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Objective To investigate the influence of gestational vitamin A(VA) deficiency on lipid synthesis in offspring liver tissue by using the rat model of gestational vitamin A deficiency.Methods The rat model of gestational VA deficiency was established and divided into the normal AV,VA deficiency and VA deficiency and supplement (VAD) groups.The offspring blood lipid levels were detected.The mRNA expression changes of lipid synthesis molecule ACC1,FAS and SREBP1 in liver were detected;the lipid droplet deposition situation after HE staining in offspring liver tissue section was observed.Results The HDL-C level of the VAD group was significantly lower than that of the VA normal group(VAN group and VAS group,P＜0.05),and the difference between the VAN group and VAS group had no statistical difference(P＞0.05).The TG level had statistically significant difference among the three groups(P＜0.05).The ACC1,FAS and SREBP1 mRNA expression levels in the VAD group were significantly increased.The liver in the VAD group appeared more lipid droplet deposit with partial lipid droplet vacuoles in cytoplasm;while the liver cells in the VAS and VAN groups showed the regular arrangement without obvious lipid droplet deposit.Conclusion Gestational VA deficiency may induce the abnormal activation of liver lipid synthesis pathway in rat offspring and causes lipid metabolic disturbance.
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Objective To study the changes and significance of 11β-HSD1 and 11β-HSD2 gene and protein expression in pla-centa of patients with gestational diabetes mellitus .Methods Thirty pregnant women with gestational diabetes mellitus (GDM ) and normal glucose tolerance (NGT ) were selected .Chemiluminescence was used to determine the serum cortisol ,neonatal cord blood cortisol and fasting insulin ect .Immunohistochemistry was used to detect the expression location of 11β-HSD1 and 11β-HSD2 in the placenta .The differential expression of 11β-HSD1 and 11β-HSD2 genes and proteins were detected by real-time PCR and Western blot .Results Compared with NGT group ,fasting insulin ,HOMA-IR ,insulin secretion index and maternal serum cortisol level were significantly increased in GDM group [(19 .95 ± 1 .05) mU/L vs .(12 .93 ± 1 .50) mU/L ,4 .54 ± 0 .67 vs .2 .87 ± 0 .43 , 80 .55 ± 6 .18 vs .53 .15 ± 5 .58 ,(1110 .00 ± 40 .91) nmol/L vs .(934 .1 ± 45 .92) nmol/L ,P<0 .05)] ,but there were no significant differences were found in fasting blood glucose and cord blood cortisol (P>0 .05) .The distribution of 11β-HSD1 in the placenta was distributed in the outer layer of villous syncytiotrophoblast ,villous interstitial and dry villi .The expression of 11β-HSD2 was con-centrated in the outer layer of villous syncytiotrophoblast .Real time-PCR and Western blot results showed that the expression of 11β-HSD1 mRNA and protein in placenta of GDM group was significantly lower than that of NGT group (0 .56 ± 0 .09 vs .1 .36 ± 0 .36 ,0 .27 ± 0 .07 vs .1 .00 ± 0 .01 ,P< 0 .05 ) ,11β-HSD2 mRNA was significantly higher than NGT group (5 .17 ± 1 .02 and 1 .21 ± 0 .34 respectively ,P<0 .05) ,but no significant difference was found in protein level (P>0 .05) .Conclusion The differenti-al expression of 11β-HSD1 and 11β-HSD2 in placenta of gestational diabetes mellitus can avoid the maternal poor pregnancy envi-ronment ,but will cause long-term harm to the fetus .
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Aim To identify alteration in key molecular components related to memory formation and insulin signaling in the hippocampus after rosiglitazone was in-jected into the ob/ob mice to test whether cognitive dysfunction was pharmacologically reversed by regula-tion of rosiglitazone. Methods The age-matched mice were divided into three groups ( n=18 ): Saline-trea-ted WT mice ( WT-Saline);Saline-treated ob/ob mice ( ob/ob-Saline) and RSG-treated ob/ob mice ( ob/ob-RSG) through intraperitoneal injection of rosiglitazone ( RSG) . The random glucose levels were measured for 10 days during the intraperitoneal injection period. No-vel object recognition was performed before mice were sacrificed. Western blot was implemented to evaluate the following proteins: BACE1, p-Tau, p-IRS1,IRS1, p-Akt and Akt in hippocampal tissues. The Aβ1-40 levels were detected by ELISA Kit. Results The random blood glucose levels were significantly re-duced in ob/ob-RSG compared with ob/ob-saline. RSG treatment led to an increase in hippocampus-de-pendent cognition of ob/ob mice according to the novel object recognition. The proteins levels of BACE1, p-Tau and Aβ were lowered in RSG-treated ob/ob mice. Furthermore, RSG treatment up-regulated hippocampal p-IRS1/IRS1 and p-Akt/Akt ratio. Conclusion Ros-iglitazone ameliorates cognitive deficits in ob/ob mice through up-regulating insulin signaling pathways in the hippocampus.
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<p><b>OBJECTIVE</b>To determine the effects of probucol on serum parameters and liver histopathology in rats with non-alcoholic steatohepatitis (NASH) and explore the mechanisms.</p><p><b>METHODS</b>Forty male Sprague-Dawley rats were randomly assigned into 4 equal groups, namely the normal control group (NC group) with a standard feeding, high-fat diet group (HD group) fed with a high-fat diet, probucol (500 mg/kg daily) control group (NP group) fed with standard diet, and probucol group fed with a high-fat diet (HP group). After 15 weeks of feeding, the rats were euthanized for histopathological inspection of the liver with HE staining and detection of farnesoid X receptor (FXR), SHP and SREBP-1C expressions using semi-quantitative RT-PCR and Western blotting.</p><p><b>RESULTS</b>After the 15-week feeding, the rats in HP group had significantly lower levels of serum ALT, AST, cholesterol, bile acid, and free fatty acid than those in HD group (P<0.01 or 0.05). Compared with the normal control group, high-fat diet feeding resulted in significantly decreased mRNA and protein levels of FXR and SHP (P<0.05) and significantly increased SREBP-1C level (P<0.05). These high-fat diet-induced gene expression changes were reversed by probucol intervention (P<0.05).</p><p><b>CONCLUSION</b>Probucol treatment has beneficial effects on serum parameters, hepatic steatosis, and lobular inflammation in high-fat diet-induced NASH possibly by up-regulating FXR expression.</p>