Interleukin-4(IL-4) has a protective effect against cerebral ischemia/reperfusion injury. Animal experiments have shown that IL-4 improves the short-and long-term prognosis of neurological function. The Akt(also calle...Interleukin-4(IL-4) has a protective effect against cerebral ischemia/reperfusion injury. Animal experiments have shown that IL-4 improves the short-and long-term prognosis of neurological function. The Akt(also called protein kinase B, PKB)/glycogen synthase kinase-3β(Akt/GSK-3β) signaling pathway is involved in oxidative stress, the inflammatory response, apoptosis, and autophagy. However, it is not yet clear whether the Akt/GSK-3β pathway participates in the neuroprotective effect of IL-4 against cerebral ischemia/reperfusion injury. In the present study, we established a cerebral ischemia/reperfusion mouse model by middle cerebral artery occlusion for 60 minutes followed by a 24-hour reperfusion. An IL-4/anti-IL-4 complex(10 μg) was intraperitoneally administered 30 minutes before surgery. We found that administration of IL-4 significantly alleviated the neurological deficits, oxidative stress, cell apoptosis, and autophagy and reduced infarct volume of the mice with cerebral ischemia/reperfusion injury 24 hours after reperfusion. Simultaneously, IL-4 activated Akt/GSK-3β signaling pathway. However, an Akt inhibitor LY294002, which was injected at 15 nmol/kg via the tail vein, attenuated the protective effects of IL-4. These findings indicate that IL-4 has a protective effect on cerebral ischemia/reperfusion injury by mitigating oxidative stress, reducing apoptosis, and inhibiting excessive autophagy, and that this mechanism may be related to activation of the Akt/GSK-3β pathway. This animal study was approved by the Animal Ethics Committee of Renmin Hospital of Wuhan University, China(approval No. WDRY2017-K037) on March 9, 2017.展开更多
OBJECTIVE: To explore the molecular mechanism underpinning the action by investigating its effect on glycogen content and AKT(also known as protein kinase B)/glycogen synthase kinase 3β(GSK-3β) pathway in the liver ...OBJECTIVE: To explore the molecular mechanism underpinning the action by investigating its effect on glycogen content and AKT(also known as protein kinase B)/glycogen synthase kinase 3β(GSK-3β) pathway in the liver of rats with type 2 diabetic induced by high-fat diet.METHODS: The rat model of type 2 diabetes was induced by high-fat diet and multiple low-dose streptozotocin injection. Diabetic rats were divided into five groups: the model control group, the Metformin group, spleen-kidney supplementing formula groups of low, medium and high doses. Fasting blood glucose(FBG) levels were measured before treatment and every two weeks during treatment.After the treatment, oral glucose tolerance test was performed, and hemoglobin A1c (HbA1c) and C-peptide were measured to assess the formula's effect on glucose metabolism and insulin resistance. The protein expression levels of AKT, GSK-3βand their phosphorylated forms in the liver were also measured to study the formula's role in insulin signaling pathway.RESULTS: Spleen-kidney supplementing formula significantly relieved the symptoms of polydipsia,polyuria and weight loss in type 2 diabetic rats, reduced FBG and HbA1c levels, increased glycogen content, and improved insulin sensitivity. The anti-diabetic effects of spleen-kidney supplementing formula are dose dependent. It also increased the total AKT protein level and the GSK-3β phosphorylation in the liver of type 2 diabetic rats.CONCLUSION: Spleen-kidney supplementing formula has hypoglycemic effect and relieves insulin resistance by enhancing AKT/GSK-3β signaling pathway in the liver of type 2 diabetic rats.展开更多
基金supported by the National Natural Science Foundation of China,Nos.81901994(to BZ)and 81571147(to XXX)the Natural Science Foundation of Hubei Province,China,No.2019CFC847(to WWG)the Fundamental Research Funds for the Central Universities,China,No.2042018kf0149(to ML)
文摘Interleukin-4(IL-4) has a protective effect against cerebral ischemia/reperfusion injury. Animal experiments have shown that IL-4 improves the short-and long-term prognosis of neurological function. The Akt(also called protein kinase B, PKB)/glycogen synthase kinase-3β(Akt/GSK-3β) signaling pathway is involved in oxidative stress, the inflammatory response, apoptosis, and autophagy. However, it is not yet clear whether the Akt/GSK-3β pathway participates in the neuroprotective effect of IL-4 against cerebral ischemia/reperfusion injury. In the present study, we established a cerebral ischemia/reperfusion mouse model by middle cerebral artery occlusion for 60 minutes followed by a 24-hour reperfusion. An IL-4/anti-IL-4 complex(10 μg) was intraperitoneally administered 30 minutes before surgery. We found that administration of IL-4 significantly alleviated the neurological deficits, oxidative stress, cell apoptosis, and autophagy and reduced infarct volume of the mice with cerebral ischemia/reperfusion injury 24 hours after reperfusion. Simultaneously, IL-4 activated Akt/GSK-3β signaling pathway. However, an Akt inhibitor LY294002, which was injected at 15 nmol/kg via the tail vein, attenuated the protective effects of IL-4. These findings indicate that IL-4 has a protective effect on cerebral ischemia/reperfusion injury by mitigating oxidative stress, reducing apoptosis, and inhibiting excessive autophagy, and that this mechanism may be related to activation of the Akt/GSK-3β pathway. This animal study was approved by the Animal Ethics Committee of Renmin Hospital of Wuhan University, China(approval No. WDRY2017-K037) on March 9, 2017.
基金Supported by Key Program of Science and Technology Research of Higher Education Institutions in Hebei Province(No.Zd2018215)Doctoral Scientific Research Fund of North China University of Science and Technology(No.BS2017064)
文摘OBJECTIVE: To explore the molecular mechanism underpinning the action by investigating its effect on glycogen content and AKT(also known as protein kinase B)/glycogen synthase kinase 3β(GSK-3β) pathway in the liver of rats with type 2 diabetic induced by high-fat diet.METHODS: The rat model of type 2 diabetes was induced by high-fat diet and multiple low-dose streptozotocin injection. Diabetic rats were divided into five groups: the model control group, the Metformin group, spleen-kidney supplementing formula groups of low, medium and high doses. Fasting blood glucose(FBG) levels were measured before treatment and every two weeks during treatment.After the treatment, oral glucose tolerance test was performed, and hemoglobin A1c (HbA1c) and C-peptide were measured to assess the formula's effect on glucose metabolism and insulin resistance. The protein expression levels of AKT, GSK-3βand their phosphorylated forms in the liver were also measured to study the formula's role in insulin signaling pathway.RESULTS: Spleen-kidney supplementing formula significantly relieved the symptoms of polydipsia,polyuria and weight loss in type 2 diabetic rats, reduced FBG and HbA1c levels, increased glycogen content, and improved insulin sensitivity. The anti-diabetic effects of spleen-kidney supplementing formula are dose dependent. It also increased the total AKT protein level and the GSK-3β phosphorylation in the liver of type 2 diabetic rats.CONCLUSION: Spleen-kidney supplementing formula has hypoglycemic effect and relieves insulin resistance by enhancing AKT/GSK-3β signaling pathway in the liver of type 2 diabetic rats.
