ABSTRACT
The present study aimed to explore the neuroprotective effect and possible mechanisms of rhGLP-1 (7–36) against transient ischemia/reperfusion injuries induced by middle cerebral artery occlusion (MCAO) in type 2 diabetic rats. First, diabetic rats were established by a combination of a high-fat diet and low-dose streptozotocin (STZ) (30 mg/kg, intraperitoneally). Second, they were subjected to MCAO for 2 h, then treated with rhGLP-1 (7–36) (10, 20, 40 µg/kg i.p.) at the same time of reperfusion. In the following 3 days, they were injected with rhGLP-1 (7–36) at the same dose and route for three times each day. After 72 h, hypoglycemic effects were assessed by blood glucose changes, and neuroprotective effects were evaluated by neurological deficits, infarct volume and histomorphology. Mechanisms were investigated by detecting the distribution and expression of the nuclear factor erythroid-derived factor 2 related factor 2 (Nrf2) in ischemic brain tissue, the levels of phospho-PI3 kinase (PI3K)/PI3K ratio and heme-oxygenase-1 (HO-l), as well as the activities of superoxide dismutase (SOD) and the contents of malondialdehyde (MDA). Our results showed that rhGLP-1 (7–36) significantly reduced blood glucose and infarction volume, alleviated neurological deficits, enhanced the density of surviving neurons and vascular proliferation. The nuclear positive cells ratio and expression of Nrf2, the levels of P-PI3K/PI3K ratio and HO-l increased, the activities of SOD increased and the contents of MDA decreased. The current results indicated the protective effect of rhGLP-1 (7–36) in diabetic rats following MCAO/R that may be concerned with reducing blood glucose, up-regulating expression of Nrf2/HO-1 and increasing the activities of SOD.
Subject(s)
Animals , Rats , Blood Glucose , Brain , Diet, High-Fat , Hypoglycemic Agents , Infarction , Infarction, Middle Cerebral Artery , Malondialdehyde , Neurons , Neuroprotective Agents , Phosphotransferases , Reperfusion , Reperfusion Injury , Streptozocin , Superoxide DismutaseABSTRACT
Objective: To establish a method to detect the content of propylene glycol in the recombinant human glucagon-like peptide-1 (rhGLP-1) (7-36) injection by gas chromatography (GC). Methods: GC was performed using a quartz capillary column (30 m×320 μm,0.5 μm) with the mobile phase of N2 and inlet temperature of 230℃ at the flow rate of 1ml/min and column temperature of 250 ℃, the injection volume was 1μl. Results: The calibration curve was linear within the range of 0.5-1.5 mg/ml, r=0.9991. The average recovery rate was 100.2%; under different chromatographic conditions, the method had good stability, RSD was less than 2.0%. Conclusion: This method is simple, accurate and reproducible, and can be applied in the determination of propylene glycol content in rhGLP-1 (7-36) injection.
ABSTRACT
Objective To establish a method to detect the content of propylene glycol in the recombinant human glucagon-like peptide-1(rhGLP-1)(7-36) injection by gas chromatography(GC). Methods GC was performed using a quartz capillary column (30 m ×320 μm,0.5 μm) with the mobile phase of N2 and inlet temperature of 230℃ at the flow rate of 1ml/min and column temperature of 250 ℃, the injection volume was 1μl. Results The calibration curve was linear within the range of 0.5-1.5 mg/ml, r=0.9991. The average recovery rate was 100.2%; under different chromatographic conditions, the method had good stability, RSD was less than 2.0%. Conclusion This method is simple, accurate and reproducible, and can be applied in the determination of propylene glycol content in rhGLP-1(7-36) injection.