OBJECTIVE To observe the effect of Shixiang plaster on promoting the wound healing of diabetic foot ulcer.

METHODS Totally 50 male SPF grade SD rats were prepared to establish the diabetic models by feeding with high glucose and high fat forage and intraperitoneal injection of streptozotocin, the rats models that were established successfully were randomly divided into the model group, the Shixiang plaster group and the Kangfuxin solution group. The models of diabetic ulcers were established. The Shixiang plaster group was treated with external Shixiang plaster, the Kangfuxin solution group was given external Kangfuxin solution, and the model group was treated with coverage with sterile gauze. The wound healing status of the rats was observed, the wound tissues were collected for bacterial culture and hematoxylin-eosin (HE) staining after drug administration for 14 and 28 days, respectively. The expression levels of nuclear factor-red cell-2-related factor 2 (Nrf-2), heme oxygenase-1 (HO-1), tumor necrosis factor-α(TNF-α), interleukin-6(IL-6) and vascular endothelial growth factor (VEGF) were detected by immunohistochemistry(IHC), the expression levels of Nrf-2 and HO-1 were detected with the use of Western Blot, and the levels of serum malondialdehyde (MDA), superoxide dismutase (SOD) and reactive oxygen species (ROS) were detected by enzyme-linked immunosorbent assay (ELISA).

RESULTS After the drug administration for 14 and 28 days, the wound healing rates of the Shixiang plaster group were (62.15±3.82)% and (81.68±3.83)%, respectively, higher than (47.14±2.80)% and(69.96±6.49)% of the Kangfuxin solution group and (29.14±9.52)% and (57.91±6.63)% of the model group, and there were significant differences (F=21.716, 12.626, P=0.002, 0.007). The bacterial colony counts of the Shixiang plaster group were less than those of the Kangfuxin solution group and the model group after the drug administration for 14 and 28 days(P<0.05). The result of HE staining showed that the Shixiang plaster group had a better wound healing. The result of IHC indicated that the expression levels of Nrf-2, HO-1 and VEGF of the Kangfuxin solution group and the Shixiang plaster group were up-regulated after the drug administration for 28 days, while the expression levels of TNF-α and IL-6 were down-regulated. The expression levels of Nrf-2 and HO-1 proteins of the Shixiang plaster group were higher than those of the Kangfuxin solution group and the model group after the drug administration for 14 and 28 days, the levels of serum MDA and ROS of the Shixiang plaster group were lower than those of the Kangfuxin solution group and the model group, and the serum SOD level of the Shixiang plaster group was higher than that of the model group (P<0.05).

CONCLUSIONS Shixiang plaster can effectively promote the wound healing of the rats with diabetic foot ulcers and reduce the bacterial colony counts of wound surfaces. The mechanism may be associated with the alleviation of oxidative stress injury by mediating the Nrf-2/HO-1 signaling pathways, promotion of angiogenesis and inhibition of excessive inflammatory reactions.