contained higher GPx and TrxR activities in the intestine and liver, higher GPx1 protein and RNA levels in the liver, higher GPx2 protein levels in the proximal and distal jejunum and colon and higher GPx1 and GPx2 RNA levels in the colon. In addition, higher selenium concentrations were estimated in plasma, liver and cecum. All differences were significant. It is concluded that bacteria may compete with the host for selenium when availability becomes limiting. A variable association with different microorganisms might influence the daily requirement of mice for selenium. Whether the microbiota also affects the human selenoprotein status appears worthy of investigation.     

有氧运动与饮食控制对2型糖尿病大鼠肝chemerin及其受体CMKLR1的影响

目的：研究4周有氧运动与饮食控制对2型糖尿病（DM）大鼠肝chemerin及其受体趋化因子样受体1（CMKLR1）的影响及其在改善糖脂代谢中的影响。方法：50只雄性SD大鼠随机分为正常对照组（Con,n=6）和糖尿病造模组（n=44）。采用高脂高糖饲料联合小剂量链脲佐菌素（STZ）（30 mg/kg）的方法制备2型糖尿病模型大鼠。造模成功的DM大鼠随机分为4组（n=6）：糖尿病对照组（DM）、糖尿病运动组（EDM）、改喂普通饲料的糖尿病饮食控制组（NDM）和糖尿病运动+饮食控制组（ENDM）。运动组大鼠进行为期4周中等强度跑台有氧运动,每周运动6 d。采用罗氏血糖仪检测大鼠空腹血糖（FBG）,全自动生化分析仪检测大鼠血清总胆固醇（TC）、甘油三酯（TG）和低密度脂蛋白（LDL）水平,real time PCR和Western blot分别检测大鼠肝chemerin、CMKLR1的mRNA和蛋白水平。结果：DM大鼠FBG和血清TC、TG、LDL水平显著升高的同时,肝chemerin和CMKLR1的mRNA和蛋白水平显著增加;4周有氧运动和/或饮食控制显著降低EDM、NDM和ENDM组FBG和血清TC、TG、LDL的同时,显著降低这3组大鼠的肝chemerin蛋白水平,其中ENDM组降低最显著（P<0.01）;NDM和ENDM组大鼠的肝CMKLR1蛋白水平升高（P<0.01）。结论：4周有氧运动和/或饮食控制降低2型糖尿病大鼠的肝chemerin蛋白水平、增加CMKLR1蛋白水平,这可能与其改善糖尿病大鼠的糖脂代谢有关。     

番茄皂苷A对小鼠血脂及肝脏脂肪的作用

该研究以ApoE基因缺陷小鼠和高脂饲料诱导的高血脂症模型小鼠为对象,采用药理学方法研究了番茄皂苷A对血脂及肝脏脂肪的调节作用。在ApoE基因缺陷小鼠和高脂饲料诱导的高血脂症模型小鼠中,通过灌胃给予番茄皂苷A:取血,测定血清中总胆固醇(TC)、甘油三酯(TG)、高密度脂蛋白胆固醇(HDLC)、低密度脂蛋白胆固醇(LDLC)、谷丙转氨酶(ALT)、谷草转氨酶(AST)、尿素氮(BUN)、肌酐(Cr)、葡萄糖(Glu)的含量和活性;处死小鼠后,取肝脏称重,计算肝脏指数;精确称取一部分肝脏,测定肝脏脂质的含量。结果表明:番茄皂苷A对ApoE基因缺陷小鼠可以降低血清TC、HDLC、LDLC的含量,对ALT、AST、BUN、Cr、Glu没有影响,说明番茄皂苷A可以降低ApoE基因缺陷小鼠血中胆固醇含量,对血糖没有影响,对肝肾功能无影响;对高脂饲料诱导的高血脂症模型小鼠,可以降低血清TC、HDLC的含量,可以降低肝脏TC的含量,对ALT、AST、BUN、Cr、Glu没有影响,说明番茄皂苷A可以改善高脂饲料诱导的高血脂症模型小鼠的脂质代谢,且对肝肾功能无影响。该研究结果表明番茄皂苷A具有一定的降低胆固醇的作用,且不影响肝肾功能。     

Traditional Chinese Medicine improves dysfunction of peroxisome proliferator-activated receptor alpha and microsomal triglyceride transfer protein on abnormalities in lipid metabolism in ethanol-fed rats

We report the effects of Traditional Chinese Medicine (TCM) on alcohol-induced fatty liver in rats. TCM consists of Astragalus membranaceus, Morus alba, Crataegus pinnatifida, Alisma oriental, Salvia miltiorrhiza and Pueraria lobata. The rats were separated randomly into five groups; the CD group (n=10), which was fed a control diet for 10 weeks, the ED group (n=10), which was fed an isocaloric liquid diet containing ethanol for 10 weeks and given daily oral doses of TCM (0.222 g/kg/day; TCM222, 0.667 g/kg/day; TCM667, and 2.000 g/kg/day; TCM2000, n=10, respectively) over the last four weeks of the study. The ED group developed fatty livers, as determined by their lipid profiles and liver histological findings. Compared with the control group, liver/body weight, plasma triglyceride (TG) and total cholesterol (TC), liver TG and TC, plasma alanine aminotransferase (ALT) and aspartic aminotransferase (AST) significantly increased in the ED group. Also, free fatty acids (FFA) levels increased in both plasma and liver during the administration of ethanol. On the other hand, when rats were administrated with TCM, their liver/body weight, plasma TG, TC and FFA, liver TG, TC and FFA, plasma ALT and AST decreased significantly and the degree of hepatic lipid droplets was markedly improved compared with those in the ED group. Proper function of the peroxisome proliferator-activated receptor alpha (PPARalpha) is essential for the regulation of hepatic fatty acid metabolism. Microsomal triglyceride transfer protein (MTP) is essential for the secretion of triglycerides from the liver. mRNAs for PPARalpha and MTP were reduced in the livers of ethanol-fed rats. TCM restored the mRNA levels of PPARalpha and MTP, and prevented development of fatty livers in ethanol-fed rats. Impairment of PPARalpha and MTP function during ethanol consumption contributes to the development of alcohol-induced fatty liver, which can be overcome by TCM.     

Differential effect of Bacillus firmus on immune response and enterocyte brush-border enzyme levels in BALB/c and B10.BR mice

A nonpathogenic bacterium of external environment possessing remarkable immunomodulatory activity, Bacillus firmus (BF) inactivated with formaldehyde, was given intragastrically to two genetically different mouse strains BALB/c (H-2d) and B10.BR/SnPh (B10.BR, H-2k) reared in conventional (CV) and B10.BR strain also in germ-free (GF) conditions. Repeated intragastric administration of BF (500 micrograms every other day over two weeks, starting at the age of 3 months) significantly enhanced intestinal IgA levels in CV BALB/c mice but did not affect intestinal IgA in CV B10.BR mice. In GF B10.BR mice, IgG levels in sera and intestinal washings increased after BF administration compared to CV B10.BR mice. In CV BALB/c mice, specific activity of enterocyte brush-border enzymes (lactase, gamma-glutamyltransferase, alkaline phosphatase) decreased after BF treatment; sucrase (sucrose alpha-glucosidase) activity was not affected. On the other hand, in B10.BR mice, specific activity of gamma-glutamyltransferase and dipeptidyl peptidase IV were higher after administration of BF in both CV and GF groups relative to untreated controls. The activities of lactase and glucoamylase (glucan 1,4-alpha-glucosidase) were significantly stimulated only in the group of GF B10.BR mice treated with formolized BF. The stimulation of immunoglobulin production after BF treatment was accompanied by changes in the levels of enterocyte brush-border enzymes; this responsiveness to BF treatment was genetically regulated.     

Plasma lipids and apolipoproteins A and B in human pregnancy

A cross sectional study was carried out in 200 normal pregnant women between 8-40th weeks of gestation, 25 women during delivery and 25 women 6 weeks after delivery. Plasma and lipoprotein lipids were measured using standard procedures. Apolipoprotein A (Apo A) and Apolipoprotein B (Apo B), were measured by electroimmunoassay. Plasma levels of Apo A were elevated in pregnant women but the elevations were not significant until 17-20 weeks of gestation. Apo A during pregnancy was significantly correlated (p less than 0.001) with high density lipoprotein cholesterol (HDL-C). The level of Apo B increased progressively during pregnancy and it was significantly correlated (p less than 0.001) with total cholesterol (TC), plasma triglycerides (TG) and phospholipids (PL). Apo A and Apo B levels returned to non pregnant values within the puerperium, whereas TC, TG and PL remained significantly elevated above controls (p less than 0.01) 6 weeks post partum.     

ANGPTL4 silencing via antisense oligonucleotides reduces plasma triglycerides and glucose in mice without causing lymphadenopathy

Angiopoietin-like 4 (ANGPTL4) is an important regulator of plasma triglyceride (TG) levels and an attractive pharmacological target for lowering plasma lipids and reducing cardiovascular risk. Here, we aimed to study the efficacy and safety of silencing ANGPTL4 in the livers of mice using hepatocyte-targeting GalNAc-conjugated antisense oligonucleotides (ASOs). Compared with injections with negative control ASO, four injections of two different doses of ANGPTL4 ASO over 2 weeks markedly downregulated ANGPTL4 levels in liver and adipose tissue, which was associated with significantly higher adipose LPL activity and lower plasma TGs in fed and fasted mice, as well as lower plasma glucose levels in fed mice. In separate experiments, injection of two different doses of ANGPTL4 ASO over 20 weeks of high-fat feeding reduced hepatic and adipose ANGPTL4 levels but did not trigger mesenteric lymphadenopathy, an acute phase response, chylous ascites, or any other pathological phenotypes. Compared with mice injected with negative control ASO, mice injected with ANGPTL4 ASO showed reduced food intake, reduced weight gain, and improved glucose tolerance. In addition, they exhibited lower plasma TGs, total cholesterol, LDL-C, glucose, serum amyloid A, and liver TG levels. By contrast, no significant difference in plasma alanine aminotransferase activity was observed. Overall, these data suggest that ASOs targeting ANGPTL4 effectively reduce plasma TG levels in mice without raising major safety concerns.     

大黄素降糖及改善脂质代谢的实验研究

目的：探讨大黄素对2型糖尿病模型db/db小鼠血糖及血脂水平的影响。方法：4周龄16只db/db雄性小鼠随机分为治疗组和对照组,每组8只;治疗组经灌胃每天给予100mg/kg大黄素;对照组灌胃给予相仿体积的生理盐水,开始10天每天算进食量,每周测空腹血糖及体重1次,连续干预8周,干预前及实验结束前1周测胰岛素耐量,干预结束后于颈动脉取血测血脂水平（HDL-C、LDL-C、TG、TC）。结果：①大黄素干预不影响db/db小鼠的进食量,与对照组比较,P〉0.05;②大黄素可显著减轻db/db小鼠体重,与对照组比较,P〈0.05;③大黄素可改善db/db小鼠胰岛素敏感性,降低小鼠的空腹血糖水平,与对照组比较,P〈0.05或P〈0.01;④大黄素可降低db/db小鼠血TG、TC、LDL-C水平,P〈0.01。结论：大黄素可有效地改善db/db小鼠的糖脂紊乱状态,其降糖及改善血脂代谢机制值得进一步深入研究。     

Induction and evaluation of atherosclerosis in New Zealand white rabbits

Atherosclerosis was experimentally induced in New Zealand white rabbits by feeding a high cholesterol diet for 12 weeks for screening of drugs against atherosclerosis. After 12 weeks, blood was collected from ear vein for evaluation of total cholesterol (TC), triglyceride (TG), low density lipoprotein (LDL) and very low density lipoprotein (VLDL) levels, then the animals were sacrificed to collect the livers for estimation of cholesterol, and aorta for gross and histopathological evaluations. The elevated levels of serum and liver parameters accompanied by gross and histopathological changes like accumulation of foam cells, atheromatous plaque formation and replacement fibrosis supported the successful induction of atherosclerosis in New Zealand white rabbits.     

熊果酸对糖尿病小鼠肝损伤的作用及其可能机制

目的：研究熊果酸对高脂饲料联合链脲佐菌素（STZ）诱导的糖尿病小鼠肝损伤的影响,探讨其可能的作用机制。方法：随机选取20只小鼠高脂饲料喂养6周后,STZ （30 mg/kg）腹腔注射连续5 d,9 d后测空腹血糖,大于11.1 mmol/L视为糖尿病模型,将其随机分为模型组和熊果酸组（100 mg/kg）（n=10）;另取10只小鼠设为对照组。连续给药8周。小鼠称重,测定空腹血糖（FBG）,血清总胆固醇（TC）、甘油三酯（TG）含量,谷丙转氨酶（ALT）、谷草转氨酶（AST）、超氧化物歧化酶（SOD）活性,丙二醛（MDA）含量,HE染色观察肝组织病理变化。结果：模型组与对照组比较,FBG、血清TC、TG含量,ALT、AST活性、MDA含量明显升高（P<0.05,P<0.01）;SOD活性明显降低（P<0.01）;HE染色显示部分肝细胞水肿,轻度脂肪变性,门管区可见淋巴细胞浸润。熊果酸组与模型组比较,FBG,血清TC、TG含量,ALT、AST活性、MDA含量明显降低（P<0.05,P<0.01）;SOD活性明显升高（P<0.01）;HE染色显示熊果酸组肝细胞排列较为整齐,水肿不明显,淋巴细胞少量存在。结论：熊果酸对高脂饲料联合STZ诱导的糖尿病小鼠肝损伤具有保护作用,其机制可能与降血糖、调节血脂、降低肝组织氧化应激水平,提高肝脏抗氧化能力有关。     

The effects of chromium picolinate on glucose and lipid metabolism in running rats

BackgroundChromium picolinate (CrPic) is commonly used to reduce muscle fatigue after exercise. We aimed to elucidate the effects of CrPic on glucose and lipid metabolism and the expression of glucose transporters in exercised rats.MethodsForty-two male Wistar rats (8-week-old) were distributed into six groups (n = 7) as follows: Control, CrPic, Chronic Exercise (CEx), CEx + CrPic, Acute Exercise (AEx), and AEx + CrPic. CEx consists of 30 m/min, 30 min/day, and 5 days/week for 6 weeks. CrPic was supplemented at 400 μg elemental Cr/kg of diet for 6 weeks. In the AEx groups, animals were run on the treadmill at 30 m/min until exhaustion.ResultsCEx significantly lowered blood glucose (BG), total cholesterol (TC) and triglyceride (TG) levels, but elevated insulin concentration (IC), compared with control (P < 0.05). CEx significantly decreased the level of malondialdehyde (MDA) in the serum, liver, and muscle while AEx elevated it (P < 0.001 for all). CrPic significantly decreased BG, TC, TG levels, and increased IC with a remarkable effect in CEx rats (P < 0.01). CrPic also significantly reduced serum, liver, and muscle MDA levels (P < 0.001). Both AEx and CEx increased the expression of liver glucose transporter 2 (GLUT-2) and muscle GLUT-4 with the highest level in CEx rats (P < 0.05). Moreover, CrPic supplementation significantly elevated GLUT-2 and GLUT-4 expressions in the liver and muscle of sedentary and exercise-treated rats (P < 0.05).ConclusionCrPic improves various metabolic parameters and reduces oxidative stress in CEx and AEx rats by decreasing BG, TC, TG, MDA levels in serum and elevating GLUT-2 and GLUT-4 expression in the liver and muscle samples. The efficacy of CrPic was more pronounced in CEx rats.