Ursolic acid ameliorates pancreatic β-cell injury in type Ⅰ diabetic rats via the TLR4/NF-κB pathway and Th17/Treg cell homeostasis
Objective To investigate the effects of ursolic acid(UA)on the TLR4/NF-κB signaling pathway and Th17/Treg cells in type 1 diabetes mellitus(T1DM)rats.Methods T1DM rat models were established by intraperitoneal injection of streptozotocin(STZ)and randomly divided into blank(Control),Model,metformin(MET),and UA groups.General conditions,such as body weight and blood glucose,were recorded,and peripheral blood and pancreatic tissues were collected after 6 weeks of gavage to assess insulin treatment.Immunohistochemistry was used to observe pathological changes in pancreatic tissues.Horseshoe crab reagent was used to assess changes in serum lipopolysaccharide(LPS)content.qRT-PCR was used to measure expression of pancreatic TLR4,MyD88,IκBα,and NF-κB p65 mRNAs,and mRNA expression of transcription factors RORγt and Foxp3.Western blot was used to assess pancreatic TLR4,MyD88,IκBα,NF-κB p65,RORγt,and Foxp3.Flow cytometry was used to assess changes Th17/Treg cell ratio in peripheral blood.ELISA were used to measure serum contents of TNF-α,IL-6,and IL-1 β.Results After STZ-induced diabetic rats were treated by gavage for 6 weeks,compared with the Model group,the fasting blood glucose of rats in MET and UA groups was significantly decreased and their body weights were increased.Inflammatory infiltration of pancreatic islet β-cells was reduced.Expression of TLR4,MyD88,IκBα,NF-κB p65,and RORγt mRNAs and proteins was significantly decreased.LPS content was significantly decreased.IκBα and Foxp3 mRNA and protein expression was significantly increased.The Th17/Treg ratio was significantly decreased,and TNF-α,IL-6,and IL-1 β contents were significantly decreased.Conclusions UA improves the symptoms of rats by reducing the LPS shift,inhibiting the TLR4/NF-κB pathway,down-regulating RORγt expression,and up-regulating Foxp3 expression to correct the imbalance in the Th17/Treg cell ratio in T1DM rats.
type 1 diabetes mellitusursolic acidTLR4/NF-κB pathwayTh17/Treg cells
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