| Objective: To investigate the possible mechanism of Sheng Ji Chuangyu ointment based on p38 MAPK signaling pathway in the treatment of chronic skin ulcers by observing the effect of Sheng Ji Chuangyu ointment on wound healing in rats with chronic skin ulcers,and to lay the experimental foundation for the clinical application of Sheng Ji Chuangyu ointment.Methods: Thirty six SD(Sprague Dawley)rats were selected,and they were randomly grouped into 8 rats in the control group and 28 rats in the modeling group.The rat models of chronic skin ulcers were prepared by using a combination of skin defect plus bacterial infection and hormonal intervention.The specific method was as follows.First,two 1.5cm diameter full skin lesion wounds were made on the upper lumbar vertebrae of the rat’s back.Except for rats in the normal group,all rats were inoculated with Staphylococcus aureus solution(0.5 ml/100 g)and hydrocortisone acetate(2 mg/100 g)intraperitoneally for seven consecutive days.The rats in the control group were only treated with full skin defect wounds without drug injection and bacterial infection.In the modeling group,24 rats were modeled successfully and randomly divided into the modeling group,the Sheng Ji Chuangyu ointment group and the MEBO group,with 8 rats in each group.The drug treatment was started on the 1st day after successful modeling.The control group and the model group were treated with saline gauze,the MEBO group was treated with MEBO gauze,and the Sheng Ji Chuangyu ointment group was treated with Sheng Ji Chuangyu ointment gauze twice a day.The treatment lasted for one week.The general condition and wound growth of each group were observed and recorded;The wound area of each group of rats was measured on day 3 and day 7 to calculate the wound healing rate.The wound tissues were gathered for following HE staining,ELISA,RT-PCR and Western blotting.Results:1.The general condition and wound growth of the rats in the MEBO group and the Sheng Ji Chuangyu ointment group were better than those in the model group on the 3rd and 7th days of administration.Compared with the MEBO group,the wound healing rate of the Sheng Ji Chuangyu ointment group was less exudate,more obvious epithelial crawling,and better healing.2.On the third day of administration,the wound healing rate was significantly higher in the MEBO group and the Sheng Ji Chuangyu ointment group than in the model group(P<0.05).And on the seventh day,compared with the model group,the wound healing rate was visably higher in the Sheng Ji Chuangyu ointment and MEBO groups(P<0.01),and the wound healing rate was higher in the Sheng Ji Chuangyu ointment group than in the MEBO group(P<0.05).3.On the 3rd and 7th days of administration,the TNF-α and IL-6 levels in rat traumatic tissues in the MEBO group and the Sheng Ji Chuangyu ointment group declined markedly than the model group(P<0.05);On the 7th day of administration,the levels of TNF-αand IL-6 contents in the Sheng Ji Chuangyu ointment group were obviously lower than in the MEBO group(P<0.05).4.On the 3rd and 7th days of treatment,the expression of p38 mRNA and MK2 mRNA in the group of Sheng Ji Chuangyu ointment reduced remarkably compared with the model group(P<0.01),and the expressions of p38 mRNA and MK2 mRNA were significantly lower in the Sheng Ji Chuangyu ointment group than that in the MEBO group at day 7(P<0.05).5.On day 3,the p-p38/ p38 ratio of rats in the Sheng Ji Chuangyu ointment was notably lower than the MEBO and model group(P<0.05),and there was no clear distinction in the p-MK2/MK2 ratio between the three groups.On day 7,the p-p38/p38 and p-MK2/MK2 ratios of the rats in the Sheng Ji Chuangyu ointment and MEBO groups declined markedly than the model group(P<0.05),and the decline was more obvious in the Sheng Ji Chuangyu ointment group than the MEBO group(P<0.05).Conclusions:1.The rat model of chronic skin ulcers can be successfully established by the modeling method of "skin defect plus bacterial infection and hormonal intervention".2.The wound healing rate of chronic skin ulcers in rats can be improved by the Sheng Ji Chuangyu ointment,and the wound healing can be promoted.3.The Sheng Ji Chuangyu ointment can decrease the expression levels of TNF-α and IL-6 in the wounds of chronic skin ulcers in rats,thus alleviating the traumatic inflammatory response.4.The p38 mRNA and MK2 mRNA gene expression and p-p38/p38 and p-MK2/MK2 ratios in the traumatic tissue of rats with chronic skin ulcers can be reduced by the Sheng Ji Chuangyu ointment.5.The Sheng Ji Chuangyu ointment may play a role in the treatment of chronic skin ulcers by inhibiting the P38 MAPK signaling pathway. |
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