الملخص
OBJECTIVES@#To evaluate the effect of echinacoside (ECH) on cognitive dysfunction in post cerebral stroke model rats.@*METHODS@#The post stroke cognitive impairment rat model was created by occlusion of the transient middle cerebral artery (MCAO). The rats were randomly divided into 3 groups by a random number table: the sham group (sham operation), the MCAO group (received operation for focal cerebral ischemia), and the ECH group (received operation for focal cerebral ischemia and ECH 50 mg/kg per day), with 6 rats in each group. The infarct volume and spatial learning were evaluated by triphenyl tetrazolium chloride staining and Morris water maze. The expression of α7nAChR in the hippocampus was detected by immunohistochemistry. The contents of acetylcholine (ACh), malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD), activities of choline acetyltransferase (ChAT), acetylcholinesterase (AChE), and catalase (CAT) were evaluated by enzyme linked immunosorbent assay. The neural apoptosis and autophagy were determined by TUNEL staining and LC3 staining, respectively.@*RESULTS@#ECH significantly lessened the brain infarct volume and ameliorated neurological deficit in infarct volume and water content (both P<0.01). Compared with MCAO rats, administration of ECH revealed shorter escape latency and long retention time at 7, 14 and 28 days (all P<0.01), increased the α7nAChR protein expression, ACh content, and ChAT activity, and decreased AChE activity in MCAO rats (all P<0.01). ECH significantly decreased MDA content and increased the GSH content, SOD, and CAT activities compared with MCAO rats (all P<0.05). ECH suppressed neuronal apoptosis by reducing TUNEL-positive cells and also enhanced autophagy in MCAO rats (all P<0.01).@*CONCLUSION@#ECH treatment helped improve cognitive impairment by attenuating neurological damage and enhancing autophagy in MCAO rats.
الموضوعات
Animals , Rats , Acetylcholinesterase , Autophagy , Brain Ischemia/metabolism , Cerebral Infarction , Cognitive Dysfunction/drug therapy , Glutathione/metabolism , Glycosides , Infarction, Middle Cerebral Artery/drug therapy , Neuroprotective Agents/therapeutic use , Rats, Sprague-Dawley , Reperfusion Injury/drug therapy , Stroke/drug therapy , Superoxide Dismutase/metabolism , alpha7 Nicotinic Acetylcholine Receptorالملخص
Objective To explore the effect of salsalate on the glucose metabolism of obese mice induced with high fat diet (HFD). Methods Eight week-old male C57BL/6J mice were fed with HFD in combination with 0.5% of salsalate (SAL group, n=5) or normal saline (control group, n=5) for 40 days. The effect of salsalate on serum glucose level was examined by glucose tolerance test (GTT) and insulin tolerance test (ITT). The expressions of endoplasmic reticulumn related proteins, including CCAAT/enhancer-binding protein homologous protein (CHOP), endoplasmic reticulum-localized DnaJ 4 (ERDJ4), glucose regulated protein (GRP)78 and GRP94, were measured by qPCR and Western blotting. Results The random blood glucose level of obese mice were significantly lower in the SAL group than that in the control group (P0.05), and GTT showed that the mice in the SAL group had better glucose tolerance. However, there was no significant difference in fasting insulin level between the two groups. ITT showed there was no difference in the change of blood glucose after insulin stimulation between the two groups. The mRNA expressions of GRP78 and GRP94 and protein expressions of CHOP, ERDJ4, GRP78 and GRP94 were significantly lower in the SAL group than those in the control group (P0.05 or P0.01). Conclusion Salsalate can alleviate the hyperglycemia of obese mice induced with HFD by inhibiting endoplasmic reticulum stress, and the effect is independent of the insulin secretion.