Exploratiom Of The Mechanism Of Kuiyuling Ointment In Promoting Wound Healing Of Diabetic Rats Based On AGEs/RAGE Pathway

Objective:To study the effects of Kuiyuling ointment on the wounds of diabetic rats,and to explore its mechanism based on AGEs/RAGE.Methods:Except for the normal group,40 male SPF rats were fed with high-fat and high-sugar diet and injected with STZ to establish diabetic model.They were randomly divided into model group,burn ointment group and Kuyuling group.After the wound was established,each group take corresponding intervention measures.Then observe the wound on the 7^th and14^th day after treatment,calculate the wound healing rate,and observe the pathological changes of wound tissue by HE,test the expression levels of IL-1,TNF-α,and VEGF in serum of rats by ELISA,and test the expression levels of AGEs,RAGE in wound tissue of rats by WB.Results:1.On the the 7^th and 14^th day of treatment,compared with the normal group,the healing rate of the model group was lower（P<0.05）,and the granulation tissue grew slowly and had poor activity.Histopathological observation showed that the inflammatory infiltration,necrosis and other pathological changes of the wound tissue in the model group were more serious,and the recovery was slow.Compared with the model group,the burn cream group and the Kuiyuling group had a higher wound healing rate（P<0.05）,a faster growth of granulation tissue,and a lighter degree of wound tissue lesions and faster recovery.There was no significant difference in the wound healing rate between the burn cream group and the Kuyuling group（P>0.05）.However,on the 14^th day of treatment,the pathological changes of the wound tissue in the Kuyuling group were lighter and closer to the physiological structure.2.On the 7th and 14th day after the treatment,the expressions of IL-1 and TNF-αin the model group showed an upward trend,which were higher than those in the normal group（P<0.05）,but the expression of VEGF showed a downward trend,which was lower than that in the normal group（P<0.05）.On the 7^th day of treatment,there were no significant differences in the serum levels of IL-1,TNF-αand VEGF between the burn cream group and the model group（P>0.05）.On the 14th day of treatment,the serum levels of IL-1 and TNF-αin the burn cream group and the Kuiyuling group were decreased,which were lower than those in the model group（P<0.05）.The serum levels of VEGF were increased,which were higher than those in the model group（P<0.05）.But there was no significant difference between the burn cream group and the Kuiyuling group（P>0.05）.3.On the 7th and 14th day of treatment,the expression levels of AGEs,RAGE in the model group were higher than those in the normal group（P<0.05）.The protein expressions of AGEs,RAGE in the burn cream group and the Kuiyuling group showed a downward trend with the increase of treatment time,and were lower than those in the model group（P<0.05）.The protein expressions of AGEs,RAGE in the Kuiyuling group were lower than those in the burn cream group（P<0.05）.Conclusion:1.Compared with conventional wounds,diabetic wounds have more severe pathological changes such as inflammatory response and slow healing.The mechanism may be related to the expression of related proteins and cytokines in AGEs/RAGE pathway.2.Kuiyuling ointment can promote diabetic wound healing,and its effect is similar to that of Meibao ointment.3.Kuiyuling ointment can regulate the transcription and release of downstream cytokines in the pathway,reduce inflammatory response,reconstruct wound microcirculation,and promote diabetic wound healing by cutting the expression of related proteins in AGEs/RAGE pathway.The regulatory effects of Kuiyuling ointment and moist burn ointment on cytokines mainly appeared in the late stage of treatment.At the same time,the inhibitory effect of Kuiyuling ointment on the above pathways is stronger than that of Meibao ointment.