Age-related decrease in aromatase and estrogen receptor （ERα and ERβ） expression in rat testes： protective effect of low caloric diets

Aim： To examine the effects on rat aging of caloric restriction （CR1） and undernutrition （CR2） on the body and on testicular weights, on two enzymatic antioxidants （superoxide dismutase and catalase）, on lipid peroxidation and on the expression of testicular aromatase and estrogen receptors （ER）. Methods： CR was initiated in 1-month-old rats and carried on until the age of 18 months. Results： In control and CR2 rats an age-related decrease of the aromatase and of ER （α and β） gene expression was observed; in parallel a diminution of testicular weights, and of the total number and motility of epididymal spermatozo was recorded. In addition, aging in control and CR2 rats was accompartied by a significant decrease in testicular superoxide dismutase, catalase activities, and an increase in lipid peroxidation level （thiobarbituric acid reactive substance）, associated with alterations of spermatogenesis. Conversely, caloric restriction-treatment exerted a protective effect and all the parameters were less affected by aging. Conclusion： These results indicate that during aging, a low caloric diet （not undernutrition） is beneficial for spermatogenesis and likely improves the protection of the cells via an increase of the cellular antioxidant defense system in which aromatase/ ER could play a role. （Asian J Andro12008 Mar; 10： 177-187）

Effect of Starvation-Refeeding Status on Cholesterol Metabolism in Rats Fed High-Cholesterol Diet

The present study investigated the effect of starvation-refeeding status on cholesterol metabolism in rats fed a high-cholesterol diet or a cholesterol-free diet. Twenty male and 20 female Donryu rats (age 5 weeks) were fed a cho-lesterol-free diet for 14 days. Then the male and female rats were each divided into two groups: feeding and starva-tion-refeeding groups. The feeding groups were fed the experimental diet for 3 days, and the starvation-refeeding groups fasted for 2 days followed by 3 days of feeding. Half of each of groups was fed a cholesterol-free diet and the other half was fed a high-cholesterol diet. Starvation-refeeding significantly increased the plasma free cholesterol and HDL-cholesterol concentrations in both the high-cholesterol-diet-fed rats and the cholesterol-free-diet-fed rats. In the female rats, plasma total cholesterol and cholesteryl ester concentrations were significantly higher in the high-cholesterol groups than in the cholesterol-free groups, whereas TG concentration and total cholesterol/TG ratio were not significantly different among all of the groups. Liver total cholesterol and cholesteryl ester were significantly higher in the high-cholesterol groups than in the cholesterol-free groups in both male and female rats. These results suggest that starvation-refeeding affected cholesterol metabolism at least in part. The reactivity of the cholesterol me-tabolism may be different between male and female rats.

Age-Related Biomarkers Can be Modulated by Diet in the Rat

This study seeks to establish the normal serum concentrations of biochemical markers related to nutrition, inflammation and disease, and to investigate how the levels change with age and diet in the rat. To this end, we fed rats from weaning on three diets differing in their protein, carbohydrate and fatty acid content. The diets consisted of a control, nutritionally balanced diet, this same diet supplemented with 10% (wt/wt) beef tallow, and a diet that was high in fat and carbohydrate and low in protein. Blood samples from rats at two different ages, 3 months and 12 months, were then analysed. In control rats, with advancing age there was a general decrease in potassium, iron and serum albumin concentrations and in the activities of aspartate aminotransferase and alanine aminotransferase, and an increase in total and HDL cholesterol. These changes were modulated by diet: many of the age-related changes (serum concentrations of potassium, iron and cholesterol, and liver enzyme activities) were not observed in animals eating the high fat diet. In contrast, the high carbohydrate, high fat, low protein diet-fed animals showed several additional changes (serum concentrations of sodium, urea, creatinine and TG, and activity of alkaline phosphatase) that can be related to kidney, liver and cardiovascular health.

Effects of a Regional Chinese Diet and Its Vitamin Supplementation on Proliferation of Human Esophageal Cancer Cell Lines

Objective To study the effects of a local diet popular in Yanling region （YT diet） on the proliferation of two human cell lines （Eca-109 esophageal squamous cell carcinoma line and HL7702 normal liver epithelial cell line） in rats by a sero-physiological approach. Methods Male SD rats were divided into six groups and fed respectively with a conventional diet and the YT diet （one of the five experimental diets） supplemented with two vitamin mixtures （Mix.1： vitamins A, E, and folic acid; Mix.2：mix.1 plus riboflavin and vitamin C） at two different doses. On the 30th day, sera were collected from the rats and added into a medium for cell culture, with 10% FBS used as a serum control. The effects were assessed by MTT assay, DNA synthesis and flow cytometry assays. Results Compared with the control, the sera from rats fed with the YT diet significantly promoted the proliferation of Eca-109 cells, which was, however, reversed by the supplementation with two vitamin mixtures at high doses. Surprisingly, the same treatment produced contrary effects on HL7702 cells as compared with Eca-109 cells. Conclusion The sera from rats fed with the YT diet could promote the proliferation of human esophageal cancer cell line Eca-109, whereas the sera from those fed with the YT diet supplemented with vitamin mixtures might have inhibitory effects on the proliferation of Eca-109 ceils.

Comparative study on the difference of obesity model induced by two kinds of high fat diet in Sprague-Dawley rats

Objective: To explore the differences of obese Sprague-Dawley(SD)rats model induced by lard oil high-fat(HF)diet or purified HF diet. Methods: SD weanling rats were randomly divided into three groups: D1 group,where rats were fed by lard oil HF diet;D2 group,where rats were fed by purified HF diet;C group,where rats were fed on chow. After 12 weeks,diet-induced obesity rat(stop 33% based on weight)were selected for further study,and the rest rats from group D1 and D2 were excluded. The food intake and weight were weighted daily and weekly,respectively. The subcutaneous,visceral and total fat contents of rats was measured by 256-row CT scan and the Lee index was calculated accordingly. The kidney,liver,testis,spleen and heart were weighted respectively. Serum leptin and insulin levels were quantified. The pathology in liver and adipose tissues were analyzed by HE staining. Oral glucose tolerance test(OGTT)was used to compare the glucose tolerance ability. Serum total cholestero(lT-CHO),high density lipoprotein(HDL-C),low density lipoprotein(LDL-C),triglyceride(TG)and inflammatory cytokines IL-6,TNF-α were detected as well. Results: After 12 weeks,the body weight,subcutaneous fat,visceral fat,total fat mass,wet weight of liver,kidney and heart,area under blood glucose curve and the levels of serum insulin,leptin,T-CHO,LDL-C,TG,IL-6 and TNF-α in group D2 were significantly increased compared to those of group C and group D1. HDL-C of group D2 was markedly lower than that in group C(P<0. 05). The visceral fat,total fat content and HDL-C in group D1 were significantly different from those of group C(P<0. 05). Steatosis and enlarged adipocyte were found in the livers of rats in group D1 and D2,and the lesions were more significant in group D2. Conclusion: Purified HF diet was more effective in inducing metabolic abnormalities,steatosis,peripheral chronic inflammation in obese SD rat models. But lard oil HF diet was more economical when only inducing visceral steatosis was required.

Elevated glucagon-like peptide-1 on a high-fat diet feeding prevents the incidence of diabetes mellitus in Spontaneously Diabetic Torii <i>Lepr^fa</i>rats

Nutritional regulation plays a critical role to reduce the incidence or progression of diabetes mellitus. In this study, we investigated the effects of a high-fat diet on Spontaneously Diabetic Torii Leprfa (SDT fatty) rats, a novel model for obese type 2 diabetes. The SDT fatty rats were divided into two dietary groups, which were fed a high-fat diet or a standard diet for 18 weeks, from 6 to 24 weeks of age. The calorie intake in the high-fat diet (HF) group was reduced after 10 weeks of age and the group inhibited an incidence of diabetes. Interestingly, the HF induced an increase of serum glucagon-like peptide-1 (GLP-1) levels in SDT fatty rats with refeeding. Fat tissue weights in the HF group increased, but the visceral fat/subcutaneous fat (V/S) ratio decreased. Moreover, histopathological observations revealed an improvement of the pancreatic abnormalities and fatty liver in the HF group. In conclusion, a preventive effect on diabetes in rats fed a high-fat diet has a relation with an increase in incretin hormone, and it might be advantageous for prevention of incidence or progression of diabetes to develop functional foods inducing an increase in incretin hormone.

Soybean Flour Improves Fatty Acid Profile and Decreases Hepatic Triglyceride Deposition in Rats Fed with Normocaloric and Hypercaloric Diet

This study investigated the effects of replacing casein with soy flour on the fatty acids profile and triglycerides metabolism in the liver of rats that were previously fed with normocaloric and hypercaloric diets based on casein. Wistar male rats were used;one group was fed with control diet (AIN-93) and another with hypercaloric diet (AIN-93 with 34.15% sucrose, 42% fat calories) for 9 weeks. Each group was then divided into two subgroups and casein was replaced with soybean in one of them, obtaining CC (control casein), CS (control soy), HC (hypercaloric casein) and HS (hypercaloric soy), which were fed for 6 weeks. We measured triglycerides in serum, and triglycerides, total lipids, fatty acids profile, the expression of apolipoprotein B (Apo B), acetyl-CoA carboxylase (ACC), fatty acid synthase (FAS), sterol-regulatory element-binding protein 1c (SREBP-1c), mitochondrial glycerol-3-phosphate acyltransferase (mGPAT), diacylglycerol acyltransferase 2 (DGAT-2), carnitine palmitoyltransferase 1 (CPT-1) and peroxisome proliferator-activated receptors alpha (PPARα) in liver. Histological studies were also performed. When comparing HS vs. HC, a positive effect of soybean flour on hepatic triglycerides deposits was found, possibly through the reduction in DGAT-2 expression (P < 0.01) and the increase in Apo B (P < 0.001) expression. Soybean flour also decreased fat deposits in control diets when compared with casein, decreasing the DGAT-2 (P < 0.001) expression and increasing Apo B (P < 0.001), CPT-1 (P < 0.05) and PPARα (P < 0.01) expressions. Both soy diet subgroups increased unsaturated fatty acids respect to casein diets (P < 0.01). Hepatocytes showed few lipid droplets in HS, whereas a fat deposit in HC was observed. These results suggest that replacing casein with soybean flour in normocaloric and hypercaloric diets reduces triglycerides and improves fatty acids profile in rat liver.

Apoptosis of Pancreatic Beta Cells in Pregnant Insulin-resistant Rats Fed with High-fat Diet

Objective The aim of this study is by observing the number change of islets beta cells in gestational rats exposed to high fat diet, tofurther reveal the mechanism of gestational diabetes mellitus. Methods Female Wistar rats were exposed to high fat diet for five weeks, and then became pregnant. During pregnancy dynamically detected indicators of glucose and fat. Until the third trimester of pregnancy evaluated the sensitivity of insulin and glucose tolerance. After executed rats, selected pancreatic tail tissue and fixed, further slides were stained with insulin antibody by immunohistochemistry to confirm the location of beta cells. Image analysis system determined mean area stained positive cells in each islet, which stood for total number of beta cells. The apoptotic beta cells in islet were detected and quantified by the Tunel technology to calculate apoptosis ratio. Results The level of free fatty acids in rats exposed to high fat diet was significantly higher than the control groups, and insulin resistance was more serious. Compared mean stained positive area among each group, the largest was gestational rats fed high fat diet, and gestational rats was larger than virgin rats, but the difference had no statistical significance. About apoptoticratio of beta cells was higher in diet intervened rats, gestational rats were higher than virgin rats. The same trend happened in the number of positive cells, but discrepancy was not remarkable. Conclusion Based on insulin resistance, apoptosis of pancreatic beta cellsincreased in gestational ratstaking high fat diet, through changing the number of beta cells to down regulate the pancreas endocrine function. That may be the mechanism of gestational mellitus.

Effect of Alligator Pepper on Litter Weight of Rats Fed on High Glycemic Index Diet

This study was carried out to find out if alligator pepper can prevent the development of fetal macrosomia in Sprague-Dawley rats fed with high glycemic index diet. Fifteen adult female Sprague-Dawley rats of proven fertility were acclimatized for a period of two weeks in a well-ventilated laboratory and fed with grower’s mash and water ad libitum. Thereafter, they were randomly placed in separate cages after which a male Sprague-Dawley rat of proven fertility was introduced into each of the cages containing the female rats. They were left in the cages for three days during, which mating was confirmed to have occurred. The male rats were then withdrawn from the female rats, which were placed in separate maternity cages. The female rats were randomly allocated to three groups A, B and C so there were 5 pregnant rats in each group. The rats in group A were fed with 50 g of grower’s mash daily while the rats in groups B and C were fed with 50 g of cooked fermented cassava respectively. All rats were given water ad libitum throughout the duration of the experiment. The rats in groups A and B were intraperitoneally injected with 13.3 ml per Kg body weight of distilled water while the rats in group C were intraperitoneally injected with 13.3 mg/Kg body weight of aqueous extract of alligator pepper respectively. They were observed for 18 - 25 days. The litters of the rats in group B had a significantly higher mean weight than the rats in group A while the litters of the rats in group C had a significantly lower mean weight than the rats in groups B. It was concluded that intraperitoneally injected aqueous extract of alligator pepper, in the first trimester of pregnancy, can prevent the development of fetal macrosomia in Sprague-Dawley rats.

Effect of Cholesterol Enriched or Fatty-Acid Diets on Cholesterol and Lipid Levels in Young Wistar Rats

Nutritional intake is a fundamental determinant of health. It is well known that cholesterol rich diets can induce several pathological conditions but detailed mechanism underlying these remains unknown. Wistar rats, an animal strain widely used in the research have been employed to study the effects of dietary interventions due to their metabolic characteristics, which are closer to the human compared to mice. The effect of some components of the western diet, combined with cholesterol in the lipid profile have been studied, but the impact of only cholesterol or fatty-acid diets in such a profile has not been yet characterized. Here we measured the effect of 6 or 16 weeks of dietary intervention with cholesterol enriched diet (CED) or fatty-acid diet (FAD) on cholesterol, triglyceride levels, high density lipoproteins (HDL) and low density lipoproteins (LDL). We observed significant differences in body weight only in animals treated with CED or FAD from Week 9 onwards as compared to animals fed the control diet. There were no differences between animals fed with CED or FAD in cholesterol levels at any time point nevertheless, triglyceride levels were significantly increased as compared to control diet in animals under both diets at early time points. Finally, both CED and FAD induced a decrease in HDL as compared to control levels in treatments of more than 6 weeks, whereas LDL transiently increased in animals treated with FAD from 10 to 12 weeks, but after this period LDL levels returned to baseline, suggesting that young rats have a compensatory effect at least for the period of time analyzed here. Here we provide a temporal course on lipid profile of cholesterol, triglycerides, HDL and LDH in Wistar rats treated with CED and FAD diet that can be useful as reference for future studies.

Effect of mango seed kernel extract on the adipogenesis in 3T3-L1 adipocytes and in rats fed a high fat diet

Mangoes (Mangifera indica L.) are one of the most important tropical foods. The seed is one of the main by-products of mango processing. Therefore, it is important to find an economically viable use for this waste (e.g., as a food additive or supplement with high nutraceutical value). We investigated the anti-obesity effects of mango seed kernel extract with hot water (MSKE-W) in 3T3-L1 adipocytes and in a high fat diet (HFD)-induced obesity rat model. MSKE-W caused a significant decrease in the activity of glycerol 2-phosphate dehydrogenase in 3T3-L1 adipocytes without eliciting cell cytotoxicity and inhibited cellular lipid accumulation through down-regulation of transcription factors such as PPARγ and C/EBPα. In the animal model, rats fed an HFD containing 1% MSKE-W gained less weight than rats fed an HFD alone. The visceral fat mass in rats fed an HFD containing 1% MSKE-W tended to be lower than that in rats fed an HFD alone. Furthermore, histological examination of rat livers from an HFD showed steatohepatitis. However, rats on an HFD containning 1% MSKE-W showed no histopathological changes in liver tissue. Our results indicate that MSKE-W influences anti-obesity effects, both in vitro and in vivo, and suggest that MSKE-W provides a novel preventive potential against obesity.

山西老陈醋通过JAK2/STAT3通路减轻高脂饮食诱导的大鼠肝损伤

旨在探究山西老陈醋通过JAK2/STAT3通路减轻高脂饮食诱导大鼠肝损伤的作用机制。使用高脂乳剂灌胃大鼠5周,构建高脂血症模型;同时低、中、高剂量(按体质量计1.35、2.7、5.4 g/kg)山西老陈醋灌胃大鼠10周。血清学检测血清中总胆固醇(TC)、甘油三酯(TG)、高密度脂蛋白胆固醇(HDL-C)、超氧化物歧化酶(SOD)、谷胱甘肽还原酶(GRx)、总抗氧化能力(T-AOC)、谷草转氨酶(AST)、谷丙转氨酶(ALT)、碱性磷酸酶(ALK-P)水平;HE染色检测肝脏病理学变化;q-PCR和WB检测肝脏中JAK2、STAT3 mRNA和蛋白水平表达;免疫组化技术定位分析。结果显示,不同剂量山西老陈醋均能够极显著降低脂质含量和肝损伤程度,提高抗氧化酶活性,极显著抑制JAK2、STAT3 mRNA和蛋白含量(P<0.01);其中高剂量组TC、TG降低20.50%、48.65%,高、中剂量组对AST(32.79%、29.07%)、ALT(21.65%、20.67%)、ALK-P(19.42%、19.71%)效果最好;与低剂量组相比,高中剂量组JAK2(57.07%、34.02%)、STAT3(55.19%、41.45%)mRNA和JAK2(27.89%、24.09%)、STAT3(33.06%、26.64%)蛋白含量(极)显著降低(P<0.05,P<0.01)。综上,山西老陈醋减轻高脂饮食诱导大鼠的肝损伤的作用,可能是通过抑制JAK2/STAT3通路的活化来实现。

不同高脂饲料配方对建立非酒精性脂肪肝大鼠模型的影响

目的:比较3种不同配方高脂饲料构建非酒精性脂肪肝大鼠模型的差异,提高高脂饲料建立非酒精性脂肪肝大鼠模型的成功率,为非酒精性脂肪肝病的研究提供稳定可靠的动物模型。方法:将SPF级雄性SD大鼠随机分为普通饲料对照组、高脂饲料1组(HFD1组)、高脂饲料2组(HFD2组)、高脂饲料3组(HFD3组)。各组大鼠分别给予相应饲料8周。造模期间记录大鼠一般情况、体质量和摄食量。喂养8周后,采用腹部超声、计算机断层扫描(CT)、核磁共振成像(MRI)对大鼠肝脏进行检查。取血和肝脏,检测肝功能指标(丙氨酸氨基转移酶、天门冬氨酸氨基转移酶)、血脂指标(甘油三酯、总胆固醇、高密度脂蛋白胆固醇、低密度脂蛋白胆固醇)和炎症指标(IL-1β、IL-6、TNF-α)的变化。肉眼观察肝脏大体形态,计算其肝指数和Lee’s指数。比较上述指标在各组间的差异,综合评估不同配方高脂饲料对非酒精性脂肪肝大鼠模型的影响。结果:与对照组大鼠相比,HFD1组、HFD2组、HFD3组大鼠精神变差、活动减少、脱毛现象加重、摄食量减少、体质量明显升高,肝指数、Lee’s指数显著提高,肝脏体积增大,边缘较钝,可见脂肪变性和沉积,且以HFD3组大鼠变化最为明显;HFD1组、HFD2组、HFD3组大鼠血清谷丙转氨酶、天门冬氨酸氨基转移酶、甘油三酯、总胆固醇、低密度脂蛋白胆固醇和IL-1β、IL-6、TNF-α水平均显著升高,高密度脂蛋白胆固醇显著降低,且HFD3组更为明显;HFD1组、HFD2组、HFD3组大鼠肝脏肿大,实质回声增强,肝内管状结构显示欠清,肝和脾的CT值比值明显降低,同/反相位图上肝脏实质信号差别明显,且HFD3组对于大鼠影像学变化影响更大。结论:三种高脂饲料喂养SD大鼠8周后,均可建立非酒精性脂肪肝大鼠模型,但HFD3组诱导非酒精性脂肪肝大鼠模型优于其他两组,病变相对严重,预计维持时间也更长,更适于非酒精性脂肪肝病的机制研究和降脂药物的筛选。

痰热腑实证大鼠模型建立的条件探索

目的设置不同的高脂饮食模式以建立痰热腑实证大鼠模型,探讨不同造模条件对模型质量的影响。方法随机将36只雄性SD大鼠分为A组、B组、C组,每组12只。A组给予普通维持饲料、B组给予高脂饲料、C组给予普通维持饲料+高脂乳剂灌胃,造模周期28 d;于造模的第26天起给予B、C组大鼠自体粪便混悬液灌胃,连续3 d。比较三组大鼠一般指标、舌象指标、粪便指标和血脂水平。结果与A组比较,B、C组大鼠的日均饮食量和饮水量均较少(均P<0.05);B、C组大鼠日均饮食量和饮水量差异均无统计学意义(均P>0.05)。造模第1、2周,三组大鼠体重差异均无统计学意义(均P>0.05);造模第3周,A、B两组大鼠体重均大于C组大鼠(均P<0.05);造模第4周,B组、A组、C组大鼠体重依次降低(均P<0.05)。造模第1周,C组大鼠体温低于A、B组(均P<0.05);造模第2周,B组大鼠体温高于A、C组大鼠;造模第3周,B、C组大鼠体温均高于A组;造模第4周,B组大鼠体温高于A、C组大鼠(均P<0.05)。末次灌胃后,B、C组大鼠舌象R、G、B值均低于A组大鼠,B、C组大鼠舌下脉络评分均高于A组大鼠(均P<0.05)。与A组比较,B、C两组大鼠粪便粒数、粪便湿重、Bristol分级量表(BSFS)评分均减少/降低(均P<0.05);B、C组大鼠粪便粒数、粪便湿重、BSFS评分差异均无统计学意义(均P>0.05)。粪便灌胃后,与A组比较,B组血清总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDL-C)水平均升高(均P<0.05),C组血清TC、LDL-C水平均升高(均P<0.05);B、C组大鼠血清LDL-C、TC、TG、HDL-L水平差异均无统计学意义(均P>0.05)。结论与普通维持饲料+高脂乳剂灌胃+自体粪便混悬液灌胃法相比,高脂饲料喂养+自体粪便混悬液灌胃法造模能复制出体征症候更明显、稳定性更强、齐同性更好的痰热腑实证动物模型。

复方中草药提取物改善高脂饮食诱导的小鼠脂代谢紊乱

研究旨在探究复方中草药方剂中的活性成分对高脂饮食小鼠脂代谢的影响。采用水提醇沉的方法提取复方中草药方剂(柴胡、决明子、泽泻、黄芪、姜黄、陈皮)中的活性成分,并将80只小鼠随机分为对照组(CK组)、高脂日粮组(HFD组)、复方中草药提取物低剂量组(L-CCME组)、复方中草药提取物高剂量组(H-CCME组)4组,试验为期6周。试验期间每周称重;试验结束时采集血清、肝脏和肠道组织,采用试剂盒检测血清三酰甘油(TG)、总胆固醇(TC)、高密度脂蛋白(HDL-C)、低密度脂蛋白(LDL-C)、白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)、谷丙转氨酶(ALT)和谷草转氨酶(AST)含量及肠道中IL-6和TNF-α含量;采用荧光定量PCR和蛋白质免疫印迹检测肝脏脂肪酸合成酶(FAS)和肉碱棕榈酰转移酶-I(CPT-I)表达量。结果表明:与CK组相比,HFD组小鼠血清中ALT、AST、TC和TG含量显著升高(P<0.05),表明造模成功。与HFD组相比,H-CCME组小鼠体重显著降低(P<0.05);试验结束时,与HFD组相比,H-CCME组小鼠TC、TG和LDL-C显著降低,HDL-C显著升高(P<0.05);此外,与HFD组相比,H-CCME组小鼠血清和肠道中IL-6和TNF-α水平显著降低(P<0.05),粪便中脂肪含量升高(P<0.05);与HFD组相比,H-CCME组小鼠肝脏中CPT-I mRNA和蛋白表达水平显著升高,FAS mRNA和蛋白表达水平显著降低(P<0.05)。说明复方中草药提取物能够有效治疗因高脂饲喂导致的脂质代谢异常,且最适添加量为400 mg/kg。

孕前肥胖和孕期过度增重母鼠哺乳期饮食对子鼠炎性指标及铁相关指标的影响

目的探究孕前肥胖和孕期过度增重母鼠哺乳期饮食对子鼠离乳后炎性指标及铁相关指标的影响。方法将24只健康的SPF级Wistar雌性大鼠以1∶1比例随机分为孕前肥胖组和孕期过度增重组,根据哺乳期饮食进一步均分为孕前肥胖-哺乳期高脂饮食组(n=6)、孕前肥胖-哺乳期标准饮食组(n=6)、孕期过度增重-哺乳期高脂饮食组(n=6)、孕期过度增重-哺乳期标准饮食组(n=6)。每组随机抽取12只子鼠(雌雄各半),共48只子鼠纳入研究;出生后第21天离乳,离乳后均饲喂标准饲料。哺乳期第0、7、14、21、28、35和42天测量子鼠体重;第28、35和42天(离乳后第7、14和21天)检测血中白细胞介素-6(IL-6)、铁调素(hepcidin)、铁蛋白(ferritin)、血红蛋白(Hgb)、平均血红蛋白量(Mch)和平均红细胞体积(Mcv)。结果与哺乳期高脂饮食组相比,标准饮食可显著降低孕前肥胖和孕期过度增重母鼠子代的体重;显著降低孕前肥胖母鼠子代的IL-6(第28天,152.97 pg/mL vs.105.24 pg/mL;第35天,155.15 pg/mL vs.110.53 pg/mL;第42天,155.4 pg/mL vs.139.02 pg/mL,P均<0.017)和Hepcidin的水平(119.99 ng/mL vs.99.67 ng/mL,P<0.05),升高Mch(22.43 pg vs.23.32 pg,P<0.05)和Mcv的水平(72.71 fL vs.75.71 fL,P<0.05);显著降低孕期过度增重母鼠子代的IL-6水平(第35天,140.21 pg/mL vs.127.57 pg/mL,P<0.017),升高Hgb(出生后第35天,107.25 g/L vs.112.92 g/L,P<0.017)和Mcv的水平(72.90 fL vs.74.34 fL,P<0.05)。此外,哺乳期标准饮食还显著降低了孕前肥胖母鼠子代的Ferritin(50.60 ng/mL vs.42.06 ng/mL,P<0.05)和Hgb(110.53 g/L vs.106.28 g/L,P<0.05)。调整炎性指标IL-6和Hepcidin后,哺乳期饮食对孕前肥胖和孕期过度增重母鼠子代多个铁相关指标的影响不再具有统计学意义。结论孕前肥胖和孕期过度增重母鼠哺乳期标准饮食可降低子鼠炎症反应、升高铁相关指标水平,且炎症反应可能在母鼠哺乳期饮食与子鼠铁相关指标的关联中发挥机制作用。

高盐饮食通过激活盐皮质受体引发Dahl SS大鼠肾损伤和高血压的新机制

盐敏感高血压作为一种顽固性高血压,其发病机制十分复杂。虽然盐皮质激素受体激活和肾损伤在盐敏感高血压的发展中起关键作用,但具体的病理机制目前并不明确。通过高盐饮食诱导建立达尔盐敏感(Dahl SS)大鼠高血压模型,探究盐敏感高血压及肾损伤产生的病理机制。与盐不敏感的SS-13BN大鼠相比,长期高盐饮食会造成Dahl SS大鼠肾脏中交感神经和肾素-血管紧张素-醛固酮系统(RAAS)的局部激活,最终激活盐皮质激素受体(MR),导致上皮钠通道(ENaC)表达增加、氧化应激与炎症反应增强,从而发生肾纤维化病变,并引发肾脏中磷酸化肌动蛋白(P-Cofilin)与足蛋白(Podocin)表达增加,造成足细胞损伤,最终引发肾损伤与高血压症状。

Impact of age on host responses to diet-induced obesity:Development of joint damage and metabolic set points

Background:Osteoarthritis is one of the leading causes of pain and disability worldwide,and a large percentage of patients with osteoarthritis are individuals who are also obese.In recent years,a series of animal models have demonstrated that obesity-inducing diets can result in synovial joint damage(both with and without the superimposition of trauma),which may be related to changes in percentage of body fat and a series of low-level systemic inflammatory mediators.Of note,there is a disparity between whether the dietary challenges commence at weaning,representing a weanling onset,or at skeletal maturity,representing an adult onset of obesity.We wished to evaluate the effect ofthe dietary exposure time and the age at which animals are exposed to a high-fat and high-sucrose(HFS) diet to determine whether these factors may result in disparate outcomes,as there is evidence suggesting that these factors result in differential metabolic disturbances.Based on dietary exposure time,we hypothesized that rats fed an HFS diet for 14 weeks from weaning(HFS Weanling) would demonstrate an increase in knee joint damage scores,whereas rats exposed to the HFS diet for 4 weeks,starting at 12 weeks of age(HFS Adult) and rats exposed to a standard chow diet(Chow)would not display an increase in knee joint damage scores.Methods:Male Sprague-Dawley rats were fed either an HFS diet for 14 weeks from weaning(HFS Weanling) or an HFS diet for 4 weeks,starting at 12 weeks of age(HFS Adult).At sacrifice,joints were scored using the modified Mankin Criteria,and serum was analyzed for a defined subset of inflammatory markers(Interleukin-6,leptin,monocyte chemoattractant protein-1,and tumor necrosis factorα).Results:When the HFS Weanling and HFS Adult groups were compared,both groups had a similar percent of body fat,although the HFS Weanling group had a significantly greater body mass than the HFS Adult group.The HFS Weanling and HFS Adult animals had a significant increase in body mass and percentage of body fat when compared to the Chow group.Although knee joint damage scores were low in all 3 groups,we found,contrary to our hypothesis,that the HFS Adult group had statistically significant greater knee joint damage scores than the Chow and HFS Weanling groups.Furthermore,we observed that the HFS Weanling group did not have significant differences in knee joint damage scores relative to the Chow group.Conclusion:These findings indicate that the HFS Weanling animals were better able to cope with the dietary challenge of an HFS diet than the HFS Adult group.Interestingly,when assessing various serum proinflammatory markers,no significant differences were detected between the HTS Adult and HFS Weanling groups.Although details regarding the mechanisms underlying an increase in knee joint damage scores in the HFS Adult group remain to be elucidated,these findings indicate that dietary exposure time maybe less important than the age at which an HFS diet is introduced.Moreover,increases in serum proinflammatory mediators do not appear to be directly linked to knee joint damage scores in the HFS Weanling group animals but may be partially responsible for the observed knee joint damage in the adults over the very short time of exposure to the HFS diet.

Changes of Neuronal Activities after Gut Electrical Stimulation with Different Parameters and Locations in Lateral Hypothalamus Area of Obese Rats

This study tested the effects of the gastrointestinal pulse train electrical stimulation with different parameters and at different locations on the neuronal activities of the lateral hypothalamus area（LHA） in obese rats in order to find the optimal stimulation parameter and location. Eight gastric electrical stimulations（GES） with different parameters were performed and the neuronal activities of gastric-distension responsive（GD-R） neurons in LHA were observed. The effects of stimulations with 8 parameters were compared to find the optimal parameter. Then the optimal parameter was used to perform electrical stimulation at duodenum and ileum, and the effects of the duodenal and ileac stimulation on the GD-R neurons in LHA were compared with the gastric stimulation of optimal parameter. The results showed that GES with the lowest energy parameter（0.3 ms, 3 mA, 20 Hz, 2 s on, 3 s off） activated the least neurons. The effects of GES with other parameters whose pulse width was 0.3 ms were not significantly different from those of the lowest energy parameter. Most gastric stimulations whose pulse width was 3 ms activated more LHA neurons than the smallest energy parameter stimulation, and the effects of those 3 ms gastric stimulations were similar. Accordingly, the lowest energy parameter was recognized as the optimal parameter. The effects of stimulations with the optimal parameter at stomach, duodenum and ileum on the LHA neuronal activities were not different. Collectively, gastrointestinal electrical stimulation（GIES） with relatively large pulse width might have stronger effects to the neuronal activities of GD-R neurons in LHA of obese rats. The effects of the GIES at different locations（stomach, duodenum and ileum） on those neurons are similar, and GES is preferential because of its easy clinical performance and safety.

小檗碱通过调节肠道菌群改善高脂饮食诱导的非酒精性脂肪性肝病大鼠肝组织炎症实验研究

目的探讨应用小檗碱(BBR)处理对高脂饮食诱导的非酒精性脂肪性肝病(NAFLD)大鼠肝组织炎症和肠道菌群的影响.方法将45只SD大鼠随机分为对照组、模型组和小檗碱处理组,每组15只.在模型组和小檗碱处理组,采用高脂饮食喂养诱导NAFLD模型.实验结束时取肝组织行病理学检查,取血清检测空腹血糖(FPG)和空腹胰岛素(FINS),计算胰岛素抵抗指数(IRI);采集粪便,采用16SrRNA序列分析法检测肠道菌群变化;采用ELISA法检测血清白细胞介素-6(IL-6)、IL-10和肿瘤坏死因子-α(TNF-α)水平.结果在高脂喂养16 w末,取2只动物肝组织检查,提示造模成功.在实验结束时,小檗碱处理组动物肝组织学病变明显改善;小檗碱处理组大鼠血清ALT、AST和LDL水平分别为(78.0±6.0)IU/L、(119.6±8.8)IU/L和(61.3±5.0)mg/dL,显著低于模型组[分别为(211.5±9.0)IU/L、(312.6±9.7)IU/L和(97.6±8.9)mg/dL,P<0.05],而血清HDL水平为(70.0±5.4)mg/dL,显著高于模型组[(14.6±5.7)mg/dL,P<0.05];小檗碱处理组FPG、FINS和IRI分别为(4.1±0.5)mmol/L、(12.7±0.9)mU/L和(2.8±0.4),显著低于模型组[分别为(5.9±0.9)mmol/L、(19.3±1.1)mU/L和(4.6±1.0),P<0.05];小檗碱处理组大鼠肠道毛螺旋菌属和梭菌属水平分别为(5.6±0.5)和(2.0±0.4),显著低于模型组[分别为(13.4±1.3)和(7.2±0.6),P<0.05],而瘤胃球菌和乳酸菌属水平分别为(2.4±0.5)和(2.9±0.5),显著高于模型组[分别为(1.0±0.2)和(1.1±0.2),P<0.05];小檗碱处理组大鼠血清IL-6和TNF-α水平分别为(52.1±9.8)pg/mL和(70.0±17.3)pg/mL,显著低于模型组[分别为(80.3±21.6)pg/mL和(120.8±22.6)pg/mL,P<0.05],而血清IL-10水平为(6.1±2.7)pg/mL,显著高于模型组[(3.4±1.8)pg/mL,P<0.05].结论小檗碱可以通过调节肠道菌群改善NAFLD大鼠肝组织炎症反应,有效抑制细胞因子活动水平.