Aim To evaluate liposome as an injectable delivery system of proteins, insulin was chosen as model drug and the hypoglycemic effect of PEG-coated liposomal insulin was tested.Methods The PEG-coated liposomal insulin w...Aim To evaluate liposome as an injectable delivery system of proteins, insulin was chosen as model drug and the hypoglycemic effect of PEG-coated liposomal insulin was tested.Methods The PEG-coated liposomal insulin was prepared by reversal-phase emulsion evaporation.For pharmacodynamic study, insulin (2.5 IU*kg-1) was intravenously administered in phosphated-buffered saline (PBS) solution, conventional liposomes, and PEG-coated liposomes, separately, to normal Wistar rats.Blood glucose levels were determined by the glucose oxidase method.Results The mean diameter of the PEG-coated liposomal insulin was 58.4 nm, while the encapsulation ratio reached 18.33%.After intravenous administration of insulin solution, insulin liposome, and PEG-coated liposomal insulin, the minimum blood glucose concentrations (Cmin %) reached 25.26±5.75%, 33.92±12.42%, and 42.39±10.5% of the initial level, respectively, and the time periods to reach the minimum blood glucose level (Tmin) were 0.7±0.3 h, 1.2±0.4 h, and 2.3±0.7 h, respectively.The relative pharmacological bioavailabilities of insulin liposome and PEG-coated liposomal insulin were 98.03% and 99.70%, respectively, compared with the control of insulin solution.Conclusion PEG-coated liposome can be developed as a relatively sustained injectable delivery system for insulin.Moreover, the liposome coated with PEG may have advantages over normal liposome.展开更多
Aim To reveal the main active components and the action mechanisms of Radix astragali on insulin sensitivity improvement, we have investigated the effects of polysaccharide portion and saponin portion of Radix astraga...Aim To reveal the main active components and the action mechanisms of Radix astragali on insulin sensitivity improvement, we have investigated the effects of polysaccharide portion and saponin portion of Radix astragali extracts on blood biochemical indices and related gene expression of dexamethasone-induced SD rats. Methods SD rats （6 per group） received 2 μg/day subcutaneous dexamethasone for 4 weeks plus same dose （10 g material/kg） of polysaccharide or saponin extracts of Radix astragali. Blood samples, kidney tissues and epididymal fat pads were taken at the end of the experiment. Serum triglyceride （TG）, total cholesterol （TC）, low density lipoprotein cholesterol （LDLC）, high density lipoprotein cholesterol （HDLC）, glucose （GLU） and insulin （INS） levels were measured, respectively, mRNA levels of angiotensinogen in kidney, adiponectin and leptin as well as TNF-α in epididymal fats were determined by RT-PCR assay using GAPDH gene as an internal control. Results Both of polysaccharide and saponin extracts of Radix astragali exhibited positive effects in reducing serum triglycerides, glucose, and insulin levels of dexamethasone-induced SD rats. The saponin group showed more improvements on quantitive insulin sensitivity check index （QUICKI） than the polysaccharide group did. Both of the extracts down-regulated kidney angiotensinogen and fat TNF-α mRNA levels while they were simultaneously up-regulating fat adiponectin and leptin mRNA levels. No significant difference was found between actions of the two extracts. Conclusion Both of polysaccharide and saponin extracts of Radix astragali can improve insulin sensitivity. This action might be closely related to down-regulation of angiotensinogen, TNF-α and up-regulation of adiponectin and leptin expression. The results partly explained the improvement of type Ⅱ diabetes and diabetic nephropathy by Radix astragali. The similar actions of the two crude extracts suggest that unknown key active compounds might exist in both and remain to be discovered.展开更多
AIM： To create a rabbit model of pediatric nonalcoholic steatohepatitis （NASH） and to evaluate the role of adiponectin in the process. METHODS： Thirty-two specific pathogen-free male New Zealand rabbits were divid...AIM： To create a rabbit model of pediatric nonalcoholic steatohepatitis （NASH） and to evaluate the role of adiponectin in the process. METHODS： Thirty-two specific pathogen-free male New Zealand rabbits were divided randomly into three groups： （1） the normal control group （n = 10） was fed with standard diet for 12 wk; （2） the model group A （n = 11）; and （3） model group B （n = 11） were fed with a highfat diet （standard diet ＋ 10% lard ＋ 2% cholesterol） for 8 and 12 wk, respectively. Hepatic histological changes were observed and biochemical parameters as well as serum levels of adiponectin, interleukin （IL）-6, IL-10 and tumor necrosis factor （TNF）-α were measured. RESULTS： Typical histological hepatic lesions of NASH were observed in both model groups described as liver steatosis, liver inflammatory infiltration, cytologic ballooning, perisinusoidal fibrosis and overall fibrosis. Compared with the normal control group, there were significant increases in model groups A and B in weight gain （1097.2 ± 72.3, 1360.5± 107.6 vs 928.0 ±58.1, P 〈 0.05, P 〈 0.01）, liver weight （93.81±6.64, 104.6±4.42 vs 54.4±1.71, P 〈 0.01）, Lg （ALT） （1.9±0.29, 1.84± 0.28 vs 1.60±0.17, P 〈 0.01）, and Lg （TG） （1.03 ±0.24, 1.16 ±0.33 vs 0.00 ±0.16, P 〈 0.01）. Weight gain was much more in model group B than in model group A （1360.5± 107.6 vs 1097.2 ±72.3, P 〈 0.05）. But, there was no significant difference between the two groups concerning the other indexes. Pro-inflammatory cytokines （IL-6 and TNF-α） increased in model group B compared with that of control and model group A （IL-6：1.86±0.21 vs 1.41 ±0.33, 1.38± 0.42, P 〈 0.01; TNF-α： 1.18±0.07 vs 0.66 ±0.08, 0.86 ±0.43, P 〈 0.01, P 〈 0.05）, whereas serum adiponectin and IL-10 decreased in model groups compared with that in the control （adiponectin： A： 21.87±4.84 and B： 21.48 ±4.60 vs 27.36 ±7.29, P 〈 0.05. IL-10： A： 1.72± 0.38 and B： 1.83 ±0.39 vs 2.26±0.24, P 〈 0.01）. Lg （TC） and the degree of liver fatty infiltration was an independent determinant of serum adiponectin level analyzed by stepwise multiple regressions, resulting in 29.4% of variances. CONCLUSION： This rabbit model produces the key features of pediatric NASH and may provide a realistic model for future studies. Adiponectin level partially reflects the severity of liver steatosis, but not the degree of liver inflammation.展开更多
AIM:To determine the associations between leptin and ghrelin concentrations and sustained virological response(SVR)in chronic hepatitis C patients with ste-atosis.METHODS:We retrospectively assessed 56 patients infect...AIM:To determine the associations between leptin and ghrelin concentrations and sustained virological response(SVR)in chronic hepatitis C patients with ste-atosis.METHODS:We retrospectively assessed 56 patients infected with hepatitis C virus(HCV)genotype-1 and 40 with HCV genotype-3.Patients with decompensated cirrhosis,and those with other causes of chronic liver disease,were excluded.Serum HCV-RNA concentra-tions were measured before the initiation of treatment;at weeks 12(for genotype 1 patients),24 and 48 during treatment;and 24 wk after the end of treatment.Genotype was determined using INNO-LIPA HCV as-says,and serum leptin and ghrelin concentrations were measured using enzyme-linked immunosorbent assay.Biopsy specimens were scored according to the Ishak system and steatosis was graded as mild,moderate,or severe,according to the Brunt classif ication.RESULTS:Overall,SVR was positively related to the presence of genotype-3,to biopsy-determined lower histological stage of liver disease,and lower grade of steatosis.Patients ≥ 40 years old tended to be less responsive to therapy.In genotype-1 infected pa-tients,SVR was associated with a lower grade of liver steatosis,milder fibrosis,and an absence of insulin resistance.Genotype-1 infected patients who did not achieve SVR had significantly higher leptin concen-trations at baseline,with significant increases as the severity of steatosis worsened,whereas those who achieved SVR had higher ghrelin concentrations.In genotype-3 infected patients,SVR was associated only with fibrosis stage and lower homeostasis model as-sessment insulin resistance at baseline,but not with the degree of steatosis or leptin concentrations.Geno-type-3 infected patients who achieved SVR showed signif icant decreases in ghrelin concentration at end of treatment.Baseline ghrelin concentrations were elevat-ed in responders of both genotypes who had moderate and severe steatosis.CONCLUSION:Increased serum leptin before treat-ment may predict non-SVR,especially in HCV geno-type-1 infected patients,whereas increased ghrelin may predict SVR in genotype-1.展开更多
bjectives. To investigate the role of endogenous heme oxygenase (HO)/carbon monoxide (CO) system in regulating the process of intussusception (IN) induced by administration of lipopolysaccharide (LPS) in rats. Methods...bjectives. To investigate the role of endogenous heme oxygenase (HO)/carbon monoxide (CO) system in regulating the process of intussusception (IN) induced by administration of lipopolysaccharide (LPS) in rats. Methods. IN model of rats were induced by lipopolysaccharide. HO activity was determined by the amount of bilirubin formation which was measured with a doublebeam spectrophotometer, and HbCO formation was measured by COoximeter. Results. The results showed that LPS (10mg/kg) caused IN in up to 40% of the rats at 6h after treatment of LPS. The incidence of IN were significantly increased by 50% (P<005) and by 832%(P<001) in HO substrate(hemeLlysinate)treated rats and in exogenous COtreated rats, respectively; but it was significantly decreased by 418%(P<005) after administration of ZnDPBG, an inhibitor of heme oxygenase (HO) activity. Furthermore, LPS increased HO activity, HbCO formation cGMP content within colic smooth muscle and the plasma level of cGMP, and these parameters were significantly elevated by 626%(P<001), 400%(P<001), 493%(P<005) and 38%(P<005), respectively, compared with LPSnonIN rats. Conclusion. It is suggested that endogenous HO/CO system plays an important role in the process of IN induced by LPS, and inhibition of HO activity may decrease the formation of IN.展开更多
The clinical implications of non-alcoholic fatty liver diseases(NAFLD)derive from their potential to progress to fibrosis and cirrhosis.Inappropriate dietary fat intake,excessive intake of soft drinks,insulin resistan...The clinical implications of non-alcoholic fatty liver diseases(NAFLD)derive from their potential to progress to fibrosis and cirrhosis.Inappropriate dietary fat intake,excessive intake of soft drinks,insulin resistance and increased oxidative stress results in increased free fatty acid delivery to the liver and increased hepatic triglyceride(TG)accumulation.An olive oil-rich diet decreases accumulation of TGs in the liver,improves postprandial TGs,glucose and glucagonlike peptide-1 responses in insulin-resistant subjects, and upregulates glucose transporter-2 expression in the liver.The principal mechanisms include:decreased nuclear factor-kappaB activation,decreased lowdensity lipoprotein oxidation,and improved insulin resistance by reduced production of inflammatory cytokines(tumor necrosis factor,interleukin-6)and improvement of jun N-terminal kinase-mediated phosphorylation of insulin receptor substrate-1.The beneficial effect of the Mediterranean diet is derived from monounsaturated fatty acids,mainly from olive oil.In this review,we describe the dietary sources of the monounsaturated fatty acids,the composition of olive oil,dietary fats and their relationship to insulin resistance and postprandial lipid and glucose responses in non-alcoholic steatohepatitis,clinical and experimental studies that assess the relationship between olive oil and NAFLD,and the mechanism by which olive oil ameliorates fatty liver,and we discuss future perspectives.展开更多
In this research, Lysolecithin-a substance made with 100% natural ingredients - was given to ICR mice as medication to measure its periodic effect on the noradrenalin (NA), dopamine (DA), and serotonin (5-HT) levels o...In this research, Lysolecithin-a substance made with 100% natural ingredients - was given to ICR mice as medication to measure its periodic effect on the noradrenalin (NA), dopamine (DA), and serotonin (5-HT) levels of the brain. Both ICR and SAM mice were separated into two groups - control group and Lysolecithin (K. Lysolecithin: hydrolytic lysolecithin) medicated group, and given 1-week preparation period. The K. Lysolecithin group was given 500mg/kg of K. Lysolecithin at 0.2mL per dosage for 4 weeks, and the control group was given the same amount of dosage of water during the same period. NA, DA and 5-HT concentrations were measured from the blood before medication and 8 weeks / 12 weeks / 16 weeks after the first medication. For the SAM mice, 8 weeks after they were medicated with K .Lysolecithin, Morris Water Maze Test was conducted for 7 consecutive days and then the concentrations were measured by drawing blood from the heart. The K. Lysolecithin medicated group showed a tendency to have a statistically significant higher concentrations of 5-HT and NA in the blood. Also, periodic examination showed that the monoamine levels were highest in the 12th week and declined thereafter.展开更多
AIM： To evaluate the effect of Chinese traditional medicinal prescription, JIANPI HUOXUE decoction （JHD） on cytokine secretion pathway in rat liver induced by lipopolysaccharide （LPS）. METHODS： Twenty-four male ...AIM： To evaluate the effect of Chinese traditional medicinal prescription, JIANPI HUOXUE decoction （JHD） on cytokine secretion pathway in rat liver induced by lipopolysaccharide （LPS）. METHODS： Twenty-four male SD rats were divided into normal group （n = 4）, model group （n = 10） and JHD group （n = 10） randomly. Rats in model group and JHD group were administrated with normal saline or JHD via gastrogavage respectively twice a day for 3 d. One hour after the last administration, rats were injected with LPS via tail vein, 50 μg/kg. Simultaneously, rats in normal group were injected with equivalent normal saline. After LPS stimulation for 1.5 h, serum and liver tissue were collected. Pathological change of liver tissues was observed through hematoxylineosin （H.E.） staining. Tumor necrosis factor alpha （TNF-α） in serum were assayed by enzyme linked immunosorbent assay （ELISA）. The protein expression of TNF-α, phosphorylated inhibit-κB （p-κB） and CD68 in liver were assayed by Western blot. The distribution of CD68 protein in liver was observed through immunohistochemical staining. The mRNA expression of TNF-α, interleukin-6 （IL-6）, CD14, toll-like receptor 2 （TLR2） and TLR4 in liver were assayed by real-time RT-PCR.RESULTS： Predominant microvesicular change, hepatocyte tumefaction and cytoplasm dilution were observed in liver tissues after LPS administration as well as obvious CD68 positive staining in hepatic sinusoidal. After LPS stimulation, serum TNF-α （31.35 ± 6.06 vs 12225.40 ± 9007.03, P 〈 0.05）, protein expression of CD68 （1.13 ± 0.49 vs 3.36 ±1.69, P 〈 0.05）, p-IκB （0.01 ±0.01 vs 2.07 ＋ 0.83, P 〈 0.01） and TNF-α （0.27 ± 0.13 vs 1.29 ± 0.37, P 〈 0.01） in liver and mRNA expression of TNF-α （1.96 ± 2.23 vs 21.45 ±6.00, P 〈 0.01）, IL-6 （4.80 ± 6.42 vs 193.50 ± 36.36, P 〈 0.01） and TLR2 （1.44 ± 0.62 vs 4.16 ± 0.08, P 〈 0.01） in liver were also increased significantly. These pathological changes were all improved in .1HD group. On the other hand, TLR4 mRNA （1.22 ± 0.30 vs 0.50 ± 0.15, P 〈 0.05） was down-regulated and CD14 mRNA increased but not significantly after LPS stimulation. CONCLUSION： JHD can inhibit cytokine secretion pathway induced by LPS in rat liver, which is probably associated with its regulation on CD68, p-IκB and endotoxin receptor TLR2.展开更多
文摘Aim To evaluate liposome as an injectable delivery system of proteins, insulin was chosen as model drug and the hypoglycemic effect of PEG-coated liposomal insulin was tested.Methods The PEG-coated liposomal insulin was prepared by reversal-phase emulsion evaporation.For pharmacodynamic study, insulin (2.5 IU*kg-1) was intravenously administered in phosphated-buffered saline (PBS) solution, conventional liposomes, and PEG-coated liposomes, separately, to normal Wistar rats.Blood glucose levels were determined by the glucose oxidase method.Results The mean diameter of the PEG-coated liposomal insulin was 58.4 nm, while the encapsulation ratio reached 18.33%.After intravenous administration of insulin solution, insulin liposome, and PEG-coated liposomal insulin, the minimum blood glucose concentrations (Cmin %) reached 25.26±5.75%, 33.92±12.42%, and 42.39±10.5% of the initial level, respectively, and the time periods to reach the minimum blood glucose level (Tmin) were 0.7±0.3 h, 1.2±0.4 h, and 2.3±0.7 h, respectively.The relative pharmacological bioavailabilities of insulin liposome and PEG-coated liposomal insulin were 98.03% and 99.70%, respectively, compared with the control of insulin solution.Conclusion PEG-coated liposome can be developed as a relatively sustained injectable delivery system for insulin.Moreover, the liposome coated with PEG may have advantages over normal liposome.
文摘Aim To reveal the main active components and the action mechanisms of Radix astragali on insulin sensitivity improvement, we have investigated the effects of polysaccharide portion and saponin portion of Radix astragali extracts on blood biochemical indices and related gene expression of dexamethasone-induced SD rats. Methods SD rats （6 per group） received 2 μg/day subcutaneous dexamethasone for 4 weeks plus same dose （10 g material/kg） of polysaccharide or saponin extracts of Radix astragali. Blood samples, kidney tissues and epididymal fat pads were taken at the end of the experiment. Serum triglyceride （TG）, total cholesterol （TC）, low density lipoprotein cholesterol （LDLC）, high density lipoprotein cholesterol （HDLC）, glucose （GLU） and insulin （INS） levels were measured, respectively, mRNA levels of angiotensinogen in kidney, adiponectin and leptin as well as TNF-α in epididymal fats were determined by RT-PCR assay using GAPDH gene as an internal control. Results Both of polysaccharide and saponin extracts of Radix astragali exhibited positive effects in reducing serum triglycerides, glucose, and insulin levels of dexamethasone-induced SD rats. The saponin group showed more improvements on quantitive insulin sensitivity check index （QUICKI） than the polysaccharide group did. Both of the extracts down-regulated kidney angiotensinogen and fat TNF-α mRNA levels while they were simultaneously up-regulating fat adiponectin and leptin mRNA levels. No significant difference was found between actions of the two extracts. Conclusion Both of polysaccharide and saponin extracts of Radix astragali can improve insulin sensitivity. This action might be closely related to down-regulation of angiotensinogen, TNF-α and up-regulation of adiponectin and leptin expression. The results partly explained the improvement of type Ⅱ diabetes and diabetic nephropathy by Radix astragali. The similar actions of the two crude extracts suggest that unknown key active compounds might exist in both and remain to be discovered.
基金Supported by The funds for programs of Zhejiang Provincial Natural Science, No.Y2080047Major Programs of Zhejiang Provincial Medical and Health Science and Technology & Chinese Ministry of Health, No.WKJ2008-2-026Special Major Programs of Zhejiang Provincial Science and Technology, No. 2008c03002-1
文摘AIM： To create a rabbit model of pediatric nonalcoholic steatohepatitis （NASH） and to evaluate the role of adiponectin in the process. METHODS： Thirty-two specific pathogen-free male New Zealand rabbits were divided randomly into three groups： （1） the normal control group （n = 10） was fed with standard diet for 12 wk; （2） the model group A （n = 11）; and （3） model group B （n = 11） were fed with a highfat diet （standard diet ＋ 10% lard ＋ 2% cholesterol） for 8 and 12 wk, respectively. Hepatic histological changes were observed and biochemical parameters as well as serum levels of adiponectin, interleukin （IL）-6, IL-10 and tumor necrosis factor （TNF）-α were measured. RESULTS： Typical histological hepatic lesions of NASH were observed in both model groups described as liver steatosis, liver inflammatory infiltration, cytologic ballooning, perisinusoidal fibrosis and overall fibrosis. Compared with the normal control group, there were significant increases in model groups A and B in weight gain （1097.2 ± 72.3, 1360.5± 107.6 vs 928.0 ±58.1, P 〈 0.05, P 〈 0.01）, liver weight （93.81±6.64, 104.6±4.42 vs 54.4±1.71, P 〈 0.01）, Lg （ALT） （1.9±0.29, 1.84± 0.28 vs 1.60±0.17, P 〈 0.01）, and Lg （TG） （1.03 ±0.24, 1.16 ±0.33 vs 0.00 ±0.16, P 〈 0.01）. Weight gain was much more in model group B than in model group A （1360.5± 107.6 vs 1097.2 ±72.3, P 〈 0.05）. But, there was no significant difference between the two groups concerning the other indexes. Pro-inflammatory cytokines （IL-6 and TNF-α） increased in model group B compared with that of control and model group A （IL-6：1.86±0.21 vs 1.41 ±0.33, 1.38± 0.42, P 〈 0.01; TNF-α： 1.18±0.07 vs 0.66 ±0.08, 0.86 ±0.43, P 〈 0.01, P 〈 0.05）, whereas serum adiponectin and IL-10 decreased in model groups compared with that in the control （adiponectin： A： 21.87±4.84 and B： 21.48 ±4.60 vs 27.36 ±7.29, P 〈 0.05. IL-10： A： 1.72± 0.38 and B： 1.83 ±0.39 vs 2.26±0.24, P 〈 0.01）. Lg （TC） and the degree of liver fatty infiltration was an independent determinant of serum adiponectin level analyzed by stepwise multiple regressions, resulting in 29.4% of variances. CONCLUSION： This rabbit model produces the key features of pediatric NASH and may provide a realistic model for future studies. Adiponectin level partially reflects the severity of liver steatosis, but not the degree of liver inflammation.
文摘AIM:To determine the associations between leptin and ghrelin concentrations and sustained virological response(SVR)in chronic hepatitis C patients with ste-atosis.METHODS:We retrospectively assessed 56 patients infected with hepatitis C virus(HCV)genotype-1 and 40 with HCV genotype-3.Patients with decompensated cirrhosis,and those with other causes of chronic liver disease,were excluded.Serum HCV-RNA concentra-tions were measured before the initiation of treatment;at weeks 12(for genotype 1 patients),24 and 48 during treatment;and 24 wk after the end of treatment.Genotype was determined using INNO-LIPA HCV as-says,and serum leptin and ghrelin concentrations were measured using enzyme-linked immunosorbent assay.Biopsy specimens were scored according to the Ishak system and steatosis was graded as mild,moderate,or severe,according to the Brunt classif ication.RESULTS:Overall,SVR was positively related to the presence of genotype-3,to biopsy-determined lower histological stage of liver disease,and lower grade of steatosis.Patients ≥ 40 years old tended to be less responsive to therapy.In genotype-1 infected pa-tients,SVR was associated with a lower grade of liver steatosis,milder fibrosis,and an absence of insulin resistance.Genotype-1 infected patients who did not achieve SVR had significantly higher leptin concen-trations at baseline,with significant increases as the severity of steatosis worsened,whereas those who achieved SVR had higher ghrelin concentrations.In genotype-3 infected patients,SVR was associated only with fibrosis stage and lower homeostasis model as-sessment insulin resistance at baseline,but not with the degree of steatosis or leptin concentrations.Geno-type-3 infected patients who achieved SVR showed signif icant decreases in ghrelin concentration at end of treatment.Baseline ghrelin concentrations were elevat-ed in responders of both genotypes who had moderate and severe steatosis.CONCLUSION:Increased serum leptin before treat-ment may predict non-SVR,especially in HCV geno-type-1 infected patients,whereas increased ghrelin may predict SVR in genotype-1.
文摘bjectives. To investigate the role of endogenous heme oxygenase (HO)/carbon monoxide (CO) system in regulating the process of intussusception (IN) induced by administration of lipopolysaccharide (LPS) in rats. Methods. IN model of rats were induced by lipopolysaccharide. HO activity was determined by the amount of bilirubin formation which was measured with a doublebeam spectrophotometer, and HbCO formation was measured by COoximeter. Results. The results showed that LPS (10mg/kg) caused IN in up to 40% of the rats at 6h after treatment of LPS. The incidence of IN were significantly increased by 50% (P<005) and by 832%(P<001) in HO substrate(hemeLlysinate)treated rats and in exogenous COtreated rats, respectively; but it was significantly decreased by 418%(P<005) after administration of ZnDPBG, an inhibitor of heme oxygenase (HO) activity. Furthermore, LPS increased HO activity, HbCO formation cGMP content within colic smooth muscle and the plasma level of cGMP, and these parameters were significantly elevated by 626%(P<001), 400%(P<001), 493%(P<005) and 38%(P<005), respectively, compared with LPSnonIN rats. Conclusion. It is suggested that endogenous HO/CO system plays an important role in the process of IN induced by LPS, and inhibition of HO activity may decrease the formation of IN.
文摘The clinical implications of non-alcoholic fatty liver diseases(NAFLD)derive from their potential to progress to fibrosis and cirrhosis.Inappropriate dietary fat intake,excessive intake of soft drinks,insulin resistance and increased oxidative stress results in increased free fatty acid delivery to the liver and increased hepatic triglyceride(TG)accumulation.An olive oil-rich diet decreases accumulation of TGs in the liver,improves postprandial TGs,glucose and glucagonlike peptide-1 responses in insulin-resistant subjects, and upregulates glucose transporter-2 expression in the liver.The principal mechanisms include:decreased nuclear factor-kappaB activation,decreased lowdensity lipoprotein oxidation,and improved insulin resistance by reduced production of inflammatory cytokines(tumor necrosis factor,interleukin-6)and improvement of jun N-terminal kinase-mediated phosphorylation of insulin receptor substrate-1.The beneficial effect of the Mediterranean diet is derived from monounsaturated fatty acids,mainly from olive oil.In this review,we describe the dietary sources of the monounsaturated fatty acids,the composition of olive oil,dietary fats and their relationship to insulin resistance and postprandial lipid and glucose responses in non-alcoholic steatohepatitis,clinical and experimental studies that assess the relationship between olive oil and NAFLD,and the mechanism by which olive oil ameliorates fatty liver,and we discuss future perspectives.
文摘In this research, Lysolecithin-a substance made with 100% natural ingredients - was given to ICR mice as medication to measure its periodic effect on the noradrenalin (NA), dopamine (DA), and serotonin (5-HT) levels of the brain. Both ICR and SAM mice were separated into two groups - control group and Lysolecithin (K. Lysolecithin: hydrolytic lysolecithin) medicated group, and given 1-week preparation period. The K. Lysolecithin group was given 500mg/kg of K. Lysolecithin at 0.2mL per dosage for 4 weeks, and the control group was given the same amount of dosage of water during the same period. NA, DA and 5-HT concentrations were measured from the blood before medication and 8 weeks / 12 weeks / 16 weeks after the first medication. For the SAM mice, 8 weeks after they were medicated with K .Lysolecithin, Morris Water Maze Test was conducted for 7 consecutive days and then the concentrations were measured by drawing blood from the heart. The K. Lysolecithin medicated group showed a tendency to have a statistically significant higher concentrations of 5-HT and NA in the blood. Also, periodic examination showed that the monoamine levels were highest in the 12th week and declined thereafter.
基金Supported by The National Natural Science Foundation of China, No.30371818Shanghai Rising-Star Program, No. 07QA14052Shanghai Leading Academic Discipline Project, Y0302 and Shanghai Educational Development Foundation, No. 2007CG56
文摘AIM： To evaluate the effect of Chinese traditional medicinal prescription, JIANPI HUOXUE decoction （JHD） on cytokine secretion pathway in rat liver induced by lipopolysaccharide （LPS）. METHODS： Twenty-four male SD rats were divided into normal group （n = 4）, model group （n = 10） and JHD group （n = 10） randomly. Rats in model group and JHD group were administrated with normal saline or JHD via gastrogavage respectively twice a day for 3 d. One hour after the last administration, rats were injected with LPS via tail vein, 50 μg/kg. Simultaneously, rats in normal group were injected with equivalent normal saline. After LPS stimulation for 1.5 h, serum and liver tissue were collected. Pathological change of liver tissues was observed through hematoxylineosin （H.E.） staining. Tumor necrosis factor alpha （TNF-α） in serum were assayed by enzyme linked immunosorbent assay （ELISA）. The protein expression of TNF-α, phosphorylated inhibit-κB （p-κB） and CD68 in liver were assayed by Western blot. The distribution of CD68 protein in liver was observed through immunohistochemical staining. The mRNA expression of TNF-α, interleukin-6 （IL-6）, CD14, toll-like receptor 2 （TLR2） and TLR4 in liver were assayed by real-time RT-PCR.RESULTS： Predominant microvesicular change, hepatocyte tumefaction and cytoplasm dilution were observed in liver tissues after LPS administration as well as obvious CD68 positive staining in hepatic sinusoidal. After LPS stimulation, serum TNF-α （31.35 ± 6.06 vs 12225.40 ± 9007.03, P 〈 0.05）, protein expression of CD68 （1.13 ± 0.49 vs 3.36 ±1.69, P 〈 0.05）, p-IκB （0.01 ±0.01 vs 2.07 ＋ 0.83, P 〈 0.01） and TNF-α （0.27 ± 0.13 vs 1.29 ± 0.37, P 〈 0.01） in liver and mRNA expression of TNF-α （1.96 ± 2.23 vs 21.45 ±6.00, P 〈 0.01）, IL-6 （4.80 ± 6.42 vs 193.50 ± 36.36, P 〈 0.01） and TLR2 （1.44 ± 0.62 vs 4.16 ± 0.08, P 〈 0.01） in liver were also increased significantly. These pathological changes were all improved in .1HD group. On the other hand, TLR4 mRNA （1.22 ± 0.30 vs 0.50 ± 0.15, P 〈 0.05） was down-regulated and CD14 mRNA increased but not significantly after LPS stimulation. CONCLUSION： JHD can inhibit cytokine secretion pathway induced by LPS in rat liver, which is probably associated with its regulation on CD68, p-IκB and endotoxin receptor TLR2.
