参照点关系的延续与变化——“大抵”的语法化研究

以名词性成分为源头,“大抵”分别演变为范围副词、程度副词和情态副词。范围副词用法主要用于限定表示事件和数量的结构,程度副词用法则用于说明行为或状态的程度,它们都表示“约量”义。由于参照点关系发生变化,凸显“约量”让位于凸显不确定性,“大抵”因而演变为表示可能认识情态的副词。

Research on the protection effect of pioglitazone for non-alcoholic fatty liver disease (NAFLD)in rats

Objective： The prevalence of non-alcoholic fatty liver disease （NAFLD） has markedly increased. Insulin resistance has been implicated in the pathogenesis of NAFLD. This study was aimed at observing the relationship between insulin resistance and NAFLD, and evaluating the role of pioglitazone （PGZ） acting as insulin-sensitizing agents in the prevention and treatment of rat fatty liver induced by high fat feeding. Methods： The rats were separated randomly into 6 groups： model group Ⅰ were fed high fat diet for 8 weeks, PGZ prevention group were given PGZ 4 mg/（kg.d） simultaneously, while control group Ⅰ were fed normal food for 8 weeks; model group Ⅱ were fed high fat diet for 16 weeks, PGZ treatment group were given PGZ 4 mg/（kg.d） orally simultaneous with high fat diet for 8 weeks after high fat feeding for 8 weeks, control group Ⅱ were fed normal food for 16 weeks. The rats were sacrificed after 8 weeks and 16 weeks respectively. Liver weight, body weight, serum activities of alanine aminotransferase （ALT）, aspartate aminotransferase （AST）, alkaline phosphatase （ALP）, tumor necrosis factor alpha （TNF-α）, fasting blood glucose （FBG）, fasting plasma insulin （FINS）, HOMA （homeostasis model assessment） insulin resistance index （HOMA-IR）, and the liver histology of rats of all groups were assayed. Results： After 8 weeks, the liver in model group Ⅰ showed typical steatosis, accompanied with mild to moderate lobular inflammatory cell infiltration, liver indexes and serum levels of ALT, AST, ALP, TNF-α were significantly increased （P〈0.05） compared with control group Ⅰ. Whereas, the degree of hepatic injury was attenuated in PGZ prevention group, liver indexes and serum levels of ALT, ALP were significantly decreased （P〈0.05） compared with model group Ⅰ. After 16 weeks, notable steatosis, and lobular inflammation were observed in model group Ⅱ rat liver, while the degree of hepatic injury was attenuated in the PGZ treatment group. Liver index, serum levels ofALT, AST, ALP, FINS and HOMA-IR were significantly increased （P〈0.05） in model group Ⅱ compared with control group Ⅱ. Whereas, in PGZ treatment group, serum levels of AST and FINS showed decreasing tendency, liver indexes, serum levels of ALT, ALP, TNF-α and HOMA-IR were significantly decreased compared with model group Ⅱ. Conclusion： Insulin resistance plays a role in the pathogenesis of NAFLD in rats. Pioglitazone can attenuate insulin resistance and biochemical and histological injury in high fat-induced fatty liver in rats.

Yi-Qi-Zeng-Min-Tang,a Chinese medicine,ameliorates insulin resistance in type 2 diabetic rats

AIM:To investigate the effects of the Chinese herbal decoction,Yi-Qi-Zeng-Min-Tang(YQZMT),on insulin resistance in type 2 diabetic rats.METHODS:Sprague-Dawley rats were divided into two dietary regiments by feeding either normal pellet diet(NPD) or high fat diet(HFD).Four weeks later,the HFD-fed rats were injected intraperitoneally with lowdose streptozotocin(STZ).Rats with non-fasting blood glucose level ≥ 16.67 mmol/L were considered type 2 diabetic and further divided into five subgroups:the type 2 diabetes model group,low-dose,medium-doseand high-dose YQZMT groups,and rosiglitazone group.Age-matched NPD-fed rats served as controls.YQZMT or rosiglitazone were administered for 8 wk.Intraperitoneal glucose and insulin tolerance tests were performed before and after the treatment to measure the glucose tolerance and insulin sensitivity.Serum levels of biochemical parameters,adipocytokines,such as tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),as well as free fatty acids(FFAs),were also analyzed.RESULTS:There was significant elevation of insulin resistance and serum levels of fasting glucose(12.82 ± 1.08 mmol/L vs 3.60 ± 0.31 mmol/L,P < 0.01),insulin(7197.36 ± 253.89 pg/mL vs 4820.49 ± 326.89 pg/mL,P < 0.01),total cholesterol(TC)(8.40 ± 0.49 mmol/L vs 2.14 ± 0.06 mmol/L,P < 0.01),triglyceride(2.24 ± 0.12 mmol/L vs 0.78 ± 0.05 mmol/L,P < 0.01),low-density lipoprotein cholesterol(LDL-c)(7.84 ± 0.51 mmol/L vs 0.72 ± 0.04 mmol/L,P < 0.01) and decrease in high-density lipoprotein cholesterol(HDL-c)(0.57 ± 0.03 mmol/L vs 1.27 ± 0.03 mmol/L,P < 0.01) in the low-dose STZ and high-fat diet induced type 2 diabetic group when compared with the control group.Administration of YQZMT induced dose-and timedependent changes in insulin resistance,glucose and lipid profile,and reduced levels of FFA,TNF-α and IL-6 in the type 2 diabetic rats.After the treatment,compared with the diabetic group,the insulin resistance was ameliorated in the high-dose YQZMT(2.82 g/100 g per day) group,with a significant reduction in serum glucose(12.16 ± 1.00 mmol/L vs 17.65 ± 2.22 mmol/L,P < 0.01),homeostasis model assessment of basal insulin resistance(22.68 ± 2.37 vs 38.79 ± 9.02,P < 0.05),triglyceride(0.87 ± 0.15 mmol/L vs 1.99 ± 0.26 mmol/L,P < 0.01),TC(3.31 ± 0.52 mmol/L vs 6.50 ± 1.04 mmol/L,P < 0.01) and LDL-c(2.47 ± 0.50 mmol/L vs 6.00 ± 1.07 mmol/L,P < 0.01),and a signif icant increase in HDL-c(0.84 ± 0.08 mmol/L vs 0.50 ± 0.03 mmol/L,P < 0.01).But the body weight was not changed signif icantly.CONCLUSION:YQZMT,which ameliorates insulin resistance and does not cause increase in body weight,may be a suitable therapeutic adjunct for the treatment of type 2 diabetes.

Modelling time series properties of Australian lending interest rates

The purpose of this paper is to examine the time series properties of Australian residential mortgage interest rates, and in doing so, establish whether or not selected home loan rates （product-level monthly home loan interest rates for CBA） exhibit the expected cyclical and seasonal variations and whether seasonality, if present, is stochastic or deterministic. In particular, due to a well established presence of cyclicality in financial markets＇ interest rates and strong correlation between financial markets＇ interest rates and home loan interest rates, the paper presumes that cyclicality is also to be found in home loan interest rates. Furthermore, the paper tests the hypothesis that home loan interest rates, for selected products, exhibit the three identified （＂Spring＂, ＂Autumn＂ and ＂The end of the Financial Year＂） season-related interest rate reductions. The paper uses a structural time series modelling approach and product-level home loan interest rates data from one of the biggest banks in Australia, Commonwealth Bank of Australia （CBA）. As expected, the results overall confirm the existence of cyclicality in home loan interest rates. With respect to the seasonality of home loan interest rate, although most of the analysed variables show the presence of statistically significant seasonal factors, the majority of the statistically significant seasonal factors observed cannot be attributed to any of the three considered seasonal effects.

Effects and mechanism of different adrenergic receptor antagonists on left ventricular hypertrophy subsequent to coarctation of abdominal aorta in rats

Objective: To study the changes of a collagen-binding protein (Colligin) and myosin heavy chain isoform (α/β-MHC) gene and protein in left ventricular hypertrophy subsequent to coarctation of abdominal aorta in rats and the effects of three kinds of adrenergic receptor blockers: Carvedilol (CAR) , Metoprolol (MET) and Terazosin (TER) on these changes, and to elucidate the effects and new mechanism of CAR on left ventricular hypertrophy regression. Methods: A model of hypertrophy induced by coarctation of abdominal aorta(CAA)was used in this study. Thirty two male wistar rats were divided randomly into four groups 4 weeks after CAA operation: CAA, CAR, MET and TER. Hemodynamics, ventricular remodeling parameters, expressions of Colligin and α/β-MHC mRNA, protein expressions of Collagen Ⅰ / Ⅲ and Colligin were investigated in the four groups and sham operation group. Results: Left ventricle hypertrophy was observed clearly 16 weeks after operation. The ratio of α/β-MHC mRNA decreased, while expressions of Collagen Ⅰ /Ⅲ proteins and Colligin mRNA/protein increased( P < 0.05). CAR could ameliorate left ventricle hypertrophy prior to MET and TER. CAR could also change the expressions of α/β-MHC, Collagen Ⅰ /Ⅲ and Colligin in both gene and protein levels ( P < 0.05), while MET and TER have no effect on them ( P > 0.05). Conclusion: The effects of CAR on extracellular matrix proteins and MHC isoform shift regression of left ventricle may be due to antiproliferative or antioxidative mechanism, which was independent of beta-adrenergic receptor antagonist.

Tangnaikang improves insulin resistance and β-cell apoptosis by ameliorating metabolic inflammation in SHR.Cg-Lepr^(cp)/NDmcr rats

OBJECTIVE: To investigate the effects of Tangnaikang(TNK), a mixture of five herbal plant extracts,on inflammation-mediated insulin resistance andβ-cell apoptosis in SHR.Cg-Leprcp/NDmcr(SHR-cp)rats.METHODS: Seven-week-old SHR-cp rats were randomly divided into a control(CON) group and a TNK(3.24 g/kg) group. Wistar-Kyoto rats at the same age were used as the normal control group.After 7 weeks of continuous intragastric administration of TNK, the glucose metabolic status and insulin sensitivity of the rats were evaluated by assessing fasting serum glucose(FBG), the oral glucose tolerance test(OGTT), fasting serum insulin(FINS),and the insulin sensitivity index(ISI). Serum tumor necrosis factor-α(TNF-α), interleukin-6(IL-6), C-reactive protein(CRP) and adiponectin were measured via enzyme-linked immunosorbent assays.Macrophage infiltration and apoptosis in adipose tissues were detected through F4/80 immunohistochemistry and the terminal deoxynucleotidyl transferase d UTP nick end labeling(TUNEL) assay. Islet morphology and β-cell apoptosis were investigated using double immunofluorescence staining and the TUNEL assay. The expression of cytokine genes in adipose tissue, the liver, and the pancreas was detected in real-time polymerase chain reaction assays. The expression and phosphorylation levels of insulin signaling-, inflammation-, and β-cell survival-related proteins in the liver and pancreas of SHR-cp rats were detected by western blotting.RESULTS: TNK(3.24 g/kg) treatment significantly decreased body weight, FBG and FINS; improved impaired glucose tolerance; increased the ISI; reduced serum levels of TNF-α, CRP and IL-6; and increased serum adiponectin. The m RNA expression of inflammatory markers was markedly reduced in the liver, pancreas, and adipose tissue. F4/80-and TUNEL-positive cells in adipose tissues were decreased, as was the number of TUNEL-positiveβ-cells. The phosphorylation of c-Jun N-terminal kinase and that of insulin receptor substrate-1 at serines 307 and 1101 was significantly decreased.In the pancreas, the expression of nuclear factor kappa-light chain-enhancer of activated B cells-p65 was significantly decreased, and phosphoinositide3-kinase and IRS-2 were significantly increased.CONCLUSION: TNK was able to improve insulin resistance and β-cell apoptosis in SHR-cp rats, which might be associated with its ability to relieve the overall and local metabolic inflammatory responses observed in SHR-cp rats.

Influence of catgut implantation at acupoints on leptin and insulin resistance in simple obesity rats

OBJECTIVES:To investigate the influence of catgut implantation at acupoints on leptin resistance(LR) and insulin resistance(IR) in the simple obesity rat.METHODS:Rats were made obese with high-fat diets,after which surgical catgut was implanted at Zusanli(ST 36) and Neiting(ST 44) acupoints once a week for 4 weeks(implantation group).Rats from the implantation group were compared with normal rats and unoperated obese rats(control group).Gene expression of the leptin receptor(OB-R) was evaluated using RT-PCR and northern blot.Serum and hypothalamus leptin and insulin(INS) levels were determined by radioimmunoassay.Body weight,Lee's index,body fat,serum and hypothalamus leptin and INS levels,and hypothalamic OB-R gene expression were determined before and after treatment.RESULTS:Body weights,Lee's index,body fat,and serum leptin and INS levels were significantly higher in obese than in normal rats.Hypothalamic leptin and INS levels and OB-R gene expression were significantly lower in obese rats.Catgut implantation at acupoint promoted weight loss and decreased serum leptin and INS levels.Hypothalamic leptin and INS levels and OB-R gene expression increased significantly.CONCLUSIONS:Catgut implantation at acupoint adjusts central and peripheral leptin and promotes hypothalamic OB-R gene expression.This may be an important method for regulation of LR,IR and abnormal endocrinology and metabolism.

Effect on the Akt2 in Skeletal Muscle of Rats with Insulin Resistance Treated by Acupuncture

Objective： To observe the effect of acupuncture on Akt2 mRNA expression in skeletal muscle of insulin resistant rat models. Methods： Twenty-four SD rats were randomly divided into a control group, a model group and an acupuncture group. Fasting plasma glucose （FPG）, fasting insulin （FINS）, insulin sensitivity index （ISI）, C peptide （C-P）, as well as Akt2 mRNA expression in skeletal muscle of rats were detected by glucose oxidase method, ELISA and real-time PCR. Results： Compared with the control group, the level of FP~ FINS and C-P increased significantly （P〈0.01） while ISI and Akt2 mRNA expression decreased markedly in the model group （P〈0.01, P〈0.05）. In the acupuncture group, the levels of FPC FINS and C-P were much lower than in the model group （P〈0.01, P〈0.01, P〈0.05） and ISI and Akt2 mRNA expression increased markedly （P〈0.01）. Conclusion： The mechanism of acupuncture in treating insulin resistance may relate to the up-regulated of the Akt2 mRNA expression and to the improvement of the signal transduction of PI3K pathway.

Effects of Danqidihuang Granules on glucolipid metabolism in insulin-resistant rats

OBJECTIVE： To explore whether the insulin resis- tance （IR） model could be established through feed- ing Sprague-Dawley （SD） rats high-sugar and high-fat diets and to further observe the preven- tive and treatment effects of different doses of Dan- qidihuang Granules in rats. METHODS： Thirty-two SD rats were divided ran- domly into control group A （given regular feed）, model group B （food high in sugar and fat）, inter- vention group C （food high in sugar and fat as well as regular doses of Danqidihuang Granules）, and in- tervention group D （food high in sugar and fat as well as double doses of Danqidihuang Granules）. The interventions were for 8 weeks. Motion, change in color, body weight, and food intake, as well as plasma lipids （including low-density lipopro- tein-cholesterol （LDL-C）, high-density lipopro- tein-cholesterol （HDL-C）, total cholesterol （TC） and triglyceride （TG）, fasting blood glucose （FBG）, fast-ing insulin （FINs） levels, insulin sensitivity index （ISI）, and insulin resistance index （HOMO-IR） were observed. RESULTS： At the end of the second week of the ex- periment, the appetite and activities of rats in groups B, C and D decreased significantly com- pared with group A. The fur of the rats in those three groups was curly. After the fourth week, the activities, food intake and color of rats in group B were worse than those in groups C and D, but there were no significant differences in weight （P〉0.05）. Compared with group A, LDL-C, TC, FBG and HO- MO-IR in model group 13 were increased significant- ly （P〈0.05）, whereas the FINs and ISI increased obvi- ously （P〈0.05）. The levels of LDL-C and TC in group D was decreased obviously compared with those in group C, and HOMO-IR in group D was less than that in group B CP〈0.05）. CONCLUSION： Danqidihuang Granules helped to prevent and improved the insulin resistance of rats.

Ileal transposition rapidly improves glucose tolerance and gradually improves insulin resistance in non-obese type 2 diabetic rats

Background:Many studies have confirmed that ileal transposition can improve type 2 diabetes mellitus(T2DM),accompanied by increased glucagon-like peptide-1(GLP-1).We performed the experiment on diabetic rats to evaluate the effects and mechanisms of ileal transposition on the glycemic metabolism.Methods:Twenty Goto-Kakizaki(GK)rats were randomly divided into the ileal transposition group(IT group)and the sham operation group(Shamgroup).Weight,food intake,fasting plasma glucose(FPG),fasting insulin(F-ins),oral glucose tolerance test(OGTT)and GLP-1 were determined at baseline and 1,4,8,16 and 24weeks post-operatively.The homeostasis model assessment-insulin resistance(HOMA-IR)index and the area under the curve(AUC)during OGTT were measured.Histological determination of the GLP-1 receptor(GLP-1R)was performed on the pancreas and ileum24weeks post-operatively.Results:In comparison with the Sham group,the IT group showed a higher GLP-1 level and lower AUC at 4,8,16 and 24 weeks post-operatively(all P<0.05)and a lower FPG,F-ins levels and HOMA-IR at 8,16 and 24 weeks post-operatively(all P<0.05).Compared with baseline levels,the plasma GLP-1,AUC and FPG levels decreased significantly at each postoperative time point in the IT group(all P<0.05),but not in the Sham group(all P>0.05);F-ins and HOMA-IR significantly decreased at 8,16 and 24 weeks post-operatively in the IT group(all P<0.05).GLP-1R expression in the IT group was significantly higher than that of the Sham group in both the pancreas and the ileum at 24 weeks post-operatively(P<0.05).Conclusions:Ileal transposition ameliorated glucose metabolism without reduction in weight or food intake in GK rats,which may be induced by the increased GLP-1 expression.However,the delayed improvement of insulin resistance,accompanied by decreased plasma insulin levels,might not directly result from the increased GLP-1.