β1肾上腺素能受体阻断剂与β2肾上腺素能受体激动剂联用对心力衰竭大鼠心功能及心肌细胞凋亡的影响

目的 在一定范围内激活β2肾上腺素能受体（AR）可以在不加重心室重构的前提下改善心力衰竭（心衰）大鼠心功能,推测β1AR阻断剂联合β2AR激动剂有可能进一步改善心衰大鼠心功能并减轻心肌细胞凋亡,该实验对此进行了研究并探讨了其机制。方法 随机选取9只雄性Wistar大鼠为对照组。将异丙基肾上腺素诱导的心衰大鼠随机分为美托洛尔组（n=11）,联合治疗组（n=11）,安慰剂组（n=10）。美托洛尔组给予美托洛尔50mg／kg,一日两次灌胃。联合治疗组给予非诺特罗125μg／kg,美托洛尔50mg／kg一日两次灌胃。安慰剂组给予等量生理盐水一日两次灌胃。对照组不予处理。治疗8周后应用超声心动图评价心功能,TUNEL法检测心肌细胞凋亡指数,测定Caspase-3酶活性,Westernblot测定bcl-2及bax蛋白质表达,测定脏器重量／体重,组织病理学测定胶原容积分数（CVF）。结果 （1）美托洛尔组及联合治疗组均较安慰剂组左室舒张末期直径（LVEDd）、左室收缩末期直径（LVESd）、E峰A峰比值（E／A）明显下降,短轴缩短率（FS）、射血分数（EF）则有明显增高。联合治疗组较美托洛尔组LVEDd、LVESd有进一步降低（均为P〈0．05）,FS、EF则有进一步增高（均为P〈0．01）。（2）美托洛尔组及联合治疗组较安慰剂组左室重量体重比（LVW／BW）、肺脏重量体重比（PW／BW）及CVF明显降低（均为P〈0．01）。联合治疗组LVW／BW及PW／BW较美托洛尔组进一步降低（P〈0．01）,但两组之间CVF无显著差异。（3）美托洛尔组及联合治疗组较安慰剂组心肌细胞凋亡指数（AI）及Caspase．3活性均有明显减低。联合治疗组较美托洛尔组有进一步减低（均为P〈0．01）。（4）与安慰剂组相比,美托洛尔组及联合治疗组bax蛋白表达有明显下降而bcl-2／bax显著升高,并且以联合治疗组改善更为显著（均为P〈0．01）。结论 β1AR阻断剂联合β2AR激动剂较单用β1AR阻断剂进一步改善心衰大鼠的心功能,减轻心室重构。明显降低bax蛋白表达及bcl-2／bax,减轻心肌细胞凋亡很可能是其疗效提高的机制之一。     

Augmented reduction of islet β‐cell mass in Goto‐Kakizaki rats fed high‐fat diet and its suppression by pitavastatin treatment

Aims/Introduction: High fat diet (HFD) is known to be a risk for development of type 2 diabetes. It is unclear, however, how it affects the glucose tolerance or the islet structure in type 2 diabetes. The aim of this study is: (i) to examine the effects of HFD on the islet in GK rats, non‐obese type 2 diabetic model; and (ii) to explore if pitavastatin treatment influences the change. Materials and Methods: To see the effects of HFD on islet changes in type 2 diabetes, 4‐week old male GK and Wistar rats were fed HFD for 16 weeks and subjected to glucose tolerance tests and pathological studies of the islet. The effects of pitavastatin (3 mg/kg/day for 16 weeks, oral), one of the lipophilc statins, were also examined in both GK and Wistrar rats fed with or without HFD. Results: The HFD induced hyperlipidemia and aggravated glucose intolerance in both GK and Wistar rats. Pitavastatin treatment did not influence the glucose tolerance in HFD‐fed animals. HFD caused an increase in hepatic lipid contents in all the animals, which was partially suppressed by pitavastatin treatment. GK rats showed reduced β‐cell mass, and fibrosis and macrophage migration in the islets. HFD feeding in GK rats augmented these changes which were associated with enhanced expression of 8‐hydroxydeoxyguanosine and an increase in apoptotic cells. Pitavastatin treatment improved the HFD‐induced islet pathology, and pancreatic insulin contents paralleled the structural changes. Conclusions: HFD feeding worsened the islet pathology in GK rats which was suppressed by pitavastatin treatment. (J Diabetes Invest, doi: 10.1111/j.2040‐1124.2011.00173.x, 2011)     

Melatonin prevents obesity through modulation of gut microbiota in mice

Excess weight and obesity are severe public health threats worldwide. Recent evidence demonstrates that gut microbiota dysbiosis contributes to obesity and its comorbidities. The body weight‐reducing and energy balancing effects of melatonin have been reported in several studies, but to date, no investigations toward examining whether the beneficial effects of melatonin are associated with gut microbiota have been carried out. In this study, we show that melatonin reduces body weight, liver steatosis, and low‐grade inflammation as well as improving insulin resistance in high fat diet (HFD)‐fed mice. High‐throughput pyrosequencing of the 16S rRNA demonstrated that melatonin treatment significantly changed the composition of the gut microbiota in mice fed an HFD. The richness and diversity of gut microbiota were notably decreased by melatonin. HFD feeding altered 69 operational taxonomic units (OTUs) compare with a normal chow diet (NCD) group, and melatonin supplementation reversed 14 OTUs to the same configuration than those present in the NCD group, thereby impacting various functions, in particular through its ability to decrease the Firmicutes‐to‐Bacteroidetes ratio and increase the abundance of mucin‐degrading bacteria Akkermansia, which is associated with healthy mucosa. Taken together, our results suggest that melatonin may be used as a probiotic agent to reverse HFD‐induced gut microbiota dysbiosis and help us to gain a better understanding of the mechanisms governing the various melatonin beneficial effects.     

A recombinant probiotic for treatment and prevention of cholera

BACKGROUND & AIMS: We have developed a therapeutic strategy based on molecular mimicry of host receptors for bacterial toxins on the surface of harmless gut bacteria. In the present study, this has been applied to the development of a recombinant probiotic for treatment and prevention of cholera, caused by Vibrio cholerae. METHODS: We expressed glycosyltransferase genes from Neisseria gonorrhoeae and Campylobacter jejuni in a harmless Escherichia coli strain, resulting in production of a chimeric lipopolysaccharide terminating in a mimic of the ganglioside GM(1). RESULTS: The recombinant bacterium was capable of binding cholera toxin, a sine qua non of virulence, with high avidity; when tested with purified cholera toxin, it was capable of adsorbing >5% of its own weight of toxin in vitro. Administration of the GM(1)-expressing probiotic also protected infant mice against challenge with virulent V cholerae, even when treatment was delayed until after establishment of infection. When treatment commenced 1 hour after challenge, 12 of 12 mice given the probiotic survived, compared with only 1 of 12 for control mice (P < .00001). CONCLUSIONS: Toxin-binding probiotics such as that described here have considerable potential for prophylaxis and treatment of cholera in humans.     

Visceral hyperalgesia and intestinal dysmotility in a mouse model of postinfective gut dysfunction

BACKGROUND & AIMS: We established the concept that transient enteric infection may lead to persistent gut dysfunction, evident in vitro, in nematode-infected mice. The present study determined whether gut dysfunction in this model involves motor and sensory changes reminiscent of changes found in patients with postinfective irritable bowel syndrome (PI-IBS) and investigated underlying mechanisms. METHODS: Mice infected up to 70 days previously with Trichinella spiralis (Tsp) underwent videofluoroscopy with image analysis to assess upper gastrointestinal motility. Pseudoaffective responses to colorectal distention (CRD) were assessed using a barostat and validated by single fiber recordings from spinal nerves during CRD. Tissues were examined at different time points for histology, immunohistochemistry, and cytokine analysis. Some mice received dexamethasone intraperitoneally on days 23-25 PI or Tsp antigen orally on days 29, 43, and 57 PI. RESULTS: From day 28 PI, no discernible inflammation was present in the gut. Frequency and propagation velocity of intestinal contractions decreased, and retroperistalsis increased at days 28 to 42 PI. CRD induced an allodynic and hyperalgesic response in PI mice, which was accompanied by increased single unit discharge. Gavage of Tsp antigen induced T-cell responses and sustained gut dysfunction for 70 days PI. Administration of dexamethasone postinfection normalized dysmotility and visceral hyperalgesia. CONCLUSIONS: Long-lasting gut dysmotility and hyperalgesia develop in mice after transient intestinal inflammation. These changes are maintained by luminal exposure to antigen and reversed by corticosteroid treatment. The findings prompt consideration of this as a model of PI-IBS.     

Lactobacillus reuteri and Escherichia coli in the human gut microbiota may predict weight gain associated with vancomycin treatment

Background:

Antibiotics, used for 60 years to promote weight gain in animals, have been linked to obesity in adults and in children when administered during early infancy. Lactobacillus reuteri has been linked to obesity and weight gain in children affected with Kwashiorkor using ready-to-use therapeutic food. In contrast, Escherichia coli has been linked with the absence of obesity. Both of these bacteria are resistant to vancomycin.

Objectives and methods:

We assessed vancomycin-associated weight and gut microbiota changes, and tested whether bacterial species previously linked with body mass index (BMI) predict weight gain at 1 year. All endocarditis patients treated with vancomycin or amoxicillin in our center were included from January 2008 to December 2010. Bacteroidetes, Firmicutes, Lactobacillus and Methanobrevibacter smithii were quantified using real-time PCR on samples obtained during the 4–6 weeks antibiotic regimen. L. reuteri, L. plantarum, L. rhamnosus, Bifidobacterium animalis and E. coli were quantified on stool samples obtained during the first week of antibiotics.

Results:

Of the193 patients included in the study, 102 were treated with vancomycin and 91 with amoxicillin. Vancomycin was associated with a 10% BMI increase (odds ratio (OR) 14.1; 95% confidence interval (CI; 1.03–194); P=0.047) and acquired obesity (4/41 versus 0/56, P=0.01). In patients treated with vancomycin, Firmicutes, Bacteroidetes and Lactobacillus increased, whereas M. smithii decreased (P<0.05). The absence of E. coli was an independent predictor of weight gain (OR=10.7; 95% CI (1.4–82.0); P=0.02). Strikingly, a patient with an 18% BMI increase showed a dramatic increase of L. reuteri but no increase of E. coli.

Conclusion:

The acquired obesity observed in patients treated with vancomycin may be related to a modulation of the gut microbiota rather than a direct antibiotic effect. L. reuteri, which is resistant to vancomycin and produces broad bacteriocins, may have an instrumental role in this effect.     

Administration of insulin-like growth factor-I (IGF-I) peptides for three days stimulates proliferation of the small intestinal epithelium in rats.

It has previously been shown that longterm administration of insulin-like growth factor-I (IGF-I) or the analogue Long R3 IGF-I (LR3IGF-I) selectively stimulate growth of the gastrointestinal tract in gut resected, dexamethasone treated, and normal rats. In this study, the short-term effects of IGF-I administration on intestinal proliferation have been investigated. Female rats (110 g, five-six/group) were infused for three days with 2.5 mg/kg/day of either IGF-I or LR3IGF-I and compared with vehicle treated or untreated control rats. LR3IGF-I but not IGF-I increased body weight and wet tissue weight of the small and large intestine (+20%), compared with controls. Tissue weight responses were independent of food intake and were reflected in the histology of the tissue. In LR3IGF-I treated animals, duodenal and ileal crypts length were increased by 13 and 22%, respectively, associated with an increase in crypt cell number. No such histological changes were seen in IGF-I treated rats. Tritiated thymidine labelling indices were significantly increased after administration of either IGF-I or LR3IGF-I (up to 14%) in both the duodenum and ileum. In IGF-I treated rats, increased nuclear labelling was not associated with an increase in the crypt compartment. In contrast, LR3IGF-I induced proportional increments in thymidine labelling and crypt size, suggesting that LR3IGF-I is not only more potent than the native peptide but also induced proliferative events more rapidly. In the colon, the thymidine labelling index was low, however, a non-significant increase in the number of cells labelled with thymidine was seen. These results suggest that within a three day treatment period intestinal mitogenesis is more advanced in animals treated with LR3IGF-I. The differences in proliferative response between the two peptides may be accounted for by variations in pharmacokinetics, clearance rates, and interactions with circulating and tissue specific binding proteins.     

Effect of chromium on carbohydrate and lipid metabolism in a rat model of type 2 diabetes mellitus: the fat-fed, streptozotocin-treated rat

Chromium supplements are widely used as an alternative remedy for type 2 diabetes mellitus (T2DM). In vitro study findings show that chromium picolinate (CrPic) may improve insulin sensitivity by enhancing intracellular insulin receptor. In this study, we evaluated the metabolic effects of CrPic in a rat model of T2DM. Male Sprague-Dawley rats (n = 45, 8 weeks old) were divided into 3 groups. The controls (group I) received a standard diet (12% of calories as fat); group II received a high-fat diet (HFD; 40% of calories as fat) for 2 weeks and then were intraperitoneally injected with streptozotocin (STZ, 40 mg/kg; HFD/STZ) on day 14; group III rats were given group II diets with the addition of 80 microg CrPic per kilogram body weight per day. The addition of CrPic in the group III treatment lowered glucose by an average of 63% (P < .001), total cholesterol by 9.7% (P < .001), and triglycerides by 6.6% (P < .001) compared with group II treatment. Compared with group II, CrPic treatment also lowered free fatty acid levels by 24% (P < .001), blood urea by 33% (P < .05), and creatinine level by 25% (P < .01), and reduced the severity of glomerular sclerosis (P < .0001). Histopathologic findings suggest that the CrPic-treated group had normal renal tubular appearance compared with the HFD/STZ-treated group. Normal appearance of hepatocytes was observed in the CrPic-treated group. These results showed that CrPic has marked beneficial effects against microvascular complications. In conclusion, HFD/STZ rats provide a novel animal model for T2DM. Further treatment with CrPic for 10 weeks significantly ameliorated changes in metabolic risk factors including favorable changes in histopathology of the liver, kidney, and pancreas, suggesting its potential role in the management of diabetes.     

Single-species versus dual-species probiotic supplementation as an emerging therapeutic strategy for obesity

Background and aim

Recent studies have reported beneficial effects of specific probiotics on obesity. However, the difference in the anti-obesity effects of probiotics as single species and dual species is still uncertain. Therefore, we aimed to compare the efficacy of single and dual species of bacteria on markers of obesity in high-fat diet-induced obese rats.

Garcinia Cambogia attenuates diet-induced adiposity but exacerbates hepatic collagen accumulation and inflammation

AIM: To investigate long-term effects of Garcinia Cambogia (GC), weight-loss supplement, on adiposity and non-alcoholic fatty liver disease in obese mice. METHODS: Obesity-prone C57BL/6J mice were fed a high-fat diet (HFD, 45 kcal% fat) with or without GC (1%, w/w) for 16 wk. The HFD contained 45 kcal% fat, 20 kcal% protein and 35 kcal% carbohydrate. They were given free access to food and distilled water, and food consumption and body weight were measured daily and weekly, respectively. Data were expressed as the mean ± SE. Statistical analyses were performed using the statistical package for the social science software program. Student’s t test was used to assess the differences between the groups. Statistical significance was considered at P < 0.05. RESULTS: There were no significant changes in body weight and food intake between the groups. However, the supplementation of GC significantly lowered visceral fat accumulation and adipocyte size via inhibition of fatty acid synthase activity and its mRNA expression in visceral adipose tissue, along with enhanced enzymatic activity and gene expression involved in adipose fatty acid β-oxidation. Moreover, GC supplementation resulted in significant reductions in glucose intolerance and the plasma resistin level in the HFD-fed mice. However, we first demonstrated that it increased hepatic collagen accumulation, lipid peroxidation and mRNA levels of genes related to oxidative stress (superoxide dismutase and glutathione peroxidase) and inflammatory responses (tumor necrosis factor-α and monocyte chemoattractant protein-1) as well as plasma alanine transaminase and aspartate transaminase levels, although HFD-induced hepatic steatosis was not altered. CONCLUSION: GC protects against HFD-induced obesity by modulating adipose fatty acid synthesis and β-oxidation but induces hepatic fibrosis, inflammation and oxidative stress.     

A high-fat diet induces bone loss in mice lacking the Alox5 gene

5-Lipoxygenase catalyzes leukotriene generation from arachidonic acid. The gene that encodes 5-lipoxygenase, Alox5, has been identified in genome-wide association and mouse Quantitative Trait Locus studies as a candidate gene for obesity and low bone mass. Thus, we tested the hypothesis that Alox5(-/-) mice would exhibit metabolic and skeletal changes when challenged by a high-fat diet (HFD). On a regular diet, Alox5(-/-) mice did not differ in total body weight, percent fat mass, or bone mineral density compared with wild-type (WT) controls (P < 0.05). However, when placed on a HFD, Alox5(-/-) gained more fat mass and lost greater areal bone mass vs. WT (P < 0.05). Microarchitectural analyses revealed that on a HFD, WT showed increases in cortical area (P < 0.01) and trabecular thickness (P < 0.01), whereas Alox5(-/-) showed no change in cortical parameters but a decrease in trabecular number (P < 0.05) and bone volume fraction compared with WT controls (P < 0.05). By histomorphometry, a HFD did not change bone formation rates of either strain but produced an increase in osteoclast number per bone perimeter in Alox5(-/-) mice (P < 0.03). In vitro, osteoclastogenesis of marrow stromal cells was enhanced in mutant but not WT mice fed a HFD. Gene expression for Rankl, Pparg, and Cox-2 was greater in the femur of Alox5(-/-) than WT mice on a HFD (P < 0.01), but these increases were suppressed in the Alox5(-/-) mice after 8 wk of treatment with celecoxib, a cyclooxygenase-2 inhibitor. In sum, there is a strong gene by environmental interaction for bone mass when mice lacking the Alox5 gene are fed a HFD.     

Insulin-like growth factor-I and its N-terminal modified analogues induce marked gut growth in dexamethasone-treated rats.

The effects of insulin-like growth factor-I (IGF-I) on the gut of 150 g dexamethasone-treated rats were compared with those of two analogues with reduced affinity for IGF-binding proteins, des(1-3)IGF-I and LR3IGF-I, an N-terminal-extended variant. Administration of IGF-I for 7 days to rats made catabolic by co-treatment with dexamethasone induced a dose-dependent increase in total gut weight, with the highest dose of IGF-I (695 micrograms/day) increasing gut weight by up to 60%, and gut weight as a fraction of body weight by up to 32%. Effects were apparent in all regions of the gut examined, including the stomach, small intestine and colon. Histological and biochemical analyses of the intestine showed that cross-sectional mass, rather than gut length, was increased, and proportional increases in wet weight, protein and DNA content per unit length were measured in both the mucosa and muscularis layers. The rate of duodenal protein synthesis measured on day 7 of treatment was not increased by IGF-I treatment. The IGF-I analogues had qualitatively similar effects to IGF-I, but were consistently severalfold more potent, providing evidence that IGF-binding proteins reduce the biological activity of exogenous IGF-I in the gut. The results indicate that the gut is one of the most sensitive IGF-I target tissues, and that potency in vivo correlates with a reduced interaction with IGF-binding proteins.     

罗格列酮对胰岛素抵抗大鼠血小板CD40配体的作用

目的 观察罗格列酮对胰岛素抵抗大鼠血小板CD40配体(CD40L)变化的影响,进一步明确胰岛素抵抗、CD40L之间的关系. 方法 健康SD大鼠60只,随机分为普食组、高脂组、小剂量干预组和大剂量干预组.普食组给予基础饲料,高脂组、小剂量干预组、大剂量干预组均给予高脂饲料.喂养12周后小剂量干预组每天给予5 mg/kg罗格列酮灌胃,大剂量干预组每天给予10mg/kg罗格列酮灌胃,高脂组、普食组则给予相应剂量的生理盐水灌胃.干预治疗4周后(第16周)用稳态模型评估法计算胰岛素抵抗指数(HOMA-IR),以ELISA法测定循环sCD40L浓度,以免疫沉淀、免疫印迹测定血小板膜蛋白CD40L表达. 结果 高脂组与普食组比较,HOMA-IR(9.8±3.2比5.9±1.7)、循环sCD40L(367.3±35.3比232.3±120.6)、血小板CD40L(2.1±0.4比1.4±0.2)均明显升高(均为P<0.05).罗格列酮干预后,大剂景组HOMA(5.4±1.1)、循环sCD40L(276.9±54.0)、血小板CD40L(1.4±0.3)均明显降低(均为P<0.05). 结论 胰岛素抵抗大鼠血小板CD40L表达升高;大剂最罗格列酮干预后,CD40L随着胰岛素抵抗的改善而下降.     

Helicobacter species and common gut bacterial DNA in gallbladder with cholecystitis

AIM:To analyze the association between Helicobacter spp. and some common gut bacteria in patients with cholecystitis. METHODS:A nested-polymerase chain reaction (PCR), specif ic to 16S rRNA of Helicobacter spp. was performed on paraff in-embedded gallbladder samples of 100 cholecystitis and 102 control cases. The samples were also analyzed for some common gut bacteria by PCR. Positive samples were sequenced for species identif ication. RESULTS: Helicobacter DNA was found in seven out of 100 cases of acute a...     

Efficacy profiles for different concentrations of Lactobacillus acidophilus in experimental colitis

AIM:To determine the efficacy profiles of different concentrations of Lactobacillus acidophilus(L.acidophilus)for treating colitis using an experimental murine model.METHODS:Colitis was established in 64 BALB/c mice by adding 5%dextran sodium sulfate(DSS)to the drinking water and allowing ad libitum access for 7 d.The mice were then randomly divided into the following control and experimental model groups(n=8 each;day 0):untreated model control;negative-treatment model control(administered gavage of 1 mL/10 g normal saline);experimental-treatment models C4-C8(administered gavage of 104,105,106,107,or 108CFU/10 g L.acidophilus,respectively);positive-treatment model control(administration of the anti-inflammatory agent prednisone acetate at 45 g/10 g).Eight mice given regular water(no DSS)and no subsequent treatments served as the normal control group.Body weight,fecal traits,and presence of fecal occult blood were assessed daily.All animals were sacrificed on post-treatment day7 to measure colonic length,perform histological scoring,and quantify the major bacteria in the proximal and distal colon.Intergroup differences were determined by one-way ANOVA and post-hoc Student-Newman-Keuls comparison.RESULTS:All treatments(L.acidophilus and prednisone acetate)protected against colitis-induced weight loss(P<0.05 vs model and normal control groups).The extent of colitis-induced colonic shortening was significantly reduced by all treatments(prednisone acetate>C4>C5>C7>C8>C6;P<0.05 vs untreated model group),and the C6 group showed colonic length similar to that of the normal control group(P>0.05).The C6 group also had the lowest disease activity index scores among the model groups.The bacterial profiles in the proximal colon were similar between all of the experimental-treatment model groups(all P>0.05).In contrast,the bacterial profile in the distal colon of the C6 group showed the distinctive features(P<0.05 vs all other experimental-treatment model groups)of Lactobacillus sp.and Bifidobact     

Effects of Lactobacillus plantarum on gut barrier function in experimental obstructive jaundice

AIM: To investigate the mechanisms of Lactobacillus plantarum (L. plantarum) action on gut barrier in preoperative and postoperative experimental obstructive jaundice in rats.METHODS: Forty rats were randomly divided into groups of sham-operation, bile duct ligation (BDL), BDL + L. plantarum, BDL + internal biliary drainage (IBD), and BDL + IBD + L. plantarum. Ten days after L. plantarum administration, blood and ileal samples were collected from the rats for morphological examination, and intestinal barrier function, liver function, intestinal oxidative stress and protein kinase C (PKC) activity measurement. The distribution and expression of the PKC and tight junction (TJ) proteins, such as occludin, zonula occludens-1, claudin-1, claudin-4, junction adhesion molecule-A and F-actin, were examined by confocal laser scanning microscopy, immunohistochemistry, Western blotting, real-time fluorescent quantitative polymerase chain reaction assay.RESULTS: L. plantarum administration substantially restored gut barrier, decreased enterocyte apoptosis, improved intestinal oxidative stress, promoted the activity and expression of protein kinase (BDL vs BDL + L. plantarum, 0.295 ± 0.007 vs 0.349 ± 0.003, P < 0.05; BDL + IBD vs BDL + IBD + L. plantarum, 0.407 ± 0.046 vs 0.465 ± 0.135, P < 0.05), and particularly enhanced the expression and phosphorylation of TJ proteins in the experimental obstructive jaundice (BDL vs BDL + L. plantarum, 0.266 ± 0.118 vs 0.326 ± 0.009, P < 0.05). The protective effect of L. plantarum was more prominent after internal biliary drainage ( BDL + IBD vs BDL + IBD + L. plantarum, 0.415 ± 0.105 vs 0.494 ± 0.145, P < 0.05).CONCLUSION: L. plantarum can decrease intestinal epithelial cell apoptosis, reduce oxidative stress, and prevent TJ disruption in biliary obstruction by activating the PKC pathway.     

Helianthus tuberosus(Jerusalem artichoke) tubers improve glucose tolerance and hepatic lipid profile in rats fed a high-fat diet

Objective:To analyze the effects of feeding Helianthus tuberosus(HT) tubers on glucose tolerance and lipid profile in rats fed a high-fat diet(HFD). Methods:A normal HFD or HFD including 10 w/w% HT tubers(HFD + HT) was fed to F334/Jcl rats. After 10 weeks,organ weights,glucose tolerance,and lipid profile were analyzed. Results:The body weight,liver weight,and epidermal fat content in the HFD group were higher than those of the normal group,and similar to those of the HFD + HT group. The oral glucose tolerance test at 10 weeks revealed that the blood glucose level 30 minutes after beginning the test in the HFD + HT group was significantly lower than that in the HFD group. Liver triglyceride and total cholesterol levels in the HFD + HT group were significantly lower than those in the HFD group. Fecal triglyceride and total cholesterol levels in the HFD + HT group were higher than those in the HFD group. Histological analyses revealed that fat and glycogen accumulation increased in the HFD group,but decreased in the HFD + HT group. Conclusions:These results indicate that HT tubers have anti-fatty liver effects based on improvements in glucose tolerance and the hepatic lipid profile.     

运动对高脂饮食诱导肥胖大鼠过氧化物酶体增长因子活化受体-δ表达和胰岛素抵抗的影响

研究运动对高脂饮食诱导的肥胖大鼠肌肉和脂肪组织中过氧化物酶体增长因子活化受体-δ（PPAR-δ）表达的影响,并探讨其改善胰岛素抵抗的可能机制.方法 取体质量135～150 g的9周龄雄性Wistar大鼠80只,随机数字表法取其中60只6周时间饲以高脂饲料用于制作肥胖大鼠模型,另20只饲以普通饲料.将54只造模成功肥胖大鼠随机分为高脂饮食组（HFD）、高脂饮食同时运动组（E-HFD）、高脂饮食后运动组（HFD-E）,每组18只,同时从普通饲料饲养大鼠中随机选择16只作为正常饮食组（RD）.按文献标准对各组大鼠进行6周运动训练.检测比较各组游泳运动训练后体质量、肿瘤坏死因子（TNF）-α、瘦素、白细胞介素（IL）-1的水平以及空腹血糖、空腹胰岛素并计算胰岛素敏感指数（ISI）,采用实时定量聚合酶链反应（RT-PCR）检测肌肉和脂肪组织中PPAR-δ、葡萄糖转运蛋白（GLUT）-4、磷酸肌醇3激酶（PI3K）mRNA的表达,并采用Western blot法检测肌肉和脂肪组织中PPAR-δ蛋白的表达水平.组间数据比较采用双侧t检验.结果 HFD组ISI为1.13±0.21,相比HFD组,E-HFD组和HFD-E组的IS1分别提高了 71.1%和45.7%（分别为2.09±0.32和1.80±0.34）,而HFD-E组低于E-HFD组,差异均有统计学意义（均P＜0.05）.HFD组TNF-α水平为（101±24）ng/L,相比HFD组,E-HFD组和HFD-E组则分别下降了20.0%和9.2%[分别为（81±16）和（92±19）ng/L],差异均有统计学意义（P＜0.05）.与HFD组相比,E-HFD组和HFD-E组瘦素和IL-I水平均有显著下降（均P＜0.05）.与HFD组相比,E-HFD组和HFD-E组骨骼肌和脂肪中PPAR-δ、GLUT-4、PI3K mRNA的表达均显著升高,差异均有统计学意义（均P＜0.05）,且在E-HFD组变化尤为显著（均P＜0.01）.与HFD组相比,E-HFD组骨骼肌和脂肪组织中PPAR-δ蛋白表达分别升高了388.4%和203.2%（均P＜0.05）;HFD-E组骨骼肌和脂肪组织中PPAR-δ蛋白的表达则分别升高了272.9%和117.9%（均P＜0.05）.结论 运动降低了高脂饮食诱导的肥胖大鼠的血清脂肪因子瘦素、TNF-α和IL-1水平,改善了胰岛素抵抗,可能是通过上调肌肉和脂肪组织中PPAR-δ的表达发挥作用.     

重组人脑利钠肽对大鼠心肌梗死后心室重构及功能的影响

目的 探讨重组人脑利钠肽(rhBNP)对心肌梗死后大鼠心室重构及心功能的影响.方法 建立急性心肌梗死(AMI)雄性SD大鼠模型45只,随机分为AMI对照组、小剂量rhBNP治疗组、大剂最rhBNP治疗组,每组各15只.另设15只作假手术组.rhBNP治疗组经颈静脉输液管输注rhBNP,剂量分别为5μg/ks和15 μg/kg,1次/d,持续4周,假手术组及AMI对照组仅以等体积的生理盐水输注.4周后检测血液动力学及心功能参数,心脏标本检测左室重量及左室重量指数(LVMI)、心肌梗死面积,并检测血浆和心肌血管紧张素Ⅱ(Ang Ⅱ)水平.结果 AMI对照组左室重量、LVMI及心肌AngⅡ水平明显高于假手术组,而收缩压及左室内压最大上升和下降速率(±dp/dt)均明显低于假手术组(均P<0.01).大、小剂量rhBNP治疗组左室重量及LVMI、心肌梗死面积和心肌AngⅡ水平均明显低于AMI对照组[左室重量:分别为(492.6±34.0)mg、(498.8±47.8)mg比(570.0±24.2)mg,P<0.01;LVMI:2.0±0.2、2 0±0.2比2.3±0.1,P<0.01;心肌梗死面积:(25.3±2.9)%、(31.4±3.0)%比(46.4±3.0)%,P<0.01;Ang Ⅱ水平:(881.3±62.7)pg/L、(1186.0±94.5)pg/L比(2436.7±280.3)pg/L,P<0.05],收缩压和±dp/dt也高于AMI对照组(P<0.01或P<0.05).结论 外源性的rhBNP连续应用能限制梗死面积、减轻AMI后心室重构、保护心功能.