Matrine promotes skin wound healing and angiogenesis through Hippo signaling pathway in rats
Objective To investigate the effect of matrine(MT)on skin wound healing and its possible mechanism.Methods A total skin excision trauma model was successfully constructed in 48 rats.The model rats were randomly divided into a negative control group(Model group,smeared with 100 μL isotonic saline),a posi-tive drug group(PD group,smeared with 100 μL Jing Wan Hong ointment),a matrine group(MT group,100 μL matrine mixed solution with a concentration of 200 ng/mL),and a matrine +vertepor-fin group(MT+VP group,intraperitoneal injection of 100 mg/kg verteporfin after applying 100 μL matrine mixture),with 12 rats in each group.Each group was administered once daily for 7 d.The wound healing rate,pathological tissue damage,proportion of CD31 positively stained cells,and serum IL-6,TNF-α,and IL-1βlevels were compared among the groups.Western blot was performed to de-tect the expression of Hippo pathway-related proteins.Results On the 3rd,7th,and 14th day after modeling,compared with the wound healing rates of the model group[(14.02±1.87)%,(36.23±3.62)%,(65.53±3.85)%],PD group[(21.36±2.51)%,(61.86±3.13)%,(94.26±0.26)%]and MT group[(21.57±2.24)%,(54.35±3.66)%,(94.18±3.13)%]were signifi-cantly increased(P＜0.05);Compared with the MT group,the wound healing rate of the MT+VP group[(18.35±2.03)%,(43.68±3.54)%,(74.26±3.55)%]was significantly decreased(P＜0.05).7 days after modeling,compared with the model group(186.75±18.53,85.73±10.15,57.96±5.85),the levels of IL-1β,IL-6 and TNF-α in PD group(89.75±9.75,43.12±5.75,8.76±1.13)and MT group(92.57±23.62,46.62±6.54,12.36±1.06)were significantly decreased(P＜0.05),the per-centage of CD31 positive staining cells,the phosphorylation levels of MST1,LAST1 and YAP proteins were significantly increased(P＜0.05),while the nuclear translocation of YAP was significantly decreased(P＜0.05).Compared with the MT group,the MT+VP group had significant increases in the levels of IL-1β,IL-6,and TNF-α,a significant reduction in the percentage of CD31 positive stai-ning cells,a significant reduction in the phosphorylation levels of MST1,LAST1 and YAP proteins,and a significant increase in the nuclear translocation of YAP(P＜0.05).Compared with the complete wound healing time[(26.33±0.94)d]and scar thickness[(0.58±0.11)mm]of the Model group,PD group[(19.50±0.82)d,(0.24±0.04)mm]and MT group[(19.00±0.50)d,(0.25±0.04)mm]were significantly decreased(P＜0.05).Compared with the MT group,the complete wound healing time[(22.33±0.94)d]and scar thickness[(0.41±0.04)mm]in the MT+VP group were significantly increased(P＜0.05).Conclusion Matrine was able to accelerate skin wound healing in rats with total skin excision trauma by inhibiting inflammatory re-sponse and promoting angiogenesis,and this process may involve the activating effect of Matrine on the Hippo-Yap pathway.
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