Irbesartan ameliorates cardiac inflammation in type 2 diabetic db/db mice / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the protective effects of irbesartan against cardiac inflammation associated with diabetes and obesity in the db/db mouse model of type 2 diabetes and explore the underlying mechanisms.</p><p><b>METHODS</b>Twenty- four 10-week-old diabetic db/db mice were equally randomized into irbesartan treatment (50 mg/kg per day) group and model group, using 12 nondiabetic littermates (db/+) as the controls, The mice were treated with irbesartan or saline vehicle for 16 consecutive weeks, after which the heart pathology was observed and the heart weight, body weight, and serum levels of fasting blood glucose (FBG), total cholesterol(TC), and triglycerides(TG) were measured. The expression of nuclear factor-kappaB (NF-κB) p65 in the myocardium was assessed with immunohistochemistry, the protein levels of P-IκBα ,IκBα and β-actin were analyzed with Western blotting, and the pro-inflammatory cytokines IL-6 and TNF-α mRNA were detected using quantitative real-time PCR (qPCR).</p><p><b>RESULTS</b>Compared with db/+ mice, the saline-treated db/db mice developed obesity, hyperglycemia and hyperlipidemia (P<0.01). Histopathological examination of the heart tissue revealed inflammatory cell infiltration, increased myocardial interstitium and disorders of myocardial fiber arrangement. The diabetic mice showed increased P-IαBα and decreased IκBα protein levels, enhanced activity and expression of NF-κB in the hearts, and increased mRNA expression of IL-6 and TNF-α in the myocardium. These abnormalities were all associated with increased inflammatory response. Treatment with irbesartan improved the heart architecture and attenuated high glucose-induced inflammation in the diabetic mice.</p><p><b>CONCLUSION</b>Treatment with irbesartan attenuates cardiac inflammation in type 2 diabetic db/db mice, and this effect was probably associated with the suppression of cardiac angiotensin II and NF-κB signaling pathway.</p>

Lead impairs ability of learning and memory and affects expression of synaptosomal-associated protein-25 in hippocampus of offspring / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To find the effects of lead taken by pregnant mice on learning and memory and the expression of synaptosomal-associated protein (SNAP)-25 mRNA and protein, in order to reveal the mechanism of neurotoxicity induced by lead.</p><p><b>METHODS</b>Lead exposure was conducted through freely drinking the corresponding lead acetate solutions with dosages of 0.3, 1.0, 3.0 g/L respectively. Each group was composed of 10 mice. 7, 14 and 21 days after their birth. The lead contents in blood and hippocampus of the offspring were determined. At the 21st day the expression of SNAP-25 mRNA and protein in hippocampus of all the offspring in various dosages groups were determined by RT-PCR and immunohistochemistry assay.</p><p><b>RESULTS</b>The lead contents in blood and hippocampus of various lead exposed groups were significantly higher than those of the control group (P < 0.05). The lead levels in blood and hippocampus changed accordingly to the days of growth. In Water Morris Maze experiment, the result of 0.3 g/L group was not significantly different from that of the control group (P > 0.05), however, the results of 1.0, 3.0 g/L groups (5.89 ± 0.54, 9.53 ± 1.03) were significantly different from those of the control group (1.73 ± 0.07) (P < 0.05, P < 0.01). The expression of SNAP-25 mRNA and protein was lower in lead exposed groups than that of the control group (P < 0.05).</p><p><b>CONCLUSION</b>Maternal lead exposure may induce the damage in the ability of learning and memory of the offspring. The neurotoxicity of lead may be induced by decreasing the expression of SNAP-25 mRNA and protein so as to affect the release of neurotransmitter from presynaptic terminal resulted in nerve damages.</p>

Differences in the response to sepsis between C57BL/6 and BALB/c mice / 南方医科大学学报

<p><b>OBJECTIVE</b>To compare the responses to sepsis between C57BL/6 and BALB/c mice.</p><p><b>METHODS</b>Thirty C57BL/6 mice and 30 BALB/c mice were randomized into sham-operated group and sepsis group (n=15). Sepsis model was established by cecal ligation puncture (CLP) in the mice, and 6 h after the operation, 5 mice from each group were selected randomly for cytokine detection including IL-1beta, IL-2, IL-4, IL-5, IL-10, GM-CSF, IFN-gamma and TNF-alpha by Bio-plex. The other 10 mice in each group were used for survival analysis.</p><p><b>RESULTS</b>The survival rates of BALB/c and C57BL/6 mice were both 100% in one week after the sham operation, but lowered to 10% and 50% in one week after CLP, respectively. The survival rate of C57BL/6 mice was significantly lower than that of BALB/c mice (P<0.05). After CLP, C57BL/6 mice showed significantly greater IL-4, TNF-alpha and IL-10 production than the sham-operated mice, but the concentrations of the 8 cytokines in BALB/c mice after CLP showed no significant increment.</p><p><b>CONCLUSION</b>Compared with BALB/c mice, C57BL/6 strain mouse is more sensitive to sepsis.</p>