Effects Of ALA-PDT And LED Red Light On Non-infectious And Infectious Wounds On The Back Of T1DM Rats

Background and Objective:Diabetic foot ulcer is a disabling complication of diabetes.It is difficult to treat and has a high recurrence rate.Patients have low quality of life and poor psychosocial adaptability.The disease occupies a large number of diabetes medical resources worldwide.Wound healing is a physiological process with precise regulation and complex procedures.The most significant reason for the delayed healing of diabetic foot ulcers may be that the persistent inflammatory response in the wound area hinders the formation of granulation tissue,and the persistent inflammatory response may be caused by vascular injury.Other factors include:decreased growth factor secretion,cytokine disturbance,altered keratinocyte proliferation and migration function,decreased fibroblast and myofibroblast proliferation and decreased ability to synthesize and secrete extracellular matrix,increased metalloproteinase synthesis,inflammatory cell function exception,etc.The treatment of diabetic foot ulcer includes medical treatment,surgical treatment and local ulcer management.Local treatment includes wound dressing change,debridement and drainage,dressing coverage,topical medication,negative pressure drainage,etc.,but the effect is not very effective.Photobiomodulation and photodynamic therapy are two methods of phototherapy that promote wound healing.Photobiomodulation is a non-invasive and painless treatment method that directly irradiates the target tissue through a laser or LED device to promote ulcer healing and reduce pain.Photodynamic therapy is also a non-invasive method.After systemic or local administration of photosensitizers,light of a wavelength matching the absorption of the photosensitizers is used to irradiate the target tissues loaded with photosensitizers to produce the desired effects,thereby achieving therapeutic effects.Light modulation and photodynamic energy play a role in promoting wound healing,and with different treatment parameters,they may have different effects on wound healing,collagen deposition,angiogenesis,inflammatory cell infiltration,growth factors,and inflammatory factors.Therefore,in order to explore the effect of the two treatment modalities on the healing of diabetic ulcers at different applied doses,we designed this experiment.Method:(1)Diabetic rat models were constructed,and on this basis,a non-infectious wound models and a Staphylococcus aureus infectious wound models were constructed;(2)Compare the healing rate of non-infected wounds in normoglycemic rats/diabetic rats and those of non-infected wounds in diabetic rats/infected wounds in diabetic rats to verify whether the wound model achieves the expected effect;(3)To study the effect of different doses of LED red light(12/24/48/96 J/cm~2)on the healing rate of non-infected acute wounds on the back of typeⅠdiabetic rats;(4)To study the effect of different concentrations of ALA-PDT(2.5%/5.0%/10%/20%)on the healing rate of non-infectious acute wounds on the back of typeⅠdiabetic rats;(5)To compare the effects of different doses of LED red light and ALA-PDT on the healing rate of non-infectious wounds on typeⅠdiabetic rats;(6)To study the effect of different doses of LED red light(12/24/48/96 J/cm~2)on the healing rate of acute wounds on the back of typeⅠdiabetic rats;(7)To study the effect of different concentrations of ALA-PDT(2.5%/5%/10%/20%)on the healing rate of acute wounds on the back of typeⅠdiabetic rats;(8)To compare the effects of different doses of LED red light and ALA-PDT on the healing rate of back infectious wounds on typeⅠdiabetic rats;(9)To study the effects of ALA-PDT,LED red light and control group on the bacterial load,collagen deposition and macrophage infiltration at the wound sites on the back of typeⅠdiabetic rat infected wounds.Result:(1)The wound healing speed of normoglycemic rats was faster than that of diabetic rats,and the healing speed of non-infectious wounds of diabetic rats was faster than that of infected wounds.(2)Under the energy density set in this experiment,LED red light could promote the healing of non-infectious wounds in T1DM rats.The effect was better at 24J/cm2 and 48J/cm2.Increasing or decreasing ALA concentration reduced the promoting effect;(3)At the ALA concentration set in this experiment,ALA-PDT could promote the healing of non-infectious wounds in T1DM rats,with 2.5%and 5%being better.Increasing the ALA concentration reduced the promoting effect;(4)Compared with ALA-PDT,LED red light has no significant difference in promoting the healing of non-infectious wounds in T1DM rats;(5)Under the energy density set in this experiment,LED red light has no obvious effect on the infectious wounds of T1DM rats;(6)At the ALA concentration set in this experiment,ALA-PDT could promote the healing of infectious wounds in T1DM rats,with 5%and 10%being better.Increasing or decreasing ALA concentration reduced the promoting effect;(7)In the back infection wounds of type 1 diabetic rats,the culture count of Staphylococcus aureus in the wound site after 10%ALA-PDT treatment was significantly decreased on the 3rd,7th and 10th days,and the collagen deposition was significantly increased on the 10th and 14th days,the phagocytic infiltration was significantly reduced on the 10th and14th days.All the above three indicators were statistically different.Conclusion:(1)Compared with normal rats,T1DM rats had delayed wound healing;T1DM rat infected wounds healed slower than non-infected wounds;the model was successfully established in this experiment,and the model was stable;(2)Both LED red light and ALA-PDT could promote the healing of non-infectious wounds on the back of T1DM rats,and there was no significant difference in the effect between the two at the end of the observation;(3)PDT could promote the healing of back infectious wounds in T1DM rats,while LED could not promote the healing of back infectious wounds in T1DM rats;(4)Part of the mechanisms by which ALA-PDT promotes the healing of back infectious wounds in T1DM rats are:reducing wound bacterial load,promoting collagen production,and improving inflammatory response.