The Functional And Mechanical Studies Of Platelet-derived Growth Factor-D In Rat Traumatic Brain Injury

ObjectiveAt present,the function and mechanism of platelet-derived growth factor-D(PDGF-D)in traumatic brain injury(TBI)have not been reported.In this project,we constructed the TBI model in rats,and we aimed to explore the dynamic expression of PDGF-D in TBI models.We also want to further study the role and mechanism of PDGF-D in brain injury after TBI,so as to provide some theoretical guidance for selecting therapeutic target and intervention time after TBI.Methods(1)To evaluate the dynamic expression and function of PDGF-D in TBI by constructing the TBI model in rats.(2)Western blot was carried out to evaluate the expression of PDGF-D,p-PDGFR-?,p-p65 and NF-?B p65 in brain tissues.(3)The tissue immunofluorescence was carried out to analyze the expression of PDGF-D and p-PDGFR-? in cerebral vessels.(4)The quantitative real-time PCR(qRT-PCR)was performed to detect the expression of PDGF-D in brain tissues.(5)Garcia Test was used to evaluate the effect of PDGF-D silence on nerve function of TBI rats.(6)The brain water content was measured to evaluate the effect of PDGF-D silence on brain edema in TBI rats.(7)Enzyme-linked immunosorbent assay(ELISA)was used to detect the expression of inflammatory factors in brain tissues.Results(1)The expression levels of PDGF-D and p-PDGFR-? after TBI were detected by Western blot.The PDGF-D level was increased(p<0.05)6 hours after TBI and remained at the high level until 3 days(p<0.05).The p-PDGFR-? level was increased(p<0.05)12 hours after TBI and remained at the high level until 3 days(p<0.05).(2)PDGF-D and p-PDGFR-? in brain tissues were found by immunofluorescence in the perihematoma area 24 hours after TBI.(3)Silencing PDGF-D improved the nerve function of TBI rats and reduced brain edema.(4)It was found by ELISA that PDGF-D silence could inhibit the expression of inflammatory factors after TBI.(5)Western blot analysis showed that silencing PDGF-D inhibited the expression of p-PDGFR-? and the activation of NF-?B signaling pathway in TBI rats.ConclusionThis study revealed the expression phenomenon of PDGF-D and p-PDGFR-? after TBI in rats,suggesting that PDGF-D and p-PDGFR-? were highly expressed in TBI rats.Moreover,it was found that PDGF-D silence could improve the neurological function,reduce brain edema and inhibit the expression of inflammatory factors in TBI rats.Further mechanism studies showed that PDGF-D silence inhibited the expression of p-PDGFR-?and suppressed the activation of NF-?B signaling pathway in TBI rats.These results suggested that PDGF-D may regulate the activation of NF-?B signaling pathway by activating its receptor PDGFR-?,and then affected the expression of inflammatory factors,so as to participate in the process of secondary brain injury after TBI,which may provide a theoretical basis for selecting therapeutic target and intervention time after TBI.